Fact-checked by Grok 2 weeks ago

Nervous system

The nervous system is a highly complex network of specialized cells that coordinates voluntary and involuntary actions, processes sensory information, and regulates essential bodily functions such as movement, cognition, and homeostasis in animals, particularly vertebrates.^[1] It is divided into two main parts: the central nervous system (CNS), comprising the brain and spinal cord, which serves as the primary processing center, and the peripheral nervous system (PNS), consisting of nerves and ganglia that connect the CNS to the rest of the body, including muscles, organs, and sensory receptors.^[2] This intricate system enables rapid communication through electrical and chemical signals, allowing organisms to respond to internal and external stimuli effectively.^[3] The CNS is protected by the skull and vertebral column and includes the brain, which contains approximately 86 billion neurons organized into structures like the cerebrum (divided into two hemispheres and four lobes: frontal, parietal, occipital, and temporal) responsible for higher functions such as thinking, memory, and voluntary movement, and the spinal cord, which extends from the brainstem to the lower back (typically ending at the L1-L2 level) and relays signals between the brain and body while coordinating reflexes.^[2]^[4] The brain's gray matter, rich in neuron cell bodies, handles integration and processing, while white matter facilitates signal transmission via myelinated axons.^[2] Embryologically, the CNS originates from the neural tube formed around the third week of gestation, differentiating into brain vesicles that develop into mature structures like the cerebrum from the telencephalon.^[2] In contrast, the PNS encompasses all neural elements outside the CNS, including 31 pairs of spinal nerves (emerging from the spinal cord's 31 segments: 8 cervical, 12 thoracic, 5 lumbar, 5 sacral, and 1 coccygeal) and 12 pairs of cranial nerves that branch to innervate peripheral tissues.^[2] The PNS is further subdivided into the somatic nervous system, which governs voluntary motor control and sensory input from the skin, muscles, and joints, and the autonomic nervous system, which manages involuntary processes like heart rate, digestion, and respiration through its sympathetic (activating "fight-or-flight" responses), parasympathetic (promoting "rest-and-digest" activities), and enteric (controlling gastrointestinal functions) divisions.^[1] At the cellular level, the nervous system's functionality relies on neurons, the primary signaling units with dendrites that receive inputs and axons (some up to 1 meter long) that transmit impulses via action potentials and neurotransmitters, and supportive glial cells such as astrocytes (which provide structural support and nutrient delivery), oligodendrocytes (which produce myelin sheaths for faster signal conduction in the CNS), and microglia (which act as immune defenders).^[1] Neurons integrate sensory data—such as touch, pain, or visual cues—process it in the CNS, and generate appropriate motor or autonomic outputs, ensuring adaptive responses to environmental changes like increased sweating during heat or accelerated heartbeat during stress.^[3] This coordinated signaling underpins complex behaviors, learning, and survival mechanisms across species.^[1]

Structure

Neurons

Neurons are the fundamental excitable cells of the nervous system, specialized for the rapid transmission of electrical and chemical signals to enable communication across the body.^[5] These cells integrate sensory inputs, process information, and generate motor outputs, forming the basis of nervous system function through coordinated signaling.^[5] Unlike other cells, neurons exhibit unique electrical excitability due to specialized membrane properties that allow for the generation and propagation of action potentials.^[6] The morphology of a typical neuron includes the cell body, or soma, which houses the nucleus and organelles essential for protein synthesis and cellular maintenance.^[5] Extending from the soma are dendrites, branched structures that receive synaptic inputs from other neurons, increasing the surface area for signal integration.^[7] The axon arises from the axon hillock, a specialized region near the soma that initiates action potentials, and extends as a long projection for transmitting signals to distant targets; in myelinated axons, the myelin sheath—formed by glial cells—insulates the axon to enhance conduction speed via saltatory propagation.^[7] At the axon's end, synaptic terminals release neurotransmitters to communicate with downstream cells.^[7] Neurons are classified structurally into unipolar (one process), bipolar (two processes), and multipolar (multiple processes) types, with multipolar being the most common in the vertebrate central nervous system.^[5] Functionally, they divide into sensory neurons (transmitting afferent signals from periphery to central nervous system), motor neurons (carrying efferent signals to effectors like muscles), and interneurons (facilitating local processing and integration within the nervous system).^[8] By neurotransmitter, examples include cholinergic neurons that release acetylcholine for excitatory or inhibitory effects at neuromuscular junctions and adrenergic neurons that release norepinephrine for sympathetic responses. Glial cells provide essential support by maintaining the ionic environment around neurons to sustain excitability. The excitability of neurons arises from voltage-gated ion channels in the plasma membrane, which regulate the flow of ions like sodium (Na⁺) and potassium (K⁺) to establish a resting membrane potential of approximately -70 mV.^[6] Action potentials are triggered when depolarization reaches threshold at the axon hillock, leading to rapid Na⁺ influx followed by K⁺ efflux for repolarization.^[9] The equilibrium potential for an ion, which drives these fluxes, is described by the Nernst equation; for potassium, it is given by

E_K = \frac{RT}{zF} \ln \left( \frac{[K^+]_o}{[K^+]_i} \right)

where R is the gas constant, T is temperature, z is the ion's valence, F is Faraday's constant, and [K^+]_o and [K^+]_i are extracellular and intracellular concentrations, respectively—typically yielding E_K \approx -90 mV in neurons.^[10] The Hodgkin-Huxley model, developed from squid axon experiments, mathematically describes action potential generation through time-dependent conductances for Na⁺ and K⁺ channels, expressed as a system of differential equations for membrane potential V and gating variables.^[11] Representative examples include pyramidal neurons in the cerebral cortex, which are multipolar excitatory cells with a prominent apical dendrite and extensive basal dendrites, enabling integration of inputs for higher cognitive functions like decision-making.^[12] In the cerebellum, Purkinje cells feature highly branched dendritic arbors that receive massive parallel fiber inputs, serving as inhibitory output neurons crucial for motor coordination and error correction.^[13]

Glial cells

Glial cells, also known as neuroglia, are non-neuronal cells that constitute a significant portion of the nervous system, providing essential structural, metabolic, and immune support to neurons.^[14] In the human brain, there are approximately 86 billion neurons and 40–50 billion glial cells, resulting in a glia-to-neuron ratio of approximately 0.5:1 overall, though this ratio varies by region; for instance, in the cerebral cortex, the glia-to-neuron ratio is about 3.7:1.^[15]^[16] These cells do not generate action potentials but play critical roles in maintaining the neural environment, including ion homeostasis through interactions with neuronal ion channels.^[17] Glial cells are classified into several types, each with specialized functions. Astrocytes, star-shaped cells abundant in the central nervous system (CNS), maintain the blood-brain barrier by forming end-feet processes around blood vessels, supply nutrients to neurons via glucose transport, and modulate synaptic activity by regulating neurotransmitter levels and calcium signaling.^[17] Oligodendrocytes in the CNS and Schwann cells in the peripheral nervous system (PNS) produce myelin sheaths that insulate axons, enabling saltatory conduction and increasing conduction velocity by up to 100-fold at nodes of Ranvier, the gaps between myelin segments where action potentials are regenerated.^[14] Microglia, the resident immune cells of the CNS, perform phagocytosis to clear debris and pathogens, and conduct immune surveillance by monitoring the neural parenchyma for signs of injury or infection.^[17] Ependymal cells line the ventricles of the brain and the central canal of the spinal cord, contributing to the production and circulation of cerebrospinal fluid (CSF) through ciliated surfaces that facilitate fluid flow.^[18] In response to injury or disease, glial cells contribute to neuroinflammation; for example, activated microglia release pro-inflammatory cytokines such as interleukin-1 (IL-1), IL-6, and tumor necrosis factor-alpha (TNF-α), which can amplify immune responses but may also lead to chronic inflammation if unregulated.^[19] A key concept in glial function is the tripartite synapse, where astrocytes actively participate in synaptic transmission by sensing neurotransmitters via receptors, releasing gliotransmitters like glutamate and ATP, and thereby modulating neuronal communication and synaptic plasticity.^[20] Evolutionarily, glial diversity has increased from invertebrates, where simpler glial types like sheath glia provide basic support, to vertebrates, which exhibit more specialized subtypes such as astrocytes and oligodendrocytes adapted for complex neural processing.^[21]

Vertebrate anatomy

The vertebrate nervous system is divided into the central nervous system (CNS), consisting of the brain and spinal cord, and the peripheral nervous system (PNS), which includes nerves and ganglia outside the CNS.^[2] This organization allows for centralized processing in the CNS and distributed communication via the PNS.^[22] The brain, the largest component of the CNS, is subdivided into the forebrain, midbrain, and hindbrain. The forebrain encompasses the cerebrum (divided into frontal, parietal, occipital, and temporal lobes), basal nuclei, thalamus, and hypothalamus, handling higher cognitive functions and sensory integration.^[2] The midbrain, part of the brainstem, serves as a relay for auditory and visual signals.^[2] The hindbrain includes the pons and medulla oblongata (in the brainstem) for vital functions like breathing and heart rate, as well as the cerebellum with its anterior, posterior, and flocculonodular lobes for motor coordination.^[2] In humans, the brain has a mass of approximately 1.3–1.4 kg.^[23] The spinal cord, extending from the foramen magnum to the L1–L2 vertebral level, measures about 45 cm in length in adults and is segmented into cervical, thoracic, lumbar, and sacral regions corresponding to 31 pairs of spinal nerves.^[2] It consists of central gray matter, containing neuronal cell bodies and dendrites in dorsal (sensory) and ventral (motor) horns, surrounded by white matter composed of myelinated axons forming ascending and descending tracts.^[2]^[22] Neurons and glial cells integrate to form these structures; for instance, the corticospinal tract is a major white matter bundle of myelinated axons originating from the motor cortex and descending through the brainstem and spinal cord to synapse with motor neurons in the ventral horn, enabling voluntary movement.^[24] Nuclei, clusters of neuronal cell bodies, are prominent in gray matter regions like the spinal cord's horns and brainstem.^[22] The CNS is protected by three meninges: the outermost dura mater (tough fibrous layer), the middle arachnoid mater (web-like with subarachnoid space), and the innermost pia mater (adhering to the surface).^[2] The brain's ventricles—lateral, third, and fourth—along with central spinal canal, contain cerebrospinal fluid (CSF) produced by choroid plexuses, which circulates to cushion and nourish the CNS.^[2] The blood-brain barrier, formed by endothelial cells with tight junctions, pericytes, basement membrane, and astrocyte end-feet, selectively regulates substance passage from blood to brain tissue.^[25] The PNS comprises the somatic nervous system, which innervates skeletal muscles and skin via sensory (afferent) and motor (efferent) fibers, and the autonomic nervous system, controlling involuntary functions.^[26]^[27] The autonomic division includes the sympathetic system (thoracolumbar outflow, promoting "fight or flight" responses like increased heart rate) and parasympathetic system (craniosacral outflow, fostering "rest and digest" activities like slowing heart rate), balanced for homeostasis.^[27] The enteric nervous system, a semi-autonomous network in the gastrointestinal tract with more neurons than the spinal cord, regulates digestion independently but modulates via autonomic inputs.^[27] Peripheral nerves include 12 pairs of cranial nerves emerging from the brain (e.g., olfactory for smell, optic for vision, vagus for visceral control) and 31 pairs of spinal nerves (8 cervical, 12 thoracic, 5 lumbar, 5 sacral, 1 coccygeal), which are mixed sensory-motor and attach via dorsal (sensory) and ventral (motor) roots.^[26]^[2] These nerves form the communication network between the CNS and periphery.^[26]

Comparative anatomy and evolution

The evolution of the nervous system traces back to the earliest metazoans, where precursors to neural signaling appear in sponges (Porifera), which lack true neurons but possess choanocytes capable of intercellular signaling via calcium waves and chemical mediators, enabling coordinated cellular responses without a centralized network.^[28] In contrast, cnidarians (such as jellyfish in the Radiata clade) represent the first appearance of a true nervous system in the form of a diffuse nerve net, consisting of interconnected ectodermal and endodermal neuronal networks that facilitate basic sensory-motor integration without centralization, marking a key innovation around 600 million years ago.^[29]^[30] This decentralized architecture underscores the basal eumetazoan condition, where neural elements evolved independently of bilaterian centralization.^[31] With the emergence of Bilateria, nervous systems underwent significant centralization, featuring ventral nerve cords and ganglia that supported more complex behaviors. In annelids and nematodes, the ventral nerve cord serves as a longitudinal chain of segmental ganglia, coordinating locomotion and sensory processing along the body axis, a configuration hypothesized to reflect the urbilaterian ancestor.^[32] Arthropods advanced this further with a prominent brain (supraesophageal ganglion) and segmented ventral nerve chain, including specialized structures like the mushroom bodies in insects, which are neuropils dedicated to olfactory learning and memory.^[33] Molluscan nervous systems exhibit remarkable diversity, culminating in cephalopods such as the octopus, which possess a distributed brain comprising over 500 million neurons organized into lobes for advanced vision, manipulation, and arm-specific processing, rivaling vertebrate complexity despite convergent evolution.^[34]^[35] In the vertebrate lineage, nervous system evolution built upon the simple dorsal hollow nerve cord of early chordates, progressively expanding into a centralized central nervous system with the telencephalon undergoing marked elaboration in mammals to support higher cognition.^[36] Key evolutionary principles include the concept of "identified" neurons—individually recognizable, invariant cells in invertebrates like Aplysia californica, which have facilitated detailed studies of behaviorally relevant circuits, such as those underlying gill withdrawal reflexes.^[37] Allometric scaling governs brain size relative to body complexity, with neural tissue typically increasing as body mass raised to approximately 0.75, reflecting metabolic constraints and adaptive pressures across metazoans.^[38] The nematode Caenorhabditis elegans exemplifies minimal complexity, with its entire nervous system comprising exactly 302 neurons whose full connectome has been mapped, providing a foundational model for neural wiring.^[39] Underlying this diversity is the deep conservation of ion channels, such as voltage-gated sodium and potassium types, which originated at the metazoan base and enable action potential generation across phyla.^[40]^[41]

Development

Embryonic development

The embryonic development of the nervous system in vertebrates begins with neural induction, a process where signals from the dorsal mesoderm, known as the Spemann-Mangold organizer, direct overlying ectodermal cells to form the neural plate instead of epidermis. In the landmark 1924 experiment by Hans Spemann and Hilde Mangold using newt embryos, transplantation of the dorsal blastopore lip induced a secondary neural axis in host embryos, demonstrating the organizer's inductive capacity.^[42] Subsequent molecular studies revealed that organizer-derived proteins such as noggin and chordin inhibit bone morphogenetic protein (BMP) signaling in the ectoderm, thereby promoting neural fate.^[42] Following induction, neurulation shapes the neural plate into the neural tube, the precursor to the central nervous system (CNS). During primary neurulation, which occurs in the third week of human embryogenesis, the neural plate thickens and folds along its midline to form the neural groove, with the neural folds elevating and fusing to create a hollow neural tube.^[43] Neural crest cells, arising at the junction of the neural folds and ectoderm, delaminate and migrate to form peripheral nervous system (PNS) components, including sensory and autonomic neurons, as well as glia such as Schwann cells.^[43] Secondary neurulation then completes the caudal neural tube through mesenchymal cavitation, ensuring continuity of the spinal cord.^[43] Regionalization of the neural tube establishes distinct domains along the anteroposterior and dorsoventral axes through morphogen gradients and transcription factors. Hox genes, expressed in nested patterns along the anteroposterior axis, specify segmental identities, such as rhombomeres in the hindbrain and spinal cord regions, with their activation mediated by caudal factors like CDX and retinoic acid.^[44] Ventrally, Sonic hedgehog (Shh), secreted from the notochord and floor plate, patterns cell fates via concentration-dependent Gli transcription factors, inducing motor neurons and interneurons.^[44] Dorsally, Wnt signaling from the roof plate promotes sensory neuron progenitors and antagonizes Shh, contributing to the binary dorsoventral organization.^[45] These signals culminate in the formation of three primary brain vesicles by the end of the fourth week: the prosencephalon (forebrain), mesencephalon (midbrain), and rhombencephalon (hindbrain).^[44] In humans, key milestones include neural tube closure by the fourth week, with the anterior neuropore sealing around day 25 and the posterior neuropore by day 28, marking the transition from open neural folds to a closed tube.^[43] Brain flexures emerge concurrently, including the cephalic flexure at the midbrain level and cervical flexure at the hindbrain-spinal cord junction, which accommodate rapid growth and position the forebrain rostrally. Cell proliferation during this phase is driven by neural stem cells in the ventricular zone, expanding the neuroepithelium.^[43] Failure of neural tube closure leads to defects such as anencephaly, where the anterior neuropore remains open, resulting in absence of the forebrain and calvaria, and spina bifida, involving incomplete posterior closure and exposure of the spinal cord.^[46] These conditions arise primarily from multifactorial causes, including folate deficiency, and affect approximately 1 in 2,875 U.S. births for spina bifida and about 1 in 5,100 for anencephaly annually (as of 2023 data).^[46]^[47]^[48] Neurulation is evolutionarily conserved across chordates, with the neural plate invagination process evident in cephalochordates like amphioxus, underscoring its ancient origin in the common ancestor.^[49] Neurogenesis proceeds through a coordinated sequence of proliferation, differentiation, and migration orchestrated by neural stem cells, initially as neuroepithelial cells transitioning to radial glia. Radial glia undergo symmetric divisions to expand the progenitor pool in the ventricular zone, followed by asymmetric divisions generating intermediate progenitors or neuroblasts that commit to neuronal fates.^[50] Differentiating neurons then migrate along radial glial scaffolds toward the cortical plate, establishing laminar organization via somal translocation or locomotion, with proliferation ceasing as gliogenesis predominates later in embryogenesis.^[50]

Post-embryonic development and plasticity

Post-embryonic development of the nervous system involves dynamic processes that refine neural circuits in response to experience, extending from infancy through adulthood. Following the initial surge of synaptogenesis during early postnatal periods, where synapse density peaks in the human cerebral cortex around 3-5 years of age, the brain undergoes extensive refinement.^[51] Synaptic pruning, which eliminates unused connections, intensifies during adolescence, reducing up to 40% of synapses to streamline efficient neural pathways.^[52] Concurrently, myelination of axons, which enhances signal conduction speed, progresses into early adulthood, particularly in prefrontal regions, supporting cognitive maturation.^[53] Adult neurogenesis, the generation of new neurons, persists in select mammalian brain regions postnatally, including the subgranular zone of the hippocampus and the subventricular zone.^[54] In the hippocampus, these newborn neurons integrate into circuits involved in learning and memory, while subventricular zone-derived cells primarily contribute to olfactory bulb replenishment.^[55] Brain-derived neurotrophic factor (BDNF), a key growth factor, promotes survival and differentiation of these progenitors, modulating neurogenesis in response to environmental stimuli.^[56] Neural plasticity mechanisms underpin experience-dependent adaptations throughout life, with long-term potentiation (LTP) strengthening synapses through repeated activity and long-term depression (LTD) weakening them to refine connectivity.^[57] These processes align with the Hebbian learning rule, often summarized as "cells that fire together wire together," where correlated presynaptic and postsynaptic activity drives synaptic changes.^[58] Critical periods exemplify heightened plasticity early in life; for instance, monocular visual deprivation in kittens during a brief postnatal window irreversibly shifts ocular dominance in visual cortex, as demonstrated in foundational experiments.^[59] Environmental enrichment further illustrates plasticity, increasing cortical thickness in rodents through enhanced synaptic density and dendritic arborization.^[60] As aging progresses, neural plasticity gradually declines, with reduced LTP induction and slower dendritic remodeling contributing to cognitive impairments.^[61] However, compensatory mechanisms persist, such as exercise-induced upregulation of BDNF and hippocampal neurogenesis, which mitigate age-related losses and support functional recovery.^[62] Structural plasticity, including dendritic spine remodeling—where spines form, stabilize, or retract in response to activity—facilitates circuit adaptation, notably after brain injury, enabling functional reorganization in surviving networks.^[63] This post-injury spine turnover, observed via in vivo imaging, correlates with behavioral improvements in motor and sensory domains.^[64]

Function

Neuronal signaling and synapses

Neurons communicate through electrical and chemical signals, with action potentials serving as the primary mechanism for propagating information along axons. The resting membrane potential of a neuron is typically around -70 mV, maintained by the unequal distribution of ions across the lipid bilayer and the selective permeability of the membrane, primarily to potassium ions.^[65] This potential can be described by the Goldman-Hodgkin-Katz (GHK) equation, which accounts for the contributions of multiple ions:

V_m = \frac{RT}{F} \ln \left( \frac{P_K [K^+]_o + P_{Na} [Na^+]_o + P_{Cl} [Cl^-]_i}{P_K [K^+]_i + P_{Na} [Na^+]_i + P_{Cl} [Cl^-]_o} \right)

where V_m is the membrane potential, R is the gas constant, T is temperature, F is Faraday's constant, P denotes permeability, and subscripts i and o indicate intracellular and extracellular concentrations, respectively. When a neuron receives sufficient excitatory input, the membrane depolarizes to a threshold (around -55 mV), triggering an action potential via the opening of voltage-gated sodium channels, allowing Na⁺ influx that rapidly drives the potential toward +40 mV. This is followed by repolarization through sodium channel inactivation and potassium channel opening, leading to K⁺ efflux that restores the negative potential. Action potentials adhere to the all-or-none principle: once initiated, they propagate with fixed amplitude and duration, independent of stimulus strength, ensuring reliable signal transmission over long distances.^[65] At synapses, action potentials trigger the release of signaling molecules to convey information to the postsynaptic neuron. Synaptic transmission occurs via two main types: chemical and electrical. In chemical synapses, the arriving action potential opens voltage-gated calcium channels in the presynaptic terminal, causing Ca²⁺ influx that promotes the fusion of synaptic vesicles with the presynaptic membrane through proteins like SNARE complexes.^[66] This exocytosis releases neurotransmitters into the synaptic cleft, where they diffuse to bind postsynaptic receptors.^[66] Electrical synapses, in contrast, enable direct ion flow between neurons via gap junctions formed by connexin proteins, allowing rapid, bidirectional transmission without chemical intermediaries, though they are less common in vertebrate central nervous systems.^[67] Neurotransmitter binding generates postsynaptic potentials that modulate the postsynaptic membrane potential. Excitatory postsynaptic potentials (EPSPs) depolarize the membrane, typically through Na⁺ or Ca²⁺ influx via ionotropic receptors, increasing the likelihood of reaching action potential threshold.^[68] Inhibitory postsynaptic potentials (IPSPs), conversely, hyperpolarize the membrane, often via Cl⁻ influx or K⁺ efflux, reducing excitability.^[68] These graded potentials summate temporally and spatially at the postsynaptic site, with integration governed by the membrane time constant \tau = R_m C_m, where R_m is membrane resistance and C_m is capacitance; longer \tau values allow greater temporal summation of inputs.^[69] Major neurotransmitter classes include amino acids, monoamines, and peptides. Amino acids like glutamate (excitatory) and GABA (inhibitory) act rapidly; glutamate binds ionotropic receptors (e.g., AMPA, NMDA) to open cation channels, while GABA targets GABAA receptors for Cl⁻ conductance.^[70] Monoamines such as dopamine and serotonin modulate slower via metabotropic G-protein-coupled receptors, influencing second-messenger pathways.^[70] Neuropeptides, like substance P, typically act on metabotropic receptors for prolonged effects.^[71] Ionotropic receptors directly gate ion channels for fast synaptic responses, whereas metabotropic receptors indirectly alter excitability through intracellular signaling.^[72] Neurotransmitter release follows quantal principles, where each vesicle represents a quantum of transmitter; spontaneous miniature EPSPs (mEPSPs) reflect single-vesicle release, with evoked responses comprising multiples of these quanta. After release, neurotransmitters are cleared from the cleft to terminate signaling, primarily via reuptake into presynaptic terminals or glia through transporter proteins (e.g., SERT for serotonin) or enzymatic degradation (e.g., acetylcholinesterase for acetylcholine).^[73] These mechanisms recycle or inactivate transmitters, preventing prolonged receptor activation.^[73]

Neural circuits and systems

Neural circuits are organized networks of interconnected neurons that process sensory information, integrate signals, and generate coordinated outputs to drive behavior and physiological responses. These circuits form the functional units of the nervous system, enabling everything from simple reflexes to complex cognitive processes through patterned activity across populations of neurons. In vertebrates, circuits exhibit modular architectures that allow for efficient information flow, with basic building blocks like synapses linking individual neurons into larger ensembles that can be tuned for specific tasks. Common circuit types include feedforward and feedback loops, which dictate the direction and recurrence of signal propagation. Feedforward loops enable unidirectional information flow, such as in sensory processing where excitatory inputs propagate across layers without immediate recurrence, facilitating rapid transmission.^[74] Feedback loops, in contrast, incorporate recurrent connections that refine or modulate outputs, often through inhibitory interneurons that prevent overexcitation and stabilize activity.^[75] Convergent patterns integrate multiple inputs onto a single neuron or output, enhancing signal detection by summing diverse sources, while divergent patterns distribute a single input to multiple targets, amplifying or broadcasting signals for broader influence.^[74] Local projections confine interactions within a brain region or spinal segment, supporting fine-tuned processing, whereas long-range projections connect distant areas, such as cortico-thalamic pathways, to coordinate global functions like attention or movement.^[76] Reflex arcs represent fundamental circuit motifs for rapid, involuntary responses mediated by the spinal cord. Monosynaptic arcs involve a direct connection between a sensory neuron and a motor neuron, exemplified by the knee-jerk reflex, where stretching the quadriceps tendon activates muscle spindles, leading to immediate contraction via lumbar segments L2-L4 without interneuron involvement.^[77] Polysynaptic arcs incorporate interneurons for more complex coordination, as in the withdrawal reflex, where nociceptive input from the skin triggers flexor muscle contraction and extensor inhibition through dorsal horn interneurons, protecting the body from harm.^[78] These arcs operate independently of higher brain centers, ensuring swift action while integrating briefly with sensory inputs for precision. Central pattern generators (CPGs) are endogenous neural circuits that produce rhythmic motor outputs without external rhythmic cues, underlying behaviors like locomotion and breathing. In the lamprey, spinal CPGs generate alternating bursts for undulatory swimming, driven by glutamatergic and glycinergic interactions among interneurons and motor neurons.00581-4) For breathing, medullary CPGs in mammals orchestrate respiratory rhythms via interconnected pre-Bötzinger and retrotrapezoid nucleus neurons, modulated by chemosensory feedback.^[79] These oscillators rely on reciprocal inhibition and intrinsic bursting properties to sustain cycles. Specific vertebrate circuits illustrate advanced organization. Basal ganglia loops process motor planning through direct and indirect pathways: the direct pathway disinhibits the thalamus to facilitate selected movements, while the indirect pathway suppresses competitors via subthalamic nucleus excitation, enabling adaptive action selection.^[80] In the hippocampus, theta rhythms (4-8 Hz) emerge from circuit interactions between pyramidal cells, interneurons, and entorhinal inputs, synchronizing neuronal firing to support spatial navigation and memory encoding.^[81] Key concepts in circuit function include convergence, where multiple afferents summate to sharpen outputs, and divergence, where one input fans out to recruit ensembles, both optimizing information processing.^[82] Homeostasis maintains circuit tuning by scaling synaptic strengths and intrinsic excitability, ensuring stable firing rates and network balance despite perturbations, as seen in cortical adaptations over days.^[83] Evolutionarily, simpler circuits appear in invertebrates; for instance, crayfish escape responses rely on giant fiber systems, where sensory stimuli activate medial or lateral giants to trigger rapid tail-flips via electrical synapses, providing a foundational model for studying circuit stereotypy.^[84]

Sensory-motor integration

Sensory systems process various modalities of information from the environment and the body, relaying signals through primary afferents to the cerebral cortex via thalamic nuclei. The somatosensory system handles touch, pressure, pain, temperature, and proprioception, with sensory receptors in the skin, muscles, and joints sending signals through ascending pathways to the primary somatosensory cortex (S1). Visual information is transduced by photoreceptors in the retina and relayed via the lateral geniculate nucleus to the primary visual cortex (V1), while auditory signals from hair cells in the cochlea pass through the cochlear nucleus and inferior colliculus to the primary auditory cortex (A1). These pathways ensure that sensory data is organized topographically for precise perception.^[85]^[86]^[87] A key example of sensory relay is the dorsal column-medial lemniscus (DCML) pathway, which transmits fine touch, vibration, and proprioception from mechanoreceptors in the periphery. First-order neurons ascend ipsilaterally in the dorsal columns of the spinal cord to the medulla, where second-order neurons decussate and project via the medial lemniscus to the ventral posterolateral nucleus of the thalamus, ultimately reaching S1. This pathway enables discriminative touch and conscious proprioception essential for coordinated movement.^[88]^[89] Motor systems exhibit hierarchical control, integrating reflexive responses at the spinal level with higher-order planning in the cortex to generate voluntary actions. Spinal reflexes, such as the knee-jerk response, involve local circuits that bypass the brain for rapid, automatic adjustments. Brainstem and basal ganglia contribute to posture and automatic movements via extrapyramidal tracts, including the rubrospinal and vestibulospinal pathways, which modulate muscle tone and balance. At the apex, the primary motor cortex (M1) and premotor areas orchestrate complex sequences through the pyramidal tract, primarily the corticospinal tract, which decussates in the medulla to directly influence lower motor neurons for skilled, voluntary movements.^[90]^[91]^[92] Efferent pathways thus form a descending hierarchy: pyramidal tracts for fine, fractionated control of distal muscles, and extrapyramidal for proximal stability and synergy. This organization allows seamless transitions from instinctive reflexes to intentional behaviors, with feedback loops refining output.^[93]^[94] Sensory-motor integration occurs through closed-loop mechanisms that combine afferent input with efferent commands to adapt and refine actions in real time. Sensorimotor loops, particularly involving the cerebellum, detect discrepancies between predicted and actual sensory outcomes, enabling error correction during movement. For instance, the cerebellum receives sensory feedback via mossy and climbing fibers and compares it to internal models of motor commands, adjusting outputs to minimize errors in timing and coordination.^[95] Mirror neurons exemplify social aspects of integration, firing both during action execution and observation of similar actions in others. Discovered in the 1990s by Giacomo Rizzolatti's team in the premotor cortex of macaque monkeys, these neurons activate in area F5 when grasping objects or observing others grasp, facilitating action understanding and imitation. In humans, analogous activity in the inferior frontal gyrus and premotor cortex supports empathy by simulating observed emotions and intentions.^[96] Proprioception, mediated by muscle spindles, provides critical feedback on limb position and velocity for smooth motor control. These intrafusal fibers detect stretch via Ia and II afferents, relaying signals to the spinal cord and cortex to prevent overextension and guide precise movements. The vestibulo-ocular reflex (VOR) stabilizes gaze during head turns by coordinating vestibular input with ocular motor nuclei, generating compensatory eye movements opposite to head velocity through direct brainstem pathways.^[97]^[98] A core principle of this integration is predictive coding in sensorimotor regions, where the brain anticipates sensory consequences of actions to optimize processing. In the motor cortex, forward models generate predictions that suppress expected reafferent signals, allowing efficient detection of novel errors and rapid adaptation. This mechanism underpins anticipatory adjustments, as seen in cerebellar circuits, enhancing overall behavioral efficiency.^[99]^[95]

Pathology

Developmental and congenital disorders

Developmental and congenital disorders of the nervous system arise from disruptions during embryonic or fetal stages, leading to structural or functional abnormalities that persist into infancy and beyond. These conditions often stem from genetic mutations, environmental teratogens, or multifactorial interactions that interfere with critical processes like neural tube closure, progenitor proliferation, and synaptic maturation. Unlike acquired pathologies, they manifest early due to prenatal origins, affecting neuronal migration, differentiation, and connectivity. Neural tube defects (NTDs) represent a primary category of congenital malformations, occurring when the neural tube fails to close properly between the third and fourth weeks of gestation. Common forms include spina bifida, characterized by incomplete closure of the spinal neural tube resulting in exposed spinal cord and meninges, and anencephaly, a lethal condition involving absence of the cranial vault and cerebral hemispheres due to failed anterior closure. The incidence of NTDs varies globally but averages about 1 per 1,000 live births in populations without fortification programs. Folate deficiency is a well-established risk factor, as it impairs DNA synthesis and methylation critical for neural tube formation, with maternal supplementation reducing NTD risk by up to 70%. Genetic factors, such as polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene, exacerbate susceptibility by disrupting folate metabolism, particularly when combined with low dietary intake. Prenatal diagnosis relies on ultrasound for initial screening, with magnetic resonance imaging (MRI) providing detailed visualization of spinal cord involvement and associated anomalies to guide management. Neurodevelopmental disorders encompass a spectrum of conditions influenced by genetic and environmental perturbations during brain assembly. Autism spectrum disorder (ASD) arises from imbalances in synaptic pruning and connectivity, where genetic variants affecting neuronal adhesion and signaling—combined with environmental exposures like advanced parental age or prenatal infections—lead to excessive synaptic density and altered social cognition. Synaptic pruning deficits, often linked to microglial dysfunction and impaired autophagy, contribute to the core features of social communication challenges and repetitive behaviors observed in ASD. Intellectual disability, as seen in Down syndrome due to trisomy 21, results from gene dosage effects that disrupt neurogenesis and neuronal proliferation in the developing cortex and hippocampus. The extra chromosome 21 impairs progenitor cell division and migration, leading to reduced brain volume and cognitive deficits, with affected individuals showing delayed milestones in language and motor skills. Congenital malformations further illustrate vulnerabilities in cerebrospinal fluid (CSF) dynamics and brain growth. Hydrocephalus involves accumulation of CSF due to blockage in its flow or absorption pathways, often from congenital aqueductal stenosis or genetic anomalies like L1CAM mutations that narrow ventricular passages. This obstruction, present from birth, causes ventricular enlargement and increased intracranial pressure, potentially compressing surrounding neural tissue. Microcephaly, marked by a head circumference below the third percentile, reflects depleted neural progenitors and cortical thinning; for instance, Zika virus infection targets proliferating neural stem cells, inducing apoptosis and cell-cycle arrest to halt brain expansion. Diagnostic prenatal MRI enhances detection of these malformations by delineating ventricular dilation or cortical layering defects not fully resolved by ultrasound. Teratogens, as exogenous agents crossing the placenta, exemplify environmental contributors to these disorders. Prenatal alcohol exposure induces fetal alcohol syndrome (FAS), featuring cerebellar hypoplasia through direct neurotoxic effects on Purkinje cell precursors and disrupted granule cell migration, resulting in coordination deficits and cognitive impairment. These disruptions highlight how substances like alcohol interfere with embryonic signaling pathways, underscoring the need for preconceptional risk mitigation. Overall, such disorders emphasize the intricate interplay of genetic predispositions and teratogenic insults during vulnerable developmental windows.

Acquired and degenerative disorders

Acquired and degenerative disorders of the nervous system encompass a range of conditions arising from external insults, injuries, infections, or progressive cellular breakdown in mature neural tissues, leading to impaired function, cognitive decline, and motor deficits. These disorders contrast with developmental anomalies by emerging later in life due to environmental exposures, vascular events, or age-related protein accumulation. Globally, neurodegenerative conditions contribute significantly to disease burden, with dementia affecting approximately 57 million people worldwide in 2021, over 60% of whom live in low- and middle-income countries.^[100] Neurodegenerative diseases represent a major subset, characterized by the progressive loss of neurons and synaptic connections, often driven by protein misfolding and aggregation. In Alzheimer's disease (AD), the most common form, extracellular amyloid-beta plaques and intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein accumulate, particularly in the hippocampus, leading to atrophy and memory impairment.^[101] The apolipoprotein E ε4 (APOE4) allele serves as the strongest genetic risk factor for sporadic AD, increasing susceptibility by promoting amyloid aggregation and neuroinflammation, with carriers of one ε4 allele facing a threefold higher risk and two alleles up to a 90% lifetime risk.^[102] In the United States alone, an estimated 7.2 million individuals aged 65 and older live with Alzheimer's dementia in 2025.^[103] Parkinson's disease (PD) involves the degeneration of dopaminergic neurons in the substantia nigra, resulting in dopamine depletion and the formation of intraneuronal Lewy bodies containing alpha-synuclein aggregates, which manifest as bradykinesia, rigidity, and tremor.^[104] Amyotrophic lateral sclerosis (ALS), another motor neuron disease, features the selective degeneration of upper and lower motor neurons in the cortex, brainstem, and spinal cord, leading to muscle weakness and paralysis without sensory involvement.^[105] Across these conditions, neuroinflammation plays a pivotal role in progression, with activated microglia releasing pro-inflammatory cytokines that exacerbate neuronal damage and protein pathology.^[106] Traumatic brain injury (TBI) constitutes a key acquired disorder, often resulting from mechanical forces that cause concussions or more severe diffuse axonal injury (DAI), where shearing disrupts white matter tracts and impairs neural communication.^[107] TBI increases vulnerability to long-term neurodegeneration, including elevated risks for Alzheimer's and Parkinson's. Stroke, a vascular disorder, arises from ischemic blockage or hemorrhagic rupture in cerebral arteries, affecting specific vascular territories such as the middle cerebral artery supplying motor and sensory cortices, leading to focal deficits like hemiparesis or aphasia.^[108] Ischemic strokes account for about 87% of cases, with outcomes influenced by reperfusion therapies. Infectious and immune-mediated disorders further illustrate acquired nervous system pathology. Multiple sclerosis (MS) is an autoimmune condition where autoreactive T-cells infiltrate the central nervous system, causing demyelination of axons in the white matter and resultant conduction delays, manifesting as relapsing-remitting or progressive neurological symptoms.^[109] Encephalitis, often infectious, involves brain parenchymal inflammation; for instance, herpes simplex virus targets the temporal lobe, leading to seizures, memory loss, and potential necrosis if untreated. Prion diseases, such as Creutzfeldt-Jakob disease, exemplify rapid neurodegeneration via infectious protein misfolding, where misfolded prions propagate conformational changes in normal prion protein, causing spongiform encephalopathy and swift cognitive-motor decline.^[110]

References

[1]
In brief: How does the nervous system work? - InformedHealth.org
May 4, 2023 · The nervous system takes in information through our senses, processes the information and triggers reactions, such as making your muscles move or causing you ...What makes up our nervous... · What is the difference between...
[2]
Anatomy, Central Nervous System - StatPearls - NCBI Bookshelf - NIH
Oct 10, 2022 · The nervous system is divided into the central nervous system (CNS) and the peripheral nervous system. The CNS includes the brain and spinal cord.Introduction · Structure and Function · Embryology · Surgical Considerations
[3]
What are the parts of the nervous system? | NICHD
Oct 1, 2018 · The nervous system has two main parts: The nervous system transmits signals between the brain and the rest of the body, including internal organs.
[4]
Neuroanatomy, Neurons - StatPearls - NCBI Bookshelf
Neurons are electrically excitable cells that transmit signals. They have a soma, axon, and dendrites, with dendrites receiving and axons carrying signals.
[5]
Ion Channels and the Electrical Properties of Membranes - NCBI - NIH
They are responsible for the electrical excitability of muscle cells, and they mediate most forms of electrical signaling in the nervous system. A single neuron ...
[6]
Nerve Cells - Neuroscience - NCBI Bookshelf - NIH
The dendrites (together with the cell body) provide the major site for synaptic terminals made by the axonal endings of other nerve cells. The synaptic contact ...Missing: soma | Show results with:soma
[7]
Types of neurons - Queensland Brain Institute
For the spinal cord though, we can say that there are three types of neurons: sensory, motor, and interneurons.
[8]
Neuroanatomy, Neuron Action Potential - StatPearls - NCBI Bookshelf
Neurons are electrically excitable, reacting to input via the production of electrical impulses, propagated as action potentials throughout the cell and its ...
[9]
The Forces that Create Membrane Potentials - Neuroscience - NCBI
For a simple hypothetical system with only one permeant ion species, the Nernst equation allows the electrical potential across the membrane at equilibrium to ...
[10]
A quantitative description of membrane current and its application to ...
This paper by Hodgkin and Huxley provides a quantitative description of membrane current and its application to conduction and excitation in nerve.
[11]
Pyramidal Neurons in Different Cortical Layers Exhibit Distinct ...
Jun 19, 2017 · PNs in different cortical layers have distinct morphology, physiology and functional roles in neural circuits.
[12]
Histology, Purkinje Cells - StatPearls - NCBI Bookshelf - NIH
Nov 14, 2022 · As an important part of the cerebellar circuits, Purkinje cells are necessary for well-coordinated movement and other areas of function, such ...Introduction · Structure · Function · Histochemistry and...
[13]
Glial Cells - an overview | ScienceDirect Topics
Glial cells are defined as non-neuronal cells in the nervous system that provide structural support, assist in metabolism, and protect neurons, with certain ...
[14]
The Search for True Numbers of Neurons and Glial Cells in the ...
The human brain was believed to contain about 100 billion neurons and one trillion glial cells, with a glia:neuron ratio of 10:1.
[15]
Glial Cells and Their Function in the Adult Brain - Frontiers
The total glial cell population can be subdivided into four major groups: (1) microglia, (2) astrocytes, (3) oligodendrocytes, and (4) their progenitors NG2- ...Missing: ependymal | Show results with:ependymal
[16]
Glial cells: Histology and clinical notes - Kenhub
Jul 27, 2015 · There are four general types of glia in the central nervous system; astrocytes, oligodendrocytes, microglia, and ependymal cells. Some of these ...
[17]
Role of pro-inflammatory cytokines released from microglia in ...
Microglial activation results in their production of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α. While release of these factors is typically ...
[18]
Review Tripartite synapses: astrocytes process and control synaptic ...
'Tripartite synapse' refers to a concept in synaptic physiology based on the demonstration of the existence of bidirectional communication between astrocytes ...Missing: paper | Show results with:paper
[19]
Evolution of astrocytes: From invertebrates to vertebrates - Frontiers
The first glial cells are visible in Acoelomorpha, although they became more complex (e.g., sheath glia) in Caenorhabditis elegans and Anellida, with anatomical ...
[20]
Nervous Systems | Organismal Biology
While there is great diversity among different vertebrate nervous systems, they all share a basic structure: a CNS that contains a brain and spinal cord and a ...
[21]
Brain Facts and Figures
Average Brain Weights (in grams). Species, Weight (g), Species, Weight (g). adult human, 1,300 - 1,400, newborn human, 350 - 400.
[22]
Neuroanatomy, Corticospinal Cord Tract - StatPearls - NCBI Bookshelf
Aug 14, 2023 · The corticospinal tract, AKA, the pyramidal tract, is the major neuronal pathway providing voluntary motor function.
[23]
Anatomy, Head and Neck: Blood Brain Barrier - StatPearls - NCBI
[1] The BBB is composed of endothelial cells (ECs), pericytes (PCs), capillary basement membrane, and astrocyte end-feet, all of which aim to shield the brain ...Introduction · Structure and Function · Embryology · Clinical Significance
[24]
The Peripheral Nervous System - SEER Training Modules
The peripheral nervous system consists of the nerves that branch out from the brain and spinal cord. These nerves form the communication network between the CNS ...Missing: vertebrate | Show results with:vertebrate
[25]
Chapter 1: Overview of the Nervous System
The PNS is divided into two systems: the visceral system and the somatic system. The visceral system is also known as the autonomic system.Missing: vertebrate | Show results with:vertebrate
[26]
Complex Homology and the Evolution of Nervous Systems - PMC
Dec 30, 2015 · Placozoans, sponge larvae, and cnidarian larvae without nervous systems have motility and taxis no less complex than cnidarian larvae with ...
[27]
Evolution of eumetazoan nervous systems: insights from cnidarians
The nervous system of Nematostella, as of other cnidarians, is comprised of two interconnected neuronal networks, one in the ectoderm and one in the endoderm.
[28]
Dynamics of neural activity in early nervous system evolution - PMC
Aug 6, 2024 · Cnidarians and bilaterians diverged roughly 600 million years ago, shortly after the origin of nervous systems: the conservation of key ...
[29]
Early animal evolution and the origins of nervous systems - PMC
It has been traditional to regard nervous systems as having evolved once only, at the base of the so-called Epitheliozoa (i.e. Ctenophora, Cnidaria and ...<|separator|>
[30]
Convergent evolution of bilaterian nerve cords - PubMed Central - NIH
It has been hypothesized that a condensed nervous system with a medial ventral nerve cord is an ancestral character of Bilateria.Missing: mushroom | Show results with:mushroom
[31]
The mushroom bodies - prominent brain centers of Arthropods and ...
Aug 6, 2025 · The mushroom bodies are the most prominent neuropils in the brains of various arthropods, onychophorans, and some vagile polychaetous annelids ( ...
[32]
Evolution of cephalopod nervous systems - ScienceDirect.com
six times the number in the mouse brain. Of these, ...
[33]
Cephalopod Brains: An Overview of Current Knowledge to Facilitate ...
Jul 20, 2018 · In the octopus, as far other cephalopod species, the 'brain' is assembled through a series of ganglia of molluscan origin to form lobes that ...
[34]
Evolution of the Chordate Telencephalon - PMC - PubMed Central
Here we review the origin and diversification of the telencephalon with a focus on key evolutionary innovations shaping the neocortex at multiple levels of ...
[35]
The cellular basis of behavior in Aplysia - ScienceDirect.com
The long-term cyclic processes which we have discovered in some of these neurons may underlie behaviors such as sleep and waking, reproductive cycles, and ...
[36]
The evolution of mammalian brain size | Science Advances
Apr 28, 2021 · It has long been recognized that brain size scales with body size following a standard linear allometric power law (6).
[37]
Learning the dynamics of realistic models of C. elegans nervous ...
Jan 10, 2023 · The complete connectome of C. elegans contains 302 neurons for the adult hermaphrodite and 385 neurons for the male, but for the latter ...
[38]
insights into the evolution of ion channels in metazoans - PMC
How functional diversification of ion channels contributed to the evolution of nervous systems may be understood by studying organisms at key positions in the ...
[39]
Evolution of voltage-gated ion channels at the emergence of Metazoa
Feb 15, 2015 · In this review, we describe in detail the current state of knowledge regarding the evolution of these channels with a special emphasis on the metazoan lineage.Introduction: the superfamily of... · The multiple evolutionary...
[40]
Spemann-Mangold Organizer | Embryo Project Encyclopedia
Jan 12, 2012 · To explore neural plate induction, Spemann first performed a transplant experiment that was nearly identical to the later organizer experiment.
[41]
Neuroanatomy, Neural Tube Development and Stages - NCBI - NIH
The entire nervous system forms via the process called neurulation in which neural tube and neural crest form initially. In the third week of embryogenesis ...Introduction · Structure and Function · Embryology · Blood Supply and Lymphatics
[42]
Nervous System Regionalization Entails Axial Allocation before ...
Oct 18, 2018 · An early role for WNT signaling in specifying neural patterns of Cdx and Hox gene expression and motor neuron subtype identity. PLoS Biol ...
[43]
Patterning the Vertebrate Neural Plate by Wnt Signaling - NCBI - NIH
In this chapter, the contribution of Wnt signaling to the induction and patterning of the nervous system will be reviewed.
[44]
Neural Tube Defects - CDC
May 20, 2025 · Neural tube defects (NTDs) are problems that occur when the neural tube does not close properly. Types The most common NTDs are spina bifida, anencephaly, and ...
[45]
The origin and evolution of chordate nervous systems - PMC
Evodevo also showed how extra genes resulting from whole-genome duplications in vertebrates facilitated evolution of new structures like neural crest.
[46]
Radial glia and radial glia-like cells: Their role in neurogenesis and ...
Nov 16, 2022 · Radial glia is a cell type traditionally associated with the developing nervous system, particularly with the formation of cortical layers in the mammalian ...
[47]
Synaptogenesis and development of pyramidal neuron dendritic ...
Jun 10, 2013 · We found that synaptogenesis occurs synchronously across cortical areas, with a peak of synapse density during the juvenile period (3–5 y).
[48]
Changes in Behavior and Neural Dynamics across Adolescent ...
Dec 13, 2023 · Some studies have found that up to 40% of synapses are pruned during adolescence (Petanjek et al., 2011). Furthermore, synaptic density ...
[49]
Maturation of the adolescent brain - PMC - PubMed Central - NIH
Dendritic pruning eradicates unused synapses and is generally considered a beneficial process, whereas myelination increases the speed of impulse conduction ...
[50]
Beyond the Hippocampus and the SVZ: Adult Neurogenesis ...
In the hippocampus, adult neurogenesis is thought to play a role in both mood regulation (i.e., affective behaviors) and cognition (i.e., learning, memory, and ...Regulation Of Svz... · Neurogenic Niches In The... · Svz-Generated Neural...
[51]
Role of Adult Neurogenesis in Hippocampus-Dependent Memory ...
Adult neurogenesis occurs in two discrete regions of the adult mammalian brain, the subgranular zone (SGZ) of the dentate gyrus (DG) and the subventricular zone ...Adult Neurogenesis And... · Figure 6. Erk5 Icko Mice... · Enhancing Memory Formation...
[52]
Neurotrophic Factor Control of Adult SVZ Neurogenesis - PMC
One growth factor implicated in the control of adult SVZ neurogenesis is brain-derived neurotrophic factor (BDNF). BDNF exists in two forms (proBDNF and mature ...
[53]
Review A Brief History of Long-Term Potentiation - ScienceDirect.com
Jan 18, 2017 · Since the discovery of long-term potentiation (LTP) in 1973, thousands of papers have been published on this intriguing phenomenon.
[54]
The interplay between Hebbian and homeostatic synaptic plasticity
Oct 28, 2013 · Durable forms of synaptic plasticity known as Hebbian plasticity, including long-term potentiation (LTP) and long-term depression (LTD), have ...
[55]
The foundations of development and deprivation in the visual system
The pioneering work of Torsten Wiesel and David Hubel on the development and deprivation of the visual system will be summarised
[56]
Effect of Environmental Enrichment on the Brain and on Learning ...
Mar 31, 2021 · [7] found that rats exposed to environmental enrichment had increased cortical thickness, especially in the occipital cortex. Environmental ...
[57]
The neuroplastic brain: current breakthroughs and emerging frontiers
Jul 1, 2025 · In summary, neuroplastic processes gradually slow with age but do not cease. Structured exercise regimens can elevate BDNF and preserve ...
[58]
Lifestyle Modulators of Neuroplasticity: How Physical Activity, Mental ...
For example, physical activity and diet modulate common neuroplasticity substrates (neurotrophic signaling, neurogenesis, inflammation, stress response, and ...
[59]
Structural and functional plasticity of dendritic spines - NIH
It is clear that the structural plasticity of dendritic spines is related to changes in synaptic efficacy, learning and memory, and other cognitive processes.
[60]
Extensive Turnover of Dendritic Spines and Vascular Remodeling in ...
Apr 11, 2007 · We used in vivo two-photon imaging to examine changes in dendritic and vascular structure in cortical regions recovering from stroke.
[61]
Physiology, Action Potential - StatPearls - NCBI Bookshelf - NIH
An action potential is a rapid voltage change across a membrane, involving depolarization (sodium) and repolarization (potassium) in neurons.
[62]
Synaptic Transmission - Basic Neurochemistry - NCBI Bookshelf - NIH
The short delays between Ca2+ influx and exocytosis have important implications for the mechanism of fusion of synaptic vesicles (Chap. 9). In this short time, ...
[63]
Chemical Synapses - Neuroscience - NCBI Bookshelf - NIH
The Ca2+-dependent fusion of synaptic vesicles with the terminal membrane causes their contents, most importantly neurotransmitters, to be released into the ...Missing: Ca2+ | Show results with:Ca2+
[64]
Postsynaptic Potentials – Foundations of Neuroscience
Excitatory postsynaptic potentials (EPSPs) result from sodium influx, depolarizing the membrane and increasing the likelihood of action potential firing.Postsynaptic Potentials · Inhibitory Postsynaptic... · Summation Of Inputs
[65]
[PDF] Principles of Dendritic Integration - Janelia Research Campus
A particularly critical factor affecting PSP summation is the membrane time constant (τm), which is given by the product of Rm and Cm. For any change in ...
[66]
Overview of CNS Neurotransmitters - TMedWeb
Dec 6, 2021 · Glutamate is the major excitatory neurotransmitter in the CNS. Glutamate interacts with at least 4 receptor subtypes.
[67]
[PDF] Chapter 6 - Neurotransmitters and Their Receptors - Princeton Math
Neuropeptides are rel- atively large transmitter molecules composed of 3 to 36 amino acids. Individual amino acids, such as glutamate and GABA, as well as the ...
[68]
Synaptic Transmission
There are two kinds of receptors: ionotropic (direct) and metabotropic (indirect). Inactivation: The neurotransmitter is degraded either by being broken ...<|control11|><|separator|>
[69]
Neurotransmitter Release and Removal - Neuroscience - NCBI - NIH
The mechanisms by which neurotransmitters are removed vary but always involve diffusion in combination with reuptake into nerve terminals or surrounding glial ...
[70]
Architectures of neuronal circuits - Science
Sep 3, 2021 · For example, feedforward excitation allows information to propagate across neural regions, with convergent and divergent excitation to integrate ...
[71]
Architectures of Neuronal Circuits - PMC - PubMed Central
Two widely used motifs are feedforward and feedback inhibition (Fig. 2B). In feedforward inhibition, an inhibitory neuron receives input from a presynaptic ...
[72]
Long-Range Neuronal Circuits Underlying the Interaction between ...
Furthermore, within a layer, a neuron's projection pattern can determine the strength of specific types of input.
[73]
Spinal Reflex: Anatomy and Examples - Kenhub
Based on how many neurons participate in one arc, the reflexes can be monosynaptic or polysynaptic. To understand the structure of the spinal cord and spinal ...Missing: withdrawal | Show results with:withdrawal
[74]
Spinal Reflexes – Introduction to Neurobiology
Unlike the stretch reflex, the withdrawal reflex is a polysynaptic reflex, meaning interneurons are present between the sensory neurons and the motor neurons.Missing: arc | Show results with:arc
[75]
Specific neural substrate linking respiration to locomotion - PNAS
To further confirm that the MLR connects to the respiratory central pattern generator (CPG), we performed trains of electrical stimulation in the MLR. We found ...
[76]
Basal Ganglia (Section 3, Chapter 4) Neuroscience Online
The basal ganglia and motor cortex form a processing loop whereby the basal ganglia enables the proper motor program stored in motor cortex circuits via the ...
[77]
The Theta Rhythm of the Hippocampus: From Neuronal and Circuit ...
This review focuses on the neuronal and circuit mechanisms involved in the generation of the theta (θ) rhythm and of its participation in behavior.Abstract · Introduction · Hippocampal Theta Rhythm... · Interaction of Theta with...
[78]
Convergence, Divergence, and Reconvergence in a Feedforward ...
Dec 2, 2015 · We find that both convergence and reconvergence improve the ability of a decoder to detect a stimulus based on a single neuron's spike train.
[79]
Keeping Your Brain in Balance: Homeostatic Regulation of Network ...
Aug 8, 2024 · Synaptic and intrinsic homeostasis cooperate to optimize single neuron response properties and tune integrator circuits. . J. Neurophysiol ...
[80]
The giant escape neurons of crayfish: Past discoveries and present ...
Dec 20, 2022 · Crayfish are equipped with two prominent neural circuits that control rapid, stereotyped escape behaviors. Central to these circuits are ...
[81]
Physiology, Sensory System - StatPearls - NCBI Bookshelf
May 6, 2023 · General senses include touch, pain, temperature, proprioception, vibration, and pressure. Special senses include vision, hearing, taste, and smell.
[82]
Somatosensory Systems (Section 2, Chapter 2) Neuroscience Online
The somatosensory systems process information about, and represent, several modalities of somatic sensation (i.e., pain, temperature, touch, proprioception).
[83]
Primary Sensory Areas - an overview | ScienceDirect Topics
Primary sensory areas are specific regions of the cerebral cortex that receive direct projections from sensory relay nuclei of the thalamus.
[84]
Neuroanatomy, Posterior Column (Dorsal Column) - StatPearls - NCBI
Apr 8, 2023 · The dorsal column, also known as the dorsal column medial lemniscus (DCML) pathway, deals with the conscious appreciation of fine touch, two-point ...
[85]
The Dorsal Column-Medial Lemniscus System - Neuroscience - NCBI
The dorsal column-medial lemniscus pathway carries the majority of information from the mechanoreceptors that mediate tactile discrimination and proprioception.
[86]
Motor Cortex (Section 3, Chapter 3) Neuroscience Online
Individual alpha motor neurons control the force exerted by a particular muscle, and spinal circuits can control sophisticated and complex behaviors such as ...Missing: extrapyramidal | Show results with:extrapyramidal
[87]
Neuroanatomy, Extrapyramidal System - StatPearls - NCBI Bookshelf
The EPS is essential in maintaining posture and regulating involuntary motor functions. In particular, the EPS provides: Postural tone adjustment. Preparation ...
[88]
Neuroanatomy, Pyramidal Tract - StatPearls - NCBI Bookshelf - NIH
The pyramidal tract, especially the corticospinal tract, plays a significant role in controlling voluntary muscular movements. As a result, severe lesions can ...
[89]
Extrapyramidal and Pyramidal Tracts - Physiopedia
The Extrapyramidal and Pyramidal tracts are the pathways by which motor signals are sent from the brain to lower motor neurones.Missing: hierarchical planning efferent
[90]
The Descending Tracts - Pyramidal - TeachMeAnatomy
The extrapyramidal tracts originate in the brainstem, carrying motor fibres to the spinal cord. They are responsible for the involuntary and automatic control ...Missing: hierarchical planning efferent
[91]
Cerebellum, Predictions and Errors - PMC - PubMed Central
Jan 15, 2019 · The cerebellum has been viewed as a key component of the motor system providing predictions about upcoming movements and receiving feedback about motor errors.
[92]
[PDF] Imitation, Empathy, and Mirror Neurons - Marco Iacoboni Lab
Sep 15, 2008 · A re- cent discovery in the monkey premotor cortex has sparked a whole series of new studies, in monkeys and humans, that are relevant to ...
[93]
Mechanoreceptors Specialized for Proprioception - NCBI - NIH
The major function of muscle spindles is to provide information about muscle length (that is, the degree to which they are being stretched). A detailed account ...<|separator|>
[94]
Neuroanatomy, Vestibulo-ocular Reflex - StatPearls - NCBI Bookshelf
Jul 25, 2023 · The vestibulo-ocular reflex (VOR) maintains stable perception during movement by moving eyes opposite to head movement, involving sensory, ...
[95]
Reflections on agranular architecture: predictive coding in the motor ...
The agranular architecture of motor cortex lacks a functional interpretation. Here, we consider a 'predictive coding' account of this unique feature.
[96]
Dementia - World Health Organization (WHO)
Mar 31, 2025 · In 2021, 57 million people had dementia worldwide, over 60% of whom live in low-and middle-income countries. Every year, there are nearly 10 ...
[97]
Unraveling Molecular and Genetic Insights into Neurodegenerative ...
One defining characteristic of Alzheimer's disease (AD) pathology is the formation of neurofibrillary tangles (NFTs). NFTs consist of hyperphosphorylated tau ...
[98]
Apoe4 and Alzheimer's Disease Pathogenesis—Mitochondrial ...
Jan 1, 2023 · APOE ε4 allele (ApoE4) is the primary genetic risk factor for sporadic Alzheimer's disease (AD), expressed in 40–65% of all AD patients.
[99]
Alzheimer's Disease Facts and Figures
Prevalence · An estimated 7.2 million Americans age 65 and older are living with Alzheimer's in 2025. · About 1 in 9 people age 65 and older (11%) has Alzheimer's ...
[100]
Pathology of Neurodegenerative Diseases - PMC - PubMed Central
In this review, we detail the human pathology of select neurodegenerative disorders, focusing on their main protein aggregates.
[101]
Amyotrophic lateral sclerosis and neurodegenerative diseases
Jun 20, 2025 · These findings indicate that ALS may share common pathological features with other neurodegenerative diseases, including Alzheimer's disease (AD) ...
[102]
Uncovering mechanisms of brain inflammation in Alzheimer's ...
In this review, we focus on brain lipids and their connection to inflammation in persons at genetic risk for AD based on apolipoprotein E ε4 allele (APOE4) ...
[103]
Traumatic Brain Injury (TBI)
Jul 21, 2025 · DAI commonly happens in auto accidents, falls, or sports injuries. DAI can disrupt and break down communication among nerve cells in the brain.What is a traumatic brain injury... · How is a traumatic brain injury...
[104]
Stroke risk following traumatic brain injury: Systematic review and ...
Traumatic brain injury appears to be associated with increased stroke risk regardless of severity or subtype of traumatic brain injury. There was some evidence ...Missing: nervous | Show results with:nervous
[105]
Is Multiple Sclerosis an Autoimmune Disease? - PubMed Central - NIH
There is strong evidence that MS is, at least in part, an immune-mediated disease. There is less evidence that MS is a classical autoimmune disease.
[106]
Neurodegenerative Diseases: Multifactorial Conformational ...
Neurodegenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis diseases are the consequence of misfolding and ...