Neuro-March1

Development of the Nervous System

The study of how the human nervous system forms and matures across embryonic, fetal, and postnatal periods, involving genetically programmed processes and activity-dependent refinement of neural circuits.

CNS development overview

Development of the human nervous system occurs during embryonic, fetal, and postnatal periods, with prenatal stages forming gross structures and early synapses largely under genetic control, and postnatal stages characterized by glial proliferation, synaptogenesis, myelination, dendritic branching, and activity-dependent circuit refinement.

Prenatal development

The developmental period before birth during which gross structures of the nervous system are formed, some synapses are established, and development is mostly governed by hardwired genetic programs.

Postnatal development

The developmental period after birth characterized by addition of glial cells, formation of many more synapses, myelination of axons, increased dendritic branching, and activity-dependent processes that refine neural circuits.

Embryonic period

0-8 weeks after fertilization

Fetal period

8 weeks to birth

Zygote

The single fertilized cell formed at conception that undergoes repeated cell divisions to begin embryonic development.

Blastocyst

A fluid-filled structure formed from early cell divisions of the zygote, containing an inner cell mass and lined by trophoblasts.

Inner cell mass (ICM)

A cluster of cells within the blastocyst that gives rise to the embryo.

Trophoblasts

Cells lining the blastocyst that contribute to formation of the placenta.

Bilaminar embryonic disc

A two-layered structure formed after blastocyst reorganization, consisting of epiblast and hypoblast layers.

Epiblast

A flat disc of cells in the bilaminar embryonic disc that gives rise to the embryo.

Hypoblast

A layer of cells in the bilaminar embryonic disc that forms the yolk sac.

Trophoblast

forms trophectoderm, which gives rise to placenta

Gastrulation

A developmental process occurring between days 13–19 in which epiblast cells migrate through the primitive streak to form three germ layers

Primitive pit

A midline depression formed by epiblast cells that elongates to become the primitive streak during gastrulation.

Primitive streak

An elongated structure formed from the primitive pit that serves as the site where epiblast cells ingress to form germ layers.

Ingression waves

Sequential migrations of epiblast cells through the primitive streak that generate the endoderm and mesoderm layers.

Endoderm

The innermost germ layer formed during gastrulation that gives rise to the lining of digestive and respiratory organs and several glands.

Mesoderm

The middle germ layer formed during gastrulation that develops into muscles, bones, connective tissue, the cardiovascular system, and blood cells.

Ectoderm

The outer germ layer formed from epiblast cells that do not ingress during gastrulation, which gives rise to the nervous system, skin, and related structures.

Neural induction

The process beginning around 17 days after fertilization that specifies neural versus nonneural ectoderm, initiating nervous system formation.

Notochord

A midline structure of mesodermal cells that releases morphogens and inhibits BMP signaling to induce neural plate formation.

Neural plate

A thickened region of ectoderm formed in response to neural induction, wider rostrally than caudally, that gives rise to the central nervous system.

Neurulation

The process during weeks 3–4 in which the neural plate folds and closes to form the neural tube.

Primary neurulation

The initial folding of the neural plate into a neural groove and subsequent closure into a neural tube, beginning around day 20 and closing rostrally by day 24 and caudally by day 26.

Secondary neurulation

A process following primary neurulation in which neural ectoderm and some endoderm cells form a medullary cord that cavitates and merges with the caudal neural tube.

Neural tube

The closed structure formed by neurulation that gives rise to the brain and spinal cord.

Neural tube defects

Developmental abnormalities such as spina bifida that result from failure of the neural tube to close properly.

Regionalization & patterning in the CNS

The process by which the rostral neural tube forms three primary vesicles, then five vesicles, which differentiate into specific brain structures under inductive signaling influences.

Neurogenesis

The formation of new neurons from progenitor cells during development.

Radial glial cells

Cells that generate neural progenitors and provide scaffolding to guide migrating neurons during development.

Diencephalon

The vesicle of the neural tube that gives rise to the thalamus and hypothalamus.

Neural crest cells

Cells originating at the edges of the neural tube that migrate to form structures of the peripheral nervous system.

Electrical Properties of Neurons

The principles governing ion movement and membrane potentials that enable neurons to generate and propagate electrical signals.

Selective permeability

The property of the neuronal membrane that allows certain molecules, such as gases and small hydrophobic molecules, to pass freely while restricting ions and large polar molecules.

Transmembrane proteins

Membrane-spanning proteins that include integral membrane proteins with hydrophobic transmembrane domains and hydrophilic extracellular and cytoplasmic regions, and peripheral proteins that associate with membrane complexes without spanning the bilayer.

Ion channels

Membrane-spanning proteins with an outer barrel structure and inner aqueous pore that allow facilitated diffusion of specific ions based on selectivity and gating mechanisms.

Leak ion channels

Non-gated ion channels that are always open and allow ions to move according to electrochemical driving force, largely determining resting membrane potential via K+ leakage.

Voltage-gated channels

Ion channels that open in response to changes in membrane potential, essential for action potentials and calcium-dependent processes such as neurotransmitter release.

Ligand-gated ion channels

Ion channels that open upon binding of a chemical ligand, typically selective for cations or chloride, and may have multiple receptor sites.

Electrical gradient

The force on charged molecules due to differences in electrical charge across the membrane.

Chemical gradient

The force driving ions from regions of high concentration to regions of low concentration.

Electrochemical gradient

The combined influence of electrical and chemical gradients on ion movement, calculated as membrane potential minus equilibrium potential.

Equilibrium potential

The membrane potential at which the electrical and chemical gradients for a specific ion are balanced, resulting in no net movement of that ion.

Nernst equation

The mathematical equation used to calculate the equilibrium potential of an ion based on its valence, temperature, and intra- and extracellular concentrations.

Active transporters

Membrane proteins that move ions against their concentration gradients using energy, maintaining ion concentration differences across the membrane.

Signaling Between Neurons

The processes by which neurons communicate via electrical or chemical synapses.

Neurotransmission

Communication between neural cells or between neurons and target cells through release and reception of signaling molecules.

Volume transmission

Diffusion of signaling molecules into cerebrospinal fluid or extracellular fluid to activate receptors at distant sites.

Synaptic transmission

Communication occurring at a synapse between a presynaptic neuron and a postsynaptic target cell.

Electrical synapse

A synapse in which gap junction channels formed by connexons allow direct flow of ions and second messengers between neurons.

Chemical synapse

A synapse in which neurotransmitters are released from a presynaptic neuron, diffuse across the synaptic cleft, and bind to receptors on a postsynaptic cell.

Synaptic cleft

The space between presynaptic and postsynaptic cells at a chemical synapse.

Connexons

Transmembrane protein complexes composed of connexins that form channels in gap junctions of electrical synapses.

Small (clear) vesicles

Vesicles located in axon terminals that store most conventional small-molecule neurotransmitters.

Large dense-core vesicles

Vesicles containing neuropeptides found in the cell body, axon, and axon terminal.

Neurotransmitter Release

Calcium Channels

Neurotransmitters

Chemical messengers present in presynaptic neurons that are released upon stimulation and produce responses in target cells.

Conventional small-molecule neurotransmitters

Neurotransmitters including amines, purines, monoamines, and amino acids that meet classical criteria for neurotransmission.

Neuropeptides

Peptide neurotransmitters that often function as neuromodulators.

Unconventional neurotransmitters

Signaling molecules that do not meet all classical criteria for neurotransmitters.

Acetylcholine

Location & Function

ChAT (enzyme)

Choline acetyltransferase, the enzyme that synthesizes acetylcholine from choline and acetyl-coenzyme A.

Vesicular ACh transporter (VAChT)

A transporter that loads acetylcholine into synaptic vesicles using a proton gradient.

Nicotinic ACh receptors (nAChR)

Ionotropic, nonselective cation channels permeable to Na+, K+, and sometimes Ca2+, that depolarize the membrane when activated and are typically excitatory.

Muscarinic ACh receptors (mAChR)

Metabotropic G-protein coupled receptors with five subtypes that mediate slower modulatory effects of acetylcholine.

Glutamate

Location & Function

AMPA receptors (AMPARs)

Ionotropic glutamate receptors that are nonselective cation channels mediating fast excitatory responses.

Kainate receptors (KaRs)

Ionotropic glutamate receptors that are nonselective cation channels contributing to excitatory transmission.

NMDA receptors (NMDARs)

Ionotropic glutamate receptors that are nonselective cation channels requiring glycine as a co-agonist and membrane depolarization to open, mediating excitatory responses.

Metabotropic glutamate receptors (mGluRs)

G-protein coupled glutamate receptors with multiple subtypes that mediate neuromodulatory effects.

GABA-A receptors

Ionotropic chloride channels that mediate inhibitory neurotransmission.

GABA-B receptors

Metabotropic receptors that mediate inhibitory effects through G-protein signaling pathways.

Glycine Ionotropic glycine receptor

An ionotropic chloride channel that mediates inhibitory neurotransmission.

5HT3R

The only ionotropic monoamine receptor, a nonselective cation channel mediating excitatory responses to serotonin.

D1-like receptors

Metabotropic dopamine receptors involved in modulatory signaling.

D2-like receptors

Metabotropic dopamine receptors that modulate neuronal excitability and signaling.

Alpha

Metabotropic adrenergic receptors responsive to norepinephrine and epinephrine.

Beta

Metabotropic adrenergic receptors responsive to norepinephrine and epinephrine.

Neuropharmacology & Substance use

The study of how exogenous drugs affect neurotransmission, receptor function, clearance mechanisms, and reward circuitry.

EXOGENOUS DRUG EFFECTS CAN BE EXCITATORY, INHIBITORY, OR MODULATORY

Drugs can enhance, suppress, or modulate neural activity depending on their mechanisms of action.

Agonist

A molecule that mimics a neurotransmitter and activates its receptor.

Antagonist

A molecule that blocks a receptor and prevents ligand binding.

Allosteric modulator

A molecule that binds to a receptor at a site other than the primary ligand site and alters receptor function.

Block reuptake

A drug effect that inhibits transporter-mediated reuptake of neurotransmitters, increasing their synaptic concentration.

Block degradation enzymes

A drug effect that inhibits enzymes responsible for neurotransmitter breakdown, prolonging their action.

Pharmacodynamics

The study of how drugs produce effects in the body, characterized by stochastic processes and described by dose-response curves.

Dopamine

A neurotransmitter central to reward circuitry, functioning as a learning signal associated with prediction error rather than simple pleasure.

Prediction error

A dopamine-mediated signal representing the difference between expected and actual reward outcomes.

Substance use Disorder (DSM-5)

A diagnosis requiring at least two criteria within a 12-month period, including impaired control, social impairment, risky use, tolerance, and withdrawal.

Tolerance

A state in which repeated use of a substance results in reduced effect, requiring higher doses to achieve the same outcome.

Withdrawal

The occurrence of characteristic symptoms upon cessation of a substance, or use of the substance to avoid such symptoms.

Incentive sensitization model

A theory of addiction proposing a shift from liking a drug to wanting it, driven by sensitization of motivational circuitry.

GABA

Location & Function

GABA

Synthesis & Storage

GABA

Receptors & Reuptake

Glycine

Location & Function

Glycine

Receptors

Serotonin (5-HT)

Location & Function