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Chapter 4. Cellular and Molecular Biology of the Neuron

A. Kimberley McAllister, Ph.D.; W. Martin Usrey, Ph.D.; Stephen C. Noctor, Ph.D.; Stephen Rayport, M.D., Ph.D.
DOI: 10.1176/appi.books.9781585623402.291674

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Neuropsychiatric disorders are due to disordered functioning of neurons and, in particular, their synapses (Charney et al. 2004; Graham et al. 2002; Waxman 2005). Many neuropsychiatric disorders arise from aberrations in neurodevelopmental mechanisms. In the initial stages of brain development, cell–cell interactions are the dominant force in the assembly of the brain (Wichterle et al. 2002). As circuits form, individual neurons and connections are pruned on an activity-dependent basis, driven by intrinsic activity and competition for trophic factors. Neurogenesis does not stop with maturation but in fact continues in some brain regions and appears to be required for mood regulation (Santarelli et al. 2003; Warner-Schmidt and Duman 2006). With further maturation, experience becomes the dominant force in shaping neuronal connections and regulating their efficacy. In the mature brain, these neurodevelopmental mechanisms are harnessed in muted form and mediate most plastic processes (Black 1995; Kandel and O'Dell 1992). Neuropsychiatric disorders arising from problems in early brain development are more likely to be intrinsically or genetically based, whereas those arising during later stages are more likely to be experience-based (Toga and Thompson 2005). In senescence, neurodegenerative processes may unravel neural circuits by aberrantly engaging neurodevelopmental mechanisms (Luo and O'Leary 2005).

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FIGURE 4–1. Functional organization of the neuron.Neurons have distinct cellular regions subserving the input, integration, conduction, and output of information: the dendrites, cell body, axon, and synaptic specializations, respectively. Excitatory and inhibitory neurotransmitters released by other neurons induce depolarizing or hyperpolarizing current flow in dendrites. These currents converge in the cell body, and if the resulting polarization is sufficient to bring the initial segment of the axon to threshold, an action potential is initiated. The action potential travels down the axon, speeded by myelination, to reach the synaptic terminals. Axon terminals form synapses with other neurons or effector cells, renewing the cycle of information flow in postsynaptic cells. As in all cells, the cell body (or perikaryon) is also the repository of the neuron's genetic information (in the nucleus) and the principal site of macromolecular synthesis.Source. Reprinted from Kandel ER: "Nerve Cells and Behavior," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 19–35.Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–2. Opening of ion channels gives rise to the action potential.The upper traces show the two principal currents shaping the action potential, sodium (Na+) and potassium (K+) currents. Once a neuron reaches threshold for firing an action potential, voltage-activated Na+ channels open, giving rise to a rapid inward Na+ current and to the rapid rising phase of the action potential (green trace; membrane potential, EM). Once the membrane is depolarized, Na+ channels rapidly inactivate, reducing the Na+ current (purple trace) and thereby contributing to the falling phase of the action potential. Then, outward K+ current (yellow trace) activates, driving the falling phase of the action potential. K+ channels are slow to open but stay open for much longer than Na+ channels, pulling the EM back to the resting level. ENa and EK represent the reversal potentials for Na+ and K+, respectively, to which the opening of channels drives the membrane potential (EM). The lower schematic shows the local circuit currents that underlie the propagation of the action potential. The intense loop on the left spreads the depolarization to the right into unexcited membrane, which then renews the cycle, depolarizing the next segment and thereby propagating the action potential.Source. Reprinted from Hille B, Catterall WA: "Electrical Excitability and Ion Channels," in Basic Neurochemistry: Molecular, Cellular and Medical Aspects, 7th Edition. Edited by Siegel GJ, Albers RW, Brady S, Price DL. Burlington, MA, Elsevier Academic, 2006, pp. 95–109. Copyright 2006. Used with permission from Elsevier.

FIGURE 4–3. Action potential conduction in myelinated axon.Panel A. Schematic of a myelinated axon. Oligodendrocytes produce the insulating myelin sheath that surrounds the axon in segments. Myelination restricts current flow to the gaps between myelin segments, the nodes of Ranvier, where sodium (Na+) channels are concentrated. The result is a dramatic enhancement of the conduction velocity of the action potential. Panel B. Because Na+ channels are activated by membrane depolarization and also cause depolarization, they have regenerative properties. This underlies the "all-or-nothing" properties of the action potential and also explains its rapid spread down the axon. The action potential is an electrical wave; as each node of Ranvier is depolarized, it in turn depolarizes the subsequent node. Panel C. The Na+ current underlying the action potential is shown in three successive images at 0.5-millisecond intervals and corresponds to the current traces in Panel B. As the action potential (red shading) travels to the right, Na+ channels go from closed to open to inactivated to closed. In this way, an action potential initiated at the initial segment of the axon conducts reliably to the axon terminals. Because Na+ channels temporarily inactivate after depolarization, there is a brief refractory period following the action potential that blocks backward spread of the action potential and thus ensures reliable forward conduction.Source. Reprinted from Purves D, Augustine GJ, Fitzpatrick D, et al. (eds): Neuroscience, 3rd Edition. Sunderland, MA, Sinauer Associates, 2004, p. 64. Used with permission.

FIGURE 4–4. Intrinsic properties determine neuronal responses.Many CNS neurons respond differently to the same inputs, depending on their level of depolarization. Panel A. Thalamic neurons spontaneously generate bursts of action potentials, resulting from interactions between an inward pacemaker current and a calcium (Ca2+) current. Depolarization of these neurons changes their firing to a tonic mode. Panel B. Action potential bursts at higher time resolution from trace in Panel A. Panel C. Higher time resolution of currents in the tonic mode from Panel A. Ih and IT = the currents through a hyperpolarization-activated channel and a T-type calcium channel, respectively.Source. Reprinted from McCormick DA: "Membrane Potential and Action Potential," in Fundamental Neuroscience, 2nd Edition. Edited by Squire LR, Roberts JL, Spitzer NC, et al. San Diego, CA, Academic Press, 2003, pp. 139–161. Copyright Elsevier 2004. Used with permission.

FIGURE 4–5. Modes of interneuronal communication.Panel A. Different connection patterns dictate how information flows between neurons. In synaptic divergence, one neuron (a) may disseminate information to several postsynaptic cells (b–f) simultaneously (information flow is shown by arrows). Alternatively, in the case of synaptic convergence, a single neuron (d) may receive input from an array of presynaptic neurons (a–c). In presynaptic inhibition, one neuron (b) can modulate information flowing between two other neurons (from a to c) by influencing neurotransmitter release from the presynaptic neuron's terminals; this can be inhibitory (as shown) or facilitatory. Panel B. Neurons may modulate their own actions. In feedforward inhibition, the presynaptic cell (a) may directly activate a postsynaptic cell (b) and at the same time modulate its effects via activation of an inhibitory cell (c), which in turn inhibits the cell (b). In recurrent inhibition, a presynaptic cell (a) activates an inhibitory cell (b) that synapses back onto the presynaptic cell (a), limiting the duration of its activity. ap = action potential; li = lateral inhibition; ri = recurrent inhibition.Source. Adapted from Shepherd GM, Koch C: "Introduction to Synaptic Circuits," in The Synaptic Organization of the Brain, 3rd Edition. Edited by Shepherd GM. New York, Oxford University Press, 1990, pp. 3–31.

FIGURE 4–6. Synaptic ultrastructure.Neuromuscular junctions from frog sartorius muscle were flash-frozen milliseconds after high potassium treatment to increase synaptic transmission. Panel A. Synaptic vesicles are clustered at two active zones (arrows), which are sites where vesicles fuse with the plasma membrane to release their neurotransmitter. Panel B. At higher magnification and after stimulation, omega profiles of vesicles in the process of releasing their neurotransmitter are visible.Source. Reprinted from Schwarz TL: "Release of Neurotransmitters," in Fundamental Neuroscience, 2nd Edition. Edited by Squire LR, Roberts JL, Spitzer NC, et al. San Diego, CA, Academic Press, 2003, pp. 197–224; original source Heuser JE: "Synaptic Vesicle Endocytosis Revealed in Quick-Frozen Frog Neuromuscular Junctions Treated With 4-Aminopyridine and Given a Single Electrical Shock." Society for Neuroscience Symposia 2:215–239, 1977. Copyright 1977. Used with permission.

FIGURE 4–7. Steps in synaptic transmission at a chemical synapse.Essential steps in the process of synaptic transmission are numbered. Ca2+ = calcium.Source. Reprinted from Purves D, Augustine GJ, Fitzpatrick D, et al. (eds): Neuroscience, 3rd Edition. Sunderland, MA, Sinauer Associates, 2004, p. 97. Used with permission.

FIGURE 4–8. Molecular events in synaptic vesicle docking and fusion.A coordinated set of proteins is involved in the positioning of vesicles at the presynaptic membrane and in controlling release by membrane fusion. Panel A. Many of the recently cloned synaptic vesicle proteins are integral to this process. Some of these proteins interact with the cytoskeleton to position the vesicles at the terminal, while other proteins are integral to the fusion process. In addition, several of these synaptic vesicle proteins are targets for neurotoxins that function by influencing neurotransmitter release. Panel B. The current theory for how synaptic vesicles fuse with the membrane and release neurotransmitter is called the SNARE hypothesis. Both the synaptic vesicles and the plasma membrane express specific proteins that mediate docking and fusion: v-SNAREs (synaptic vesicles) and t-SNAREs (plasma membrane). Vesicles are brought close to the membrane through interactions between VAMP (synaptobrevin), syntaxin, and SNAP-25. N-ethylmaleimide-sensitive fusion protein (NSF) then binds to the complex to facilitate fusion. Calcium (Ca2+) influx is required to stimulate fusion, but the precise binding partner for calcium and the exact events leading to fusion remain obscure. Panel C. The crystal structure of the fusion complex, as shown here, is consistent with the SNARE hypothesis. BoNT = botulinum toxin; TeNT = tetanus toxin.Source. Adapted from Kandel ER, Siegelbaum SA: "Transmitter Release," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 253–279. Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–9. Neurotransmitter transporters.Synaptic transmission in the CNS is terminated for the most part by reuptake of neurotransmitter by specific transporters with shared molecular motifs. These transporters carry neurotransmitters across membranes against concentration gradients, and thus require metabolic energy. Most often, this energy is provided by cotransport of an ion down its concentration gradient. Panel A. One family of transporters in synaptic vesicles serves to load neurotransmitter or transmitter precursors into synaptic vesicles. Panel B. A second family of transporters in the plasma membrane with eight transmembrane domains handles amino acid neurotransmitters, such as glutamate and -aminobutyric acid. Panel C. A third family of transporters in the plasma membrane with 12 transmembrane domains handles the monoamines dopamine, norepinephrine, and serotonin.Source. Reprinted from Schwartz JH: "Neurotransmitters," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 280–297. Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–10. Major intracellular signaling pathways in neurons.Ligand binding to receptors activates three major signaling pathways via G proteins. Panel A. In the cyclic adenosine monophosphate (cAMP) system, a G protein link couples ligand binding to activation of adenylyl cyclase. This in turn generates cAMP, which binds to the regulatory units (R) of cAMP-dependent protein kinase, releasing the catalytic subunits (activated protein kinase A). After being phosphorylated (activated, phosphorylated CREB), CREB binds to cAMP response elements (CREB-binding element) to regulate gene expression. Panel B. In the inositol phospholipid system, G proteins activate phospholipase C, which hydrolyzes membrane phospholipids to produce two second messengers, diacylglycerol and inositol 1,4,5-triphosphate (IP3). IP3 triggers the release of calcium (Ca2+) from the endoplasmic reticulum. Ca2+, in turn, triggers the translocation of protein kinase C (PKC) to the cell membrane, where it is activated by diacylglycerol. Because it becomes membrane bound with activation, PKC may be especially important in the modulation of membrane channels. Ca2+ released from intracellular stores may act similarly to Ca2+ that enters from outside the cell (not shown), allowing temporal coincidence through activation of voltage-dependent Ca2+ channels. Panel C. In the arachidonic acid system, G proteins may couple to phospholipase A2 (PLA2), forming arachidonic acid by hydrolysis of membrane phospholipids. Arachidonic acid is either a second messenger in its own right or a precursor of the lipoxygenase pathway giving rise to a family of membrane-permeant second messengers. The cyclooxygenase pathway is principally important outside the brain in prostaglandin production. HPETE = hydroperoxyeicosatetraenoic acid; PI = phosphatidylinositol.Source. Panels A and B reprinted from Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P: Molecular Biology of the Cell. New York, Garland Science, 2002. Copyright Garland Science/Taylor & Francis LLC, 2002. Used with permission. Panel C reprinted from Siegelbaum SA, Schwartz JH, Kandel ER: "Modulation of Synaptic Transmission: Second Messengers," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 229–252. Copyright 2000 The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–11. Selected molecular components of a typical CNS glutamatergic synapse.-Amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits are tethered to GRIP through PDZ domain interactions, and the N-methyl-d-aspartate (NMDA) receptor subunits are bound to PSD-95. Both GRIP and PSD-95 also interact with the cytoskeleton, providing a protein scaffold for glutamate receptors in the postsynaptic density. This scaffold may regulate the dynamic, activity-dependent insertion or removal of glutamate receptors from CNS synapses. GIESVKI = the amino acids critical for binding GR2 to PDZ4 and PDZ5; nNOS = neuronal nitric oxide synthase.Source. Reprinted from O'Brien RJ, Lau LF, Huganir RL: "Molecular Mechanisms of Glutamate Receptor Clustering at Excitatory Synapses." Current Opinion in Neurobiology 8:364–369, 1998. Copyright 1998. Used with permission from Elsevier.

FIGURE 4–12. Molecular mechanisms of short-term and long-term memory storage.Panel A. Schematic shows a single synaptic connection between a sensory and motor neuron in the neural circuit mediating defensive gill-withdrawal reflex in the marine snail Aplysia californica. Serotonin (5-HT) triggers an increase in synaptic strength, which underlies the animal's heightened reflex withdrawal response when stressed. In short-term sensitization (lasting on the order of an hour), one electric shock to the tail activates 5-HT interneurons (blue), activating serotonin receptors (also in blue) that activate protein kinase A (PKA), which phosphorylates existing proteins, leading to a short-term enhancement of synaptic transmission. With repeated stress, persistent elevation of cyclic adenosine monophosphate (cAMP) levels engages nuclear regulatory pathways. PKA, in turn, activates another kinase (MAPK), and together they phosphorylate cAMP response element–binding protein 2 (CREB-2), releasing active CREB-1. CREB-1 then activates directly and indirectly a series of genes in temporal sequence, locking in the activation of PKA via ubiquitin hydrolase and encoding proteins necessary for synaptic growth. One example is Aplysia cell-adhesion molecule (apCAM), a molecule important in synaptic development, which plays a similar role in the further growth of synaptic connections with learning. Panel B. The signaling mechanisms involved in sensitization are summarized in broader strokes in this schematic: 1) sensory neurons activate motor neurons via exocytic release of the excitatory transmitter glutamate; 2) stress stimuli activate protein kinase, which both enhances transmitter release locally and 3) translocates to the nucleus to orchestrate long-term changes. The proteins for growth are utilized at synapses marked by 5-HT stimulation, leading to long-term strengthening of stressed synapses.Source. Reprinted from Kandel ER: "The Molecular Biology of Memory Storage: A Dialogue Between Genes and Synapses." Science 294:1030–1038, 2001, with permission from AAAS and the Nobel Foundation. Copyright Nobel Foundation 2000.

FIGURE 4–13. Long-term potentiation (LTP) in the hippocampus.Panel A. A brain slice preparation from the rodent hippocampus is shown with the postsynaptic recording electrode in a CA1 pyramidal cell and a presynaptic stimulating electrode (coil) on the Schaffer collateral pathway axon of a CA3 pyramidal cell. Panel B. Stimulating the Schaffer collateral pathway at low frequency (once a minute) causes the CA3 axon terminals to release glutamate, which evokes a stable excitatory response (measured as the rising slope of the excitatory postsynaptic potential, EPSP; the control response is normalized to 100%). A single tetanus (blue arrow, 100 stimuli in 1 second) evokes early LTP, which is weak and lasts on the order of an hour. In contrast, with four tetani (blue and black arrows), the postsynaptic response is dramatically increased. Late LTP lasts for over 24 hours, as would be required for a synaptic mechanism encoding long-term memory.Source. Adapted from Kandel ER: "Cellular Mechanisms of Learning and the Biological Basis of Individuality," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 1247–1279. Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–14. Molecular basis for long-term potentiation in the postsynaptic membrane of a CA1 pyramidal neuron.Panel A. With sufficient stimulation (or coincident postsynaptic depolarization), N-methyl-d-aspartate (NMDA)–type glutamate receptors are activated and Ca2+ fluxes into the cell. Ca2+ activates calcium/calmodulin-dependent protein kinase II (CaMKII), which increases the responsiveness of -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)–type glutamate receptors. CaMKII can phosphorylate itself, locking it in the active mode. With continued activity, CaMKII organizes the further insertion of AMPA receptors into the postsynaptic membrane. Panel B. AMPA receptor recruitment to the postsynaptic membrane is mediated by the contractile protein actin. Actin is a ubiquitous contractile protein, the same protein involved peripherally in muscle contraction. CaMKII thus plays a pivotal role at all steps in the enhancement of synaptic transmission with long-term potentiation.Source. Reprinted from Lisman J, Schulman H, Cline H: "The Molecular Basis of CaMKII Function in Synaptic and Behavioural Memory." Nature Reviews Neuroscience 3:175–190, 2002. Copyright 2002. Used with permission from Macmillan Publishers Ltd.

FIGURE 4–15. Key events in the generation of cortical neurons during embryogenesis.Radial glial cells (R, shown in green) undergo interkinetic nuclear migration and divide asymmetrically at the ventricular surface (*) to self-renew and to generate neurons either directly (red cell) or indirectly through the generation of an intermediate progenitor cell (blue). Intermediate progenitor cells subsequently undergo terminal symmetrical division in the subventricular zone (SVZ, ) to generate two neurons. CP = cortical plate; IZ = intermediate zone; SVZ = subventricular zone; VZ = ventricular zone.Source. Reprinted from McAllister AK, Usrey WM, Noctor SC, Rayport S: "Cellular and Molecular Biology of the Neuron," in The American Psychiatric Publishing Textbook of Neuropsychiatry and Clinical Neurosciences, 5th Edition. Washington, DC, American Psychiatric Publishing, 2008, pp. 3–43.

FIGURE 4–16. Migration phases of neocortical neurons during development.During development, neocortical neurons exhibit four distinct phases in migration. Panel A. A time-lapse sequence of a retrovirally labeled neuron expressing the reporter protein green fluorescent protein (GFP) undergoing migration from the proliferative zone to the cortical plate in a cultured brain slice. The sequence begins when the neuron is in the second phase, which consists of migratory arrest for 24 hours or more (shown here at the end of phase two, t = 0 hours), followed by a third phase of retrograde migration toward the ventricle (t = 14–18 hours) and a final phase of polarity reversal and migration toward the cortical plate (CP) (t = 24–96 hours). Before initiating the final phase of radial migration, the neuron develops a leading process oriented toward the CP (white arrowhead). After 96 hours in culture, the migrating neuron had reached its destination at the top of the cortical plate. These neurons often leave a trailing axon in the ventricular zone (VZ, red arrowheads). Panel B. Schematic depicting a neuron (shown in dark green) undergoing the four phases of migration: 1) After being generated by its mother radial glial cell (R, shown in light green), the neuron commences initial radial migration, 2) migratory arrest in the SVZ, 3) retrograde migration, and 4) secondary radial migration. IZ = intermediate zone; SVZ = subventricular zone.Source. Reprinted from McAllister AK, Usrey WM, Noctor SC, Rayport S: "Cellular and Molecular Biology of the Neuron," in The American Psychiatric Publishing Textbook of Neuropsychiatry and Clinical Neurosciences, 5th Edition. Washington, DC, American Psychiatric Publishing, 2008, pp. 3–43.

FIGURE 4–17. Synapse formation of the neuromuscular junction (NMJ).Panel A. Schematic view of the molecular components of a typical NMJ. At a mature NMJ, the presynaptic terminal is separated from the postsynaptic muscle cell by the synaptic cleft. Synaptic vesicles filled with acetylcholine (ACh) are clustered at active zones, where they can fuse with the plasma membrane upon depolarization to release their transmitter into the synaptic cleft. Acetylcholine receptors are found postsynaptically, and glial cells called Schwann cells surround the synaptic terminal. Panel B. Stages in the formation of the NMJ: 1) An isolated growth cone from a motor neuron is guided to the muscle by axon guidance cues. 2) The first contact is an unspecialized physical contact. 3) However, synaptic vesicles rapidly cluster in the axon terminal, acetylcholine receptors start to cluster under the forming synapse, and a basal lamina is deposited in the synaptic cleft. 4) As development proceeds, multiple motor neurons innervate each muscle. 5) Over time, however, all but one of the axons are eliminated through an activity-dependent process, and the remaining terminal matures.Source. Reprinted from Sanes JR, Jessell TM: "The Formation and Regeneration of Synapses," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 1087–1114. Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–18. Neurotrophins and their receptors.Neurotrophins exert their effects through binding to two types of receptors: the low-affinity nerve growth factor receptor (also called p75) and the high-affinity tyrosine kinase receptors (the Trk receptors). Nerve growth factor (NGF) binds primarily to TrkA, and brain-derived neurotrophic factor (BDNF) and neurotrophin 4/5 (NT-4,5) bind primarily to TrkB. The specificity of neurotrophin 3 (NT-3) is less precise; although it mostly binds to TrkC, it can also bind to TrkA and TrkB under some cellular contexts. In addition, all of the neurotrophins bind to p75.Source. Adapted from Jessell TM, Sanes JR: "The Generation and Survival of Nerve Cells," in Principles of Neural Science, 4th Edition. Edited by Kandel ER, Schwartz JH, Jessell TM. New York, McGraw-Hill, 2000, pp. 1041–1062. Copyright 2000, The McGraw-Hill Companies, Inc. Used with permission.

FIGURE 4–19. Ocular dominance columns in visual cortex.Panel A. In the human visual pathway, optic fibers from each eye split at the optic chiasm, half going to each side of the brain. In this schematic drawing, fibers conveying visual information from the left sides of each retina are shown projecting to the left lateral geniculate nucleus (LGN). LGN neurons (in different layers) in turn project to ipsilateral visual cortex (principally to layer 4c). In the geniculate-recipient layers of the mature visual cortex, inputs from the eyes segregate into ocular dominance (OD) columns. Panel B. Radioactive proline injections into one eye of a 2-week-old kitten uniformly label layer 4 in coronal sections of visual cortex, indicating that afferents from that eye are evenly distributed in cortex at this age. However, over the next few weeks, similar injections show a segregation of geniculate afferents into OD columns. Panel C. Schematic diagram of the formation of OD columns within layer 4 of cortex during normal development. Panel D. One eye of a normal monkey was injected with a radioactive tracer that was transported transsynaptically along the visual pathways. Cortical areas receiving inputs from the injected eye are labeled white, revealing an alternating pattern of evenly spaced stripes (section cut tangentially through layer 4c). Panel E. Monocular deprivation alters the development of OD columns. Here the tracer was injected into the nondeprived eye, revealing broader stripes and thus an expansion of the area innervated by the nondeprived eye. Thus, normal experience is a prerequisite to the correct wiring of the cortex.Source. Panel A reprinted from Kandel ER, Jessell T: "Early Experience and the Fine Tuning of Synaptic Connections," in Principles of Neural Science. Edited by Kandel ER, Schwartz JHS, Jessell TM. Stamford, CT, Appleton & Lange, 1991, pp. 945–958. Copyright 1991, The McGraw-Hill Companies, Inc. Used with permission.Panel B adapted from LeVay S, Stryker MP, Shatz CJ: "Ocular Dominance Columns and Their Development in Layer IV of the Cat's Visual Cortex: A Quantitative Study." Journal of Comparative Neurology 179:223–244, 1978. Used with permission.Panel C reprinted from Purves D, Augustine GJ, Fitzpatrick D, et al. (eds): Neuroscience. Sunderland, MA, Sinauer Associates, 1997, p. 427. Used with permission.Panels D and E reprinted from Hubel DH, Wiesel TN, LeVay S: "Plasticity of Ocular Dominance Columns in Monkey Striate Cortex." Philosophical Transactions of the Royal Society of London—Series B: Biological Sciences 278:377–409, 1977. Used with permission.
Table Reference Number

Neuropsychiatric disorders result from disordered functioning of neurons and in particular their synapses.

Neurons receive synaptic input from thousands of other neurons and in turn transmit information to thousands of other neurons.

Learning and memory involve both short- and long-term synaptic changes, characteristically induced by high-frequency activation.

Neurotransmitter receptors couple to second messenger systems that profoundly increase the range of responses a neuron shows to synaptic input, extending to changes in gene transcription.

During development, neurons and glia are generated in proliferative zones lining the ventricular system and then migrate into the overlying cortical mantle.

The determination of cell fate occurs at regional, local, and cellular levels.

Neurotransmitters themselves may have trophic or toxic roles in the shaping of neurons and their interconnections.

Neurons are initially produced in excess; their survival depends on trophic factors produced by their targets.

Normal sensory experience is essential to the maturation of neural connections.

Behaviorally relevant, temporally coincident sensory input induces changes in cortical synaptic connectivity.

In both development and learning, the NMDA receptor is the coincidence detector, requiring both neurotransmitter binding and depolarization for activation.

NMDA receptors mediate the influx of Ca2+ and trigger changes in synaptic strength and numbers.

Ca2+ regulates the growth or retraction of neurites and programmed cell death.

Adult neurogenesis may provide intrinsic mechanisms that could be harnessed for the treatment of neurodegenerative disorders.

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1.
Glial cells are divided into several classes. One type of glial cell is called an oligodendrocyte. Which of the statements below describes the primary function of oligodendrocytes?
2.
The cytoskeleton of the neuron has several filamentous components. Which of the following statements describes the microtubules, one of these filamentous components?
3.
Neurons communicate with one another at specialized sites of close membrane apposition called synapses. Some neurons convey information from one region of the brain to the other (projection neurons), whereas other neurons convey information only to neighboring neurons (local circuit interneurons). Which of the following connections describes the synapse between a presynaptic axon terminal with a postsynaptic dendrite?
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