Page 0: Page 1: LOGO Chapter 7 The Nervous System: Neurons and Synapses Page 2: Nervous System 2 types of cells in the nervous system:  Neurons.  Supporting cells. Nervous system is divided into:  Central nervous system (CNS): • Brain. • Spinal cord.  Peripheral nervous system (PNS): • Cranial nerves. • Spinal nerves. Page 3: Neurons Basic structural and functional units of the nervous system.  Cannot divide by mitosis. Respond to physical and chemical stimuli. Produce and conduct electrochemical impulses. Release chemical regulators. Nerve:  Bundle of axons located outside CNS. • Most composed of both motor and sensory fibers. Page 4: Neurons  Cell body (perikaryon):  “Nutrition center.”  Cell bodies within CNS clustered into nuclei, and in PNS in ganglia. (continued)  Dendrites:  Provide receptive area.  Transmit electrical impulses to cell body.  Axon:  Conducts impulses away from cell body.  Axoplasmic flow: • Proteins and other molecules are transported by rhythmic contractions to nerve endings.  Axonal transport: • Employs microtubules for transport. • May occur in orthograde or retrograde direction. Page 5: Neurons (continued) Page 6: Functional Classification of Neurons  Based upon direction impulses conducted.  Sensory or afferent:  Conduct impulses from sensory receptors into CNS.  Motor or efferent:  Conduct impulses out of CNS to effector organs.  Association or interneurons:  Located entirely within the CNS. Page 7: Structural Classification of Neurons Based on the # of processes that extend from cell body.  Pseudounipolar: • Short single process that branches like a T. – Sensory neurons.  Bipolar neurons: • Have 2 processes. – Retina of the eye.  Multipolar: • Have several dendrites and 1 axon. Page 8: PNS Supporting Cells Schwaan cells:  Successive wrapping of the cell membrane.  Outer surface encased in glycoprotein basement membrane.  Provide insulation. Nodes of Ranvier:  Unmyelinated areas between adjacent Schwaan cells that produce nerve impulses. Satellite cells:  Support neuron cell bodies within ganglia. Page 9: CNS Supporting Cells Oligodendrocytes:  Process occurs mostly postnatally.  Each has extensions that form myelin sheaths around several axons. • Insulation. Page 10: Nerve Regeneration Schwann cells:  Act as phagocytes, as the distal neuronal portion degenerates.  Surrounded by basement membrane, form regeneration tube: • Serve as guide for axon. • Send out chemicals that attract the growing axon. • Axon tip connected to cell body begins to grow towards destination. Page 11: Nerve Regeneration (continued)  CNS has limited ability to regenerate:  Absence of continuous basement membrane.  Oligodendrocytes molecules inhibit neuronal growth. Page 12: Neurotrophins Promote neuron growth. Nerve growth factors include:  Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), glial-derived neurotrophic factor (GDNF), neurotrophin-3, and neurotrophin-4/5. Fetus:  Embryonic development of sensory neurons and sympathetic ganglia (NGF and neurotrophin-3). Page 13: Neurotrophins Adult:  Maintenance of sympathetic ganglia (NGF).  Mature sensory neurons need for regeneration.  Required to maintain spinal neurons (GDNF).  Sustain neurons that use dopamine (GDNF). Myelin-associated inhibitory proteins:  Inhibit axon regeneration. (continued) Page 14: CNS Supporting Cells  Astrocytes:  Most abundant glial cell.  Vascular processes terminate in end-feet that surround the capillaries.  Stimulate tight junctions, contributing to blood-brain barrier.  Regulate external environment of K+ and pH.  Take up K+ from ECF, NTs released from axons, and lactic acid (convert for ATP production). • Other extensions adjacent to synapses. (continued) Page 15: CNS Supporting Cells Microglia:  Phagocytes, migratory. Ependymal cells:  Secrete CSF.  Line ventricles.  Function as neural stem cells.  Can divide and progeny differentiate. (continued) Page 16: Blood-Brain Barrier Capillaries in brain do not have pores between adjacent endothelial cells.  Joined by tight junctions. Molecules within brain capillaries moved selectively through endothelial cells by:     Diffusion. Active transport. Endocytosis. Exocytosis. Page 17: Electrical Activity of Axons All cells maintain a resting membrane potential (RMP):  Potential voltage difference across membrane. • Largely the result of negatively charged organic molecules within the cell. • Limited diffusion of positively charged inorganic ions.  Permeability of cell membrane: • Electrochemical gradients of Na+ and K+. • Na+/K+ ATPase pump. Excitability/irritability:  Ability to produce and conduct electrical impulses. Page 18: Electrical Activity of Axons  Increase in membrane permeability for specific ion can be measured by placing 2 electrodes (1 inside and 1 outside the cell).  Depolarization:  Potential difference reduced (become more positive). (continued)  Repolarization:  Return to resting membrane potential (become more negative).  Hyperpolarization:  More negative than RMP. Page 19: Ion Gating in Axons  Changes in membrane potential caused by ion flow through ion channels.  Voltage gated (VG) channels open in response to change in membrane potential.  Gated channels are part of proteins that comprise the channel. • Can be open or closed in response to change.  2 types of channels for K+: • 1 always open. • 1 closed in resting cell.  Channel for Na+: • Always closed in resting cells. – Some Na+ does leak into the cells. Page 20: Ion Gating in Axons (continued) Page 21: Action Potentials (APs) Stimulus causes depolarization to threshold. VG Na+ channels open.  Electrochemical gradient inward. • + feedback loop.  Rapid reversal in membrane potential from –70 to + 30 mV.  VG Na+ channels become inactivated. VG K+ channels open.  Electrochemical gradient outward.  - feedback loop.  Restore original RMP. Page 22: Action Potentials (APs) (continued) Page 23: Membrane Permeabilites AP is produced by an increase in Na+ permeability. After short delay, increase in K+ permeability. Page 24: Action Potentials (APs) (continued)  Depolarization and repolarization occur via diffusion, do not require active transport.  Once AP completed, Na+/K+ ATPase pump extrudes Na+, and recovers K+.  All or none:  When threshold reached, maximum potential change occurs.  Amplitude does not normally become more positive than + 30 mV because VG Na+ channels close quickly and VG K+ channels open.  Duration is the same, only open for a fixed period of time.  Coding for Stimulus Intensity:  Increased frequency of AP indicates greater stimulus strength.  Recruitment:  Stronger stimuli can activate more axons with a higher threshold. Page 25: Refractory Periods  Absolute refractory period:  Axon membrane is incapable of producing another AP.  Relative refractory period:  VG ion channel shape alters at the molecular level.  VG K+ channels are open.  Axon membrane can produce another action potential, but requires stronger stimulus. Page 26: Cable Properties of Neurons Ability of neuron to transmit charge through cytoplasm. Axon cable properties are poor:  High internal resistance.  Many charges leak out of the axon through membrane. An AP does not travel down the entire axon. Each AP is a stimulus to produce another AP in the next region of membrane with VG channels. Page 27: Conduction in an Unmyelinated Axon  Cable spread of depolarization with influx of Na+ depolarizes the adjacent region membrane, propagating the AP.  Conduction rate is slow.  AP must be produced at every fraction of micrometer. Page 28: Conduction in Myelinated Axon  Myelin prevents movement of Na+ and K+ through the membrane.  Interruption in myelin (Nodes of Ranvier) contain VG Na+ and K+ channels.  AP occurs only at the nodes.  AP at 1 node depolarizes membrane to reach threshold at next node.  Saltatory conduction (leaps).  Fast rate of conduction. Page 29: Synapse Functional connection between a neuron and another neuron or effector cell. Transmission in one direction only. Axon of first (presynaptic) to second (postsynaptic) neuron. Synaptic transmission is through a chemical gated channel. Presynaptic terminal (bouton) releases a neurotransmitter (NT). Page 30: Electrical Synapse  Impulses can be regenerated without interruption in adjacent cells.  Gap junctions:  Adjacent cells electrically coupled through a channel.  Each gap junction is composed of 12 connexin proteins.  Examples:  Smooth and cardiac muscles, brain, and glial Page 31: Chemical Synapse  Terminal bouton is separated from postsynaptic cell by synaptic cleft.  NTs are released from synaptic vesicles.  Vesicles fuse with axon membrane and NT released by exocytosis.  Amount of NTs released depends Page 32: Synaptic Transmission NT release is rapid because many vesicles form fusion-complexes at “docking site.” AP travels down axon to bouton. VG Ca2+ channels open.  Ca2+ enters bouton down concentration gradient.  Inward diffusion triggers rapid fusion of synaptic vesicles and release of NTs. Ca2+ activates calmodulin, which activates protein kinase. Protein kinase phosphorylates Page 33: Synaptic Transmission (continued) NTs are released and diffuse across synaptic cleft. NT (ligand) binds to specific receptor proteins in postsynaptic cell membrane. Chemically-regulated gated ion channels open.  EPSP: depolarization.  IPSP: hyperpolarization. Neurotransmitter inactivated to end transmission. Page 34: Chemical Synapses EPSP (excitatory postsynaptic potential):  Depolarization. IPSP (inhibitory postsynaptic potential):  Hyperpolarizatio n Page 35: Acetylcholine (ACh) as NT ACh is both an excitatory and inhibitory NT, depending on organ involved.  Causes the opening of chemical gated ion channels. Nicotinic ACh receptors:  Found in autonomic ganglia and skeletal muscle fibers. Muscarinic ACh receptors:  Found in the plasma membrane of smooth and cardiac muscle cells, and in cells of particular glands. Page 36: Ligand-Operated ACh Channels  Most direct mechanism.  Ion channel runs through receptor.  Receptor has 5 polypeptide subunits that enclose ion channel.  2 subunits contain ACh binding sites.  Channel opens when both sites bind to ACh.  Permits diffusion of Na+ into and K+ out of postsynaptic cell.  Inward flow of Na+ dominates.  Produces EPSPs. Page 37: G Protein-Operated ACh Channel  Only 1 subunit.  Ion channels are separate proteins located away from the receptors.  Binding of ACh activates alpha Gprotein subunit.  Alpha subunit dissociates.  Alpha subunit or the beta-gamma complex diffuses through membrane until it binds to ion channel, opening Page 38: Acetylcholinesterase (AChE)  Enzyme that inactivates ACh.  Present on postsynaptic membrane or immediately outside the membrane.  Prevents continued stimulation. Page 39: ACh in CNS Cholinergic neurons:  Use ACh as NT.  Axon bouton synapses with dendrites or cell body of another neuron. First VG channels are located at axon hillock. EPSPs spread by cable properties to initial segment of axon. Gradations in strength of EPSPs above threshold determine frequency of APs produced at axon hillock. Page 40: ACh in PNS Somatic motor neurons synapse with skeletal muscle fibers.  Release ACh from boutons.  Produces end-plate potential (EPSPs). Depolarization opens VG channels adjacent to end plate. Page 41: Monoamines as NT Monoamine NTs:  Epinephrine.  Norepinephrine.  Serotonin.  Dopamine. Released by exocytosis from presynaptic vesicles. Diffuse across the synaptic cleft. Interact with specific receptors in postsynaptic membrane. Page 42: Inhibition of Monoamines as NT  Reuptake of monoamines into presynaptic membrane.  Enzymatic degradation of monoamines in presynaptic membrane by MAO.  Enzymatic degradation of catecholamines in postsynaptic membrane by COMT. Page 43: Mechanism of Action  Monoamine NT do not directly open ion channels.  Act through second messenger, such as cAMP.  Binding of norepinephrine stimulates dissociation of Gprotein alpha subunit.  Alpha subunit binds to adenylate cyclase, converting ATP to Page 44: Serotonin as NT NT (derived from L-tryptophan) for neurons with cell bodies in raphe nuclei. Regulation of mood, behavior, appetite, and cerebral circulation. SSRIs (serotonin-specific reuptake inhibitors):  Inhibit reuptake and destruction of serotonin, prolonging the action of NT.  Used as an antidepressant. • Reduces appetite, treatment for anxiety, treatment for migraine headaches. Page 45: Dopamine an NT NT for neurons with cell bodies in midbrain. Axons project into:  Nigrostriatal dopamine system: • Nuerons in substantia nigra send fibers to corpus straitum. • Initiation of skeletal muscle movement. • Parkinson’s disease: degeneration of neurons in substantia nigra.  Mesolimbic dopamine system: • Neurons originate in midbrain, send axons to limbic system. • Involved in behavior and reward. • Addictive drugs: Page 46: Norepinephrine (NE) as NT NT in both PNS and CNS. PNS:  Smooth muscles, cardiac muscle and glands. • Increase in blood pressure, constriction of arteries. CNS:  General behavior. Page 47: Amino Acids as NT  Glutamic acid and aspartic acid:  Major excitatory NTs in CNS.  Glutamic acid:  NMDA receptor involved in memory storage.  Glycine:  Inhibitory, produces IPSPs.  Opening of Cl- channels in postsynaptic membrane. • Hyperpolarization.  Helps control skeletal movements.  GABA (gamma-aminobutyric acid):  Most prevalent NT in brain.  Inhibitory, produces IPSPs. • Hyperpolarizes postsynaptic membrane. – Motor functions in cerebellum. Page 48: Polypeptides as NT CCK:  Promote satiety following meals. Substance P:  Major NT in sensations of pain. Synaptic plasticity (neuromodulating effects):  Neurons can release classical NT or the polypeptide NT. Page 49: Polypeptides as NT  Endogenous opiods:  Brain produces its own analgesic endogenous morphine-like compounds, blocking the release of substance P.  Beta-endorphin, enkephalins, dynorphin.  Neuropeptide Y:  Most abundant neuropeptide in brain.  Inhibits glutamate in hippocampus.  Powerful stimulator of appetite.  NO:  Exerts its effects by stimulation of cGMP.  Macrophages release NO to helps kill bacteria.  Involved in memory and learning.  Smooth muscle relaxation. Page 50: Endogenous Cannabinoids, Carbon Monoxide Endocannabinoids:  Bind to the same receptor as THC.  Act as analgesics.  Function as retrograde NT. Carbon monoxide:  Stimulate production of cGMP within neurons.  Promotes odor adaptation in olfactory neurons.  May be involved in neuroendocrine regulation in hypothalamus. Page 51: EPSP No threshold. Decreases resting membrane potential.  Closer to threshold. Graded in magnitude. Have no refractory period. Page 52: Synaptic Integration EPSPs can summate, producing AP.  Spatial summation: • Numerous boutons converge on a single postsynaptic neuron (distance).  Temporal summation: • Successive waves of neurotransmitter release (time). Page 53: Long-Term Potentiation May favor transmission along frequently used neural pathways. Neuron is stimulated at high frequency, enhancing excitability of synapse.  Improves efficacy of synaptic transmission. Neural pathways in hippocampus use glutamate, which activates NMDA receptors.  Involved in memory and learning. Page 54: Synaptic Inhibition  Presynaptic inhibition:  Amount of excitatory NT released is decreased by effects of second neuron, whose axon makes synapses with first neuron’s axon.  Postsynaptic inhibition  (IPSPs):  No threshold.  Hyperpolarize postsynaptic membrane.  Increase membrane potential.  Can summate.  No refractory period. Page 55: