Chapter 6 Neural signaling and structure of the nervous system

Section A. Neural Tissue1. Nervous system (Nervous System) Central N. -Brain and spinal cord Peripheral N.2. Neural tissue1) Nerve cell (Fig. 6-1) A. Structure (1) Soma (cell body) Contains nucleus and organelles Collection of RER and free ribosomes (Nissl bodies) (2) Dendrites Receive incoming signals (3) Axon hillock (initial segment) Trigger zone Generates electric signal (4) Axon Transmit outgoing signals (5) Axon (synaptic) terminal Send neural signal to other cells- Releasing neurotransmitters (6) Myelin Sheath (Fig. 6-2) Layered coverings of axons a. By oligodendrocytes CNS One oligodendrocyte covers multiple number of neurons b. By Schwann cells PNS One cell forms one myelin (7) Node of Ranvier Axon where no myelin sheath present Na+ channels are concentrated (8) Axonal transport (Fig.6.3) Cytoskeleton (microtubule) Motor proteins: (a) Kinesins: Anterograde movement From cell body to axon terminal Movement of nutrients, enzymes, organelles (b) Dyneins: retrograde movement From Axon terminal to cell body Movement of recycled membrane vesicles, growth factors, chemical signals Directly affects neuronal morphology, biochemistry, connectivity Sometimes provides a route for foreign substances including toxins and viruses (9) Synapse (Fig.6.4) Junctions between two neurons Presynaptic neuron vs. postsynaptic neuron Usually between axon terminal and dendrites2) Neuroglia (Fig. 6.6;Neuroglial cells) A. Functions (1) Provides a supporting framework (2) Phagocytosis B. Types of glial cells (1) Astroglia Largest and dominant neuroglia Secrete chemicals- neurotransmitters, growth factor Metabolic functions - provide glucose and remove ammonia Create a structural framework for the CNS Perform repairs in damaged neural tissues (2) Oligodendrocytes Form myelin sheaths around axons (CNS) (3) Microglia Smallest and rarest among neuroglia Phagocytic cells (4) Ependymal cells Formation of ependyma - line the central canal of the spinal cord, and ventricles of the brain Ependyma (at a certain area) produces CSF Sometimes ependyma has cillia to facilitate CSF circulation (5) Schwann cells (only at PNS) Form Sheath of Schwann (myelin) Improve impulse conduction3. Structural class of neurons (structure of neurons) 1) Multipolar neuron Many dendrites and one axon extending from the cell body All the motor neurons connecting skeletal muscles are multipolar *Multipolar interneurons Short axon Neural integration between interneurons Major type of neuron 2) Unipolar neuron Dendritic and axonal process are continuous Action potential begins from base of dendrites Most of the afferent neurons: Receptors of skin, internal organs, muscle 3) Bipolar neuron Two processes (dendritic and axonal) at either end, and soma in between afferent neurons of visual and auditory neurons Axon is relatively short4. Functional class of neurons (Fig. 6.3; Table 6.1,Fig.6.37) 1) Afferent neurons Relay sensory information to CNS Sensory receptors: Somatic and visceral sensory receptors No dendrites 2) Efferent neurons Carries motor commands to muscle and glands (effectors) (1) Somatic nervous system (SNS) Provides voluntary control over skeletal muscles (2) Visceral motor system (Autonomic nervous system: ANS) Provides involuntary regulation of smooth muscle, cardiac muscle, and glandular secretion. (3) Interneurons Connect neurons within CNS Integrator/ signal changer/ gate keeper 99% of neurons

Section B. Membrane potentials1. Definitions (Table 6.3) (Membrane) potential: Electric potential difference across plasma membrane (Fig. 6.8a) Equilibrium potential: The voltage difference across membrane due to a specific ion concentration gradientExample: K+ channel (Fig. 6.10) Resting membrane potential: Potential difference under resting (stabilized) condition (Fig. 6.8b) *K+ and Na+ quilibrium potential vs. resting potential (Fig.6.12)2. Resting membrane potential 1) Characters (1) Relative inside voltage to outside (2) No electric signal is produced (3) Na+ and K+ are major components on membrane potential (4) -40 to -90mV 2) Resting potential determining factors (Fig.6.13) (1) Specific ion concentrations by Na/K pumps Na+ : Higher outside K+: Higher inside (2) Membrane permeability Leaky K+ channels, but not on Na+ channels (3) Population of Na+ and K+ channels About 50-70% higher K+ channels than Na+ channels (4) No Cl- pump on cell membrane (only channels)(5) Proteins and phosphate compounds contribute to the negativity of inside of the cells 3) Calculation of equilibrium potential (1) Concentration of major ions of a nerve cell (Table 6.2) (2) Nernest equation *Only one ion is considered E= 60 log C0/ C1 C1: intracellular concentration of the ion C0: Extracellular concentration of the ion 60: constant value K+ equilibrium potential: -90mV Na+ equilibrium potential: +60mV (3) Goldman equation Multiple ions are considered at a time *Resting potential: -70mV 4) Cause of resting membrane potential K+ channel is chiefly permeable (leaky K+ channels) Small number of Na+ channels -About 50-70 times higher K+ channels than Na+ channels3. Graded potentials and action potentials *Important terms (Table 6.3) 1) Comparison between graded and action potentials (Table 6.4) A. Graded potential (Fig. 6.16) (1) Potential changes affect only a limited portion of the cell membrane. (2) Depolirization or hyperpolarization (3) Variable amplitude and duration (4) Decremental (Fig. 6.15) (5) No threshold or refractory period: summation is possible (6) Examples: synaptic potential, receptor potential, and pacemaker potential (7) Occurs at the gland tissues B. Action potential (1) All-or-none principle applied (2) No summation (3) Has threshold and refractory period (4) No decrease in intensity through conduction (5) Only depolarization (6) Rapid and large change in membrane potential (7) Deliver stimulus to long distance (8) "Excitability": Excitable membranes in nerve, muscle, endocrine, immune, and reproductive cells 2) Shift of potentials (Fig.6.14;action potential) Depolarize Overshoot Repolarize Hyperpolarize 3) Ionic basis of action potential (Fig. 6.19) (1) Resting potential Leaky K+ channels and some Na+ channels Close to K+ equilibrium potential Stimulation opens voltage-gated Na+ channels initiates depolarization (2) Threshold potential Permits more Na+ channels to openNa+ influx exceeds K+ effluxPositive feed back to bring in more Na+ by voltage-gated Na+ channels (3) Overshoot Membrane potential changed into positive Action potential reaches to +30mV (4) Peak of action potential Na+ channels closed by inactivation process (Fig. 6.19a) -"Hinged lid" or "ball and chain" -Involved protein has side chain of arginine, n-propylguanidinium (nPG) Voltage-gated K+ channels opened (5) RepolarizationRapid drop of action potential due to influx of K+ from opened K+ channels(6) Hyperpolarization Due to delayed closure of voltage-gated channels(7) Restoration of resting potential Na+/K+ pump*Tetrodotoxin (puffer fish), and local anesthetics (procaine, lidocaine) bind to the sodium channel blocking the passage of action potential*Threshold potential Membrane potential to which excitable membrane must be depolarized to initiate an action potentialUsually 15mV less negative than resting membrane potential *All-or-none principle (Fig. 6.21) Action potential occur maximally or not at all, but not in between Single action potential does not show intensity of stimulus*Threshold stimulus*Subthreshold potential *K+ concentration and action potential propagation (K-action potential) Hypokalemia -Lower resting membrane potential -Need stronger stimulation to propagate action potential Hyperkalemia -Increase resting membrane potential -Weak stimulation may cause propagation of action potential 4) Refractory period(1) Absolute refractory periodWhile potential stays above the threshold potential level During action potential, stimulus doesn't produce another action potentialDue to opening and inactivated voltage-gated Na+ channels(2) Relative refractory periodSecond action potential is produced with only greater stimulus than the usualDuring hyperpolarization periodDue to lingering inactivation of the Na+ channels, Increased K+ channel openings(3) Functions of refractory periodLimits the number of action potentials in a given timeRate of action potential relays intensity of stimulusUp to 100 action potentials per second 5) Action potential propagation (Fig.6.22) (a) Moves to adjacent membrane by ion flow (b) Due to rich voltage-gated Na+ channels and positive feedback of Na+ channel opening(c) Unidirectional in nerve, bidirectional in muscle(1) Velocity of action potentials -Depends on diameter of neuron and myelin sheath presence -Lager neuron propagates faster : Less resistance to local current : Higher ion movement rate in a short time (a) Unmyelinated axon Continuous conduction of action potential side by side The conduction rate is relatively slow (0.5m/sec)Action potential moves with the cable properties through the axon (b) Myelinated axon (Fig. 6.23) Saltatory conduct node to node (leap)Large and myelinated axon: 100m/sec Action potentials are occur only at the node Na+ channels are highly concentrated at the node Metabolically cost effective less energy needed for ion restoration * Demyelination Progressive destruction of myelin sheathsCaused by inflammation, axon damage, scarring of neural tissue Gradual loss of sensation and motor control Regional paralysis and numb Ex) Multiple sclerosis Optic nerve, brain, and spinal cord are affectedPartial loss of vision, problems with speech, balance, and general motorcoordination 6) Initiation of action potentials Graded potentials from receptor potential, or pacemaker potential, or synaptic potential

Section C. Synapses Definition: Anatomically specialized junction between two neurons, at which the electrical activity in one neuron influences the others1. Ways of neuronal communications (Fig. 6.24, neural circuits) 1) Conversions Many presynatic and one postsynaptic neuron Information from many source into one cell's activity Collecting information 2) Diversions One presynaptic neuron into many postsynaptic neuron One information to many pathways 3) Parallels 4) Reverberating circuit Feedback communication2. Functional anatomy of synapses 1) Electric synapse In gap junction between two neurons Direct movement of action potential to next neuron Useful when a group of muscles need to move at the same time Abundant in cardiac and smooth muscle Rare in general 2) Chemical synapse (Fig.6.25,26) A. Synaptic vesicleReleased from axon of presynatpic neuronContains neurotransmitters Exocytosis of neurotransmitters B Synaptic cleft 10 - 20 nm space between two neuron in synapses Neurotransmitter are releasedC. Vesicle docking site Fuse with synaptic vesicle D. ReceptorsLocated in postsynaptic neuronBind to neurotransmitters Open or close ion channels of postsynaptic membrane3. Mechanisms of neurotransmitter release (Fig.6.27) (1) Arrival of action potential opens Ca+ channels on axon terminal (2) Ca+ influx triggers formation of fusion complex between synaptic vesicle and presynatic membrane (vesicle docking site) Activation process(a) Released Ca+ binds to calmodulin(b) Ca+-calmodulin biding activates protein kinase(c) Protein kinase phosphorylates synapsin in vesicle membrane *During inactive state, synapsin holds vesicle to inhibit from presynaptic membrane binding.(d) Vesicle fuses with presynaptic membrane *SNARE proteins (soluble N-ethylmaleimide-sensitive-factor attachment protein receptor) -Proteins involved in neurotransmitter release (3) Exocytosis of neurotransmitter (4) Neurotransmitter binds to postsynaptic receptor proteins4. Activation of postsynaptic cell Binding of neurotransmitter and receptor changes function of ligand-gated channels 1) Fate of neurotransmittersReuptaken by active transport into presynaptic terminalDiffuse away to other areaDestroyed by cholinesterase 2) Responses of chemical synapses (Fig.6.30) (1) Excitatory chemical synapses (Fig. 6.28)Activation of receptor opens Na+ channels Produce graded potential called "Excitatory Postsynaptic Potential"(EPSP) Elevates activation threshold (2) Inhibitory chemical synapses (Fig. 6.29)Activation of receptor opens Cl- channels (or K+)Produce hyperpolarizing graded potential called "Inhibitory Postsyanptic Potential"(IPSP) Stabilize/ decrease membrane potential (3) Comparison of excitatory and inhibitory synapsees (Fig.6.32)5. Synaptic integration - Summation of graded potentials toward initiation of action potential (Fig. 6.31) Temporal summation Stimulation on the same cell with intervals Spatial summationMultiple stimulation on the same cell at different locations Initiation segment (Axon Hillock) has low threshold *Postsynaptic potentials last long time to initiate multiple action potentials6. Factors that determine synaptic strength (Table 6.5)1) Presynaptic factors(1) Availability of neurotransmitter(2) Axon terminal membrane potential(3) Calcium concentration(4) Activation of membrane receptors on presynaptic terminal a. Axo-axonic synapse (Fig. 6.33) b. Autoreceptors (negative feedback)(5) Drugs or diseases influence on presynaptic factors (Fig. 6.34) Causes a. Leakage of neurotransmitter from vesicle (exposure to enzyme) b. Increase transmitter release c. Block transmitter release d. Inhibit transmitter synthesis e. Block transmitter reuptake f. Block transmitter digesting enzyme at cleft g. Bind to postsynaptic receptors -Agonists or antagonists h. Inhibit or activate second messenger activity in postsynaptic cell2) Postsynaptic factors(1) Immediate past electrical history(2) Effects of other neurotransmitters/ modulators(3) Drugs and diseases (h of Fig. 6-34) 3) General factors(1) Area of synaptic contact(2) Enzymatic destruction of neurotransmitter(3) Geometry of diffusion path(4) Neurotransmitter reuptake7. Neurotransmitters and neuromodulators (Table 6.6) 1) Neuromodulators are, (1) Complex responses in postsynaptic cells (2) Associated with slow events (learning, development, sensory) 2) Classes of neurotransmitter/neuromodulator(1) Acetylcholine (ACh) Major neurotransmitter in PNS and brain Choline + Acetyl CoA. Synthesized from presynaptic vesicles Binds to cholinergic receptor -Nicotinic (cause of Alzheimer's disease), muscarinic receptor(2) Biogenic amines From amino acids Catecholamines -Dopamine, norepinephrine, epinephrine From tyrosine (Fig.6.35) Norepinephrine is a major neurotransmitter in PNS and CNS Adrenergic / noradrenergic fibers Roles in consciousness, mood, motivation, blood pressure regulation, and hormone release SerotoninFrom tryptophan Roles in sleep, food intake, reproductive behavior, emotional states HistamineReleased from mast cells and basophilsLocal immune responses and vasodilation (3) Amino acid transmitters Glutammate (Fig.6.36), aspartate GABA (Gama-Aminobutyric Acid), glycine (4) Neuropeptides Endogenous opioids -endorphin, dynorphins Peptide P (5) Miscellaneous NO (Nitric Oxide) -from arginine ATP

Section D. Structure of the nervous system1. Central nervous system (CNS) 1) Brain (Fig. 6.38, Table 6.7) Major divisions of the brain A. Cerebrum (Fig.6.39) Largest portion of the brain Weighs about 1200g in female and 1400g in male Brain size is related to body size no relationship with intelligence Divided into two hemispheres, connected by longitudinal fissure Center for conscious thought processes, sensations, intellectual functions, memory storage and retrieval, and complex motor patterns B. Diencephalon Part of forebrain Contains thalamus, hypothalamus, and pituitary gland A key relay zone of sensation and movement Control mechanisms for homeostatic integration (1) Thalamus Comprise about 4/5 of diencephalon Most part of the walls of the third ventricle Relay center through which sensory information passes to the cerebrum (2) Hypothalamus Located below the thalamus Floor and lateral wall of the third ventricle Neural center for hunger, thirst, and body temperature regulation Controls pituitary gland secretion Regulation of sleep, sexual desire, and emotions Secretes hormones Antidiuretic hormone (ADH) and Oxytocin through pituitary gland (3) Pituitary gland Located below the hypothalamus Connected to diencephalon body by stalk called infundiburum Divided into anterior and posterior pituitary gland Secretes pituitary hormones C. Brainstem (1) Midbrain Located above the pons and below the thalamus The uppermost part of the brainstem Process visual and auditory information Generate involuntary motor responses Maintenance of consciousness (2) Pons Rounded bulge on the underside of brain Located between midbrain and medulla oblongata Bridge connects cerebellum to the brain stem Regulates respiration (3) Medulla oblongata Segment attached to the spinal cord lowest subdivision of brain stem Passage of information from and to the brain Has group of neurons called vital centers -Vasomotor center: controls peripheral blood flow -Cardiac center: controls heart rate -Respiratory rhythmicity center: basic pace of respiratory movement D. Cerebellum Occupies the inferior and posterior aspect of the cranial cavity The second largest structure of the brain Connected with cerebrum, pons, medulla oblongata, and spinal cord Receives input from joint, tendon, and muscle receptors Participates in the coordination of movement Damage of cerebellum produces ataxia -Lack of coordination due to errors in the speed, force, and direction of movement*Limbic system (Fig. 6.40)A functional systemConsisted with frontal lobe cortex, temporal lobe, thalamus, and hypothalamus Associated with learning, emotional experience/ behavior, and endocrine functions 2) Spinal code Passage of sensory impulses to the brain and motor impulses from the brain Controls spinal reflexes A. Nomenclature of nerve fibers in spinal cordAscending sensory fiber tracts -Start with the prefix spino- and end with the name of the brain region where the spinal cord fibers first synapse (ex: spinothalamic tract) Descending motor fiber tracts -Start with a prefix denoting the brain region that give rise to the fibers and end with the suffix -spinal (ex: corticospinal tract) B. Anatomy (1) Consists of 31 segments (Fig.6.42) Cervical spinal nerves: 8 segmentsThoracic spinal nerves: 12 segments Lumbar spinal nerves: 5 segments Sacral spinal nerves: 5 segments Coccygeal nerve: 1 segments (2) Every segment has a pair of dorsal root ganglia and ventral roots (Fig.6.41) a. Dorsal root ganglia Contain cell bodies of sensory neurons Bring sensory information to the spinal cord b. Ventral roots Contain the axons of CNS motor neurons Control muscles and glands c. Spinal nerve Mixed nerve -Dorsal and ventral roots united (3) Spinal cord runs up to L2 (4) Cauda equina Contains long ventral and dorsal roots inferior to tip of spinal cord2. Peripheral nervous system (PNS) 1) Consists with cranial nerves and spinal nerves (1) Cranial nerve (Cranial N; Table 6.8) Arising from the brain 12 pairs Mixed nerves of sensory and motor fibers (2) Spinal nerves (Spinal N A, B) Arising from the spinal cord 31 pairs Mixed nerves of sensory and motor fibers 2) Divisions of peripheral nervous system (Table 6.9) A. Afferent division Sensory input to CNS B. Efferent division (Fig.6.43) Signal from CNS to effectors Neurotransmitters (Fig.6.46) -First neurotransmitter from the nerve exiting CNS is always Ach. (1) Somatic division Signal to skeletal muscle Leads to muscle contraction (2) Autonomic division (Fig. 6.44) Signal to glands, cardiac and smooth muscle, and gastrointestinal tract Excitatory or inhibitory Examples of autonomic nervous systems activity (Table 6.11) a. Sympathetic pathway "Fight-or-flight" Nerves from thoracolumbar division b. Parasympathetic pathway "Rest-or-digest" Nerves from brain and sacrum (craniosacral division)3. Blood Brain barrier 1) Function Protects from harmful substances through blood including pathogens2) Formation -Form a tight junction among, Endothelial cells Astrocytes' secretion (determines permeability) Basement membrane of blood vessels 3) Permeability of the barrier a) Type of substance transport Facilitated diffusion: creatinine, urea, ions... Active transport: glucose, proteins b) Lipid-soluble substances move freely Oxygen, carbon dioxide, alcohol, caffeine... c) Protein and antibiotics are carried by transporters4. Cerebrospinal fluid (CSF) 1) Functions (1) Physical protection of brain and spinal cord (2) Chemical protection Maintains ionic balance (3) Exchange of nutrients and wastes 2) Ventricles (Fig.6.47) CSF containing cavities in brain Four ventricles-Two lateral ventricles -Third ventricle -Forth ventricle 3) CSF production From choroid plexuses of ventricles -Network of capillaries in the walls of ventricles Filtration of plasma and secretion through ependymal cells 4) Circulation of CSF (subarachnoid space) Openings in the roof of fourth ventricle Subarachnoid space contains CSF Reabsorption of CSF into blood -Through arachnoid villi at suprior sagital sinus Active circulation -Forces from production of CSF -Circulatory, respiratory, and postural pressures