NERVOUS SYSTEM The master controlling and communicating system of the body --- cells communicate via electrical and chemical signals. Signals are rapid, specific and cause almost immediate responses. Functions include: 1. Sensory Input sensory receptors monitor changes occurring inside and outside the body. 2. Integration process & interprets sensory input and makes decisions about what to do 3. Motor Output response that activates muscles or glands (effector organs) Organization of Nervous System 2 subdivisions: Central Nervous (CNS) consist of the brain and spinal cord. The function is integration. Peripheral Nervous (PNS) consist of nerves extending from the brain and spinal cord to the body. The functions are sensory input and motor output. The PNS is further divided into: Afferent or Sensory Division Efferent or Motor Division Somatic Sensory Fibers - transmit impulses from the skin, skeletal muscles & joints to the CNS Visceral Sensory Fibers - transmit impulses from visceral organs to the CNS Somatic (SNS) Fibers - transmit impulses from CNS to control voluntary action of skeletal muscle Nervous Tissue neuroglia & neurons NEUROGLIA cells insulate, support & protect; cells are unable to transmit impulses and never lose the ability to mitotically divide Autonomic (ANS) Fibers - transmit impulses from CNS to regulate involuntary actions of smooth muscle, cardiac muscle & glands Is further divided into: Sympathetic regulates actions in stressful situations Parasympathetic regulates actions during rest Astrocyte cells cells in the CNS that contain projections that cling to neurons bracing them and anchoring them to capillaries; serves as a barrier and medium for diffusion between capillaries and neurons. Most abundant, versatile and highly branched glial cells --- controls chemical environment around neuron and guides migration of young neurons. Microglia cells phagocyte cells in the CNS that dispose of debris including dead brain cells and bacteria; needed because the immune system is denied access to CNS Ependymal cells cells line cavities of the brain and spinal cord; the beating of their cilia helps to circulate cerebrospinal fluid and forms a protective cushion around CNS Oligodendrocytes cells wrap their extensions tightly around nerve fibers in the CNS producing fatty insulating coverings called myelin sheaths 1
Schwann cells cells form the myelin sheaths of neurons in PNS Satellite cells cells protect & cushion neurons in PNS NEURONS (in CNS and PNS) cells that conduct impulses; exhibit extreme longevity can live 100 years or more. They are amitotic and have a high metabolic rate require continuous supply of oxygen and glucose. Neuron Anatomy - Soma (Cell Body or Perikaryon): metabolic center that contains the nucleus. Clusters of cell bodies in the CNS are called nuclei and clusters of cell bodies in PNS are called ganglia. Processes extend from the cell body of all neurons the dendrites and axons. Bundles of processes are tracts in the CNS and nerves in the PNS. Dendrite: slender fiber extensions containing sensory receptors that conduct impulse toward soma (graded potentials short distance signals) Axon: single fiber extension that generate nerve impulses and conducts impulses away from soma. Transmit impulses along axolemma (cell membrane) to axon terminal (secretory region). Initial region of axon arises from area of cell body called axon hillock. In motor neurons, the nerve impulse is generated at the junction of the axon hillock and the axon. In some neurons, the axon is short or absent; in others it is long (up to 3-4 feet). Long axons are called nerve fibers. Axons occasionally branch forming axon collaterals. Axons branch forming terminal branches at the distal end of terminal branches are axon terminals (synaptic knobs). Contains same organelles found in dendrites and cell bodies except the Nissl bodies (Rough ER) and the Golgi structures involved in protein synthesis and packaging. Axons rely on cell body for necessary proteins and on distribution. Axon terminal: end branches of axon terminal branches that contain neurotransmitter storage vesicles; neurotransmitters either excite or inhibit neurons. Myelin: white, fatty material that protects and insulates fibers; speeds up impulse transmission. Nodes of Ranvier: gaps between myelin sheaths Synapse: junction of two neurons; space at synapse is called synaptic cleft 2
Types of Neurons Structural Classification: Multipolar Bipolar Unipolar Most abundant in body. Rare found in some Found mainly in PNS. Major neuron type in CNS. special sensory organs Common in dorsal root ganglia of Many processes extend (olfactory mucosa, eye, ear) spinal cord and sensory ganglia from the cell body all are Have two processes of cranial nerves. dendrites except for single dendrite and axon. One short process extends from axon. cell body and forms central and peripheral processes these form the axon. Types of Neurons Functional Classification: 1. Sensory or Afferent neurons (mostly unipolar) carries impulse from sensory receptors on dendrite endings to CNS; cell bodies in ganglia in PNS 2. Interneurons or Mixed neurons (multipolar) connect motor and sensory neurons in spinal cord; transmit impulse to and from brain 3. Motor or Efferent neurons (multipolar) carries impulse from CNS to effector organ; impulse brings about motor response. Most cell bodies in CNS. NEURON PHYSIOLOGY Neurons are highly irritable (responsive to stimuli). When a neuron is adequately stimulated, an electrical impulse is generated and conducted along the axon. The action potential (nerve impulse) is always the same. The body is electrically neutral same number of positive and negative charges. 1. Plasma membrane of a resting (inactive) neuron is polarized, which means the outside of cell is more positive than the inside. All gated Na + and K + channels are closed only leakage channels for Na + and K + are open. This maintains the resting membrane potential. 3
Membrane potential changes when concentrations of ions across membrane change OR membrane permeability to ions changes Changes produce two types signals: Graded potentials (signals only over short distances) and Action potentials (long distance signals of axons) Changes in membrane potential used as signals to receive, integrate, and send information 2. Graded Potentials - short-lived, localized change in membrane potential in response to a stimulus; either depolarization or hyperpolarization occurs. Triggered by stimulus that opens gated ion channels current flows, but dissipates quickly. Graded potentials occur in cell bodies and dendrites. Light, heat, mechanical pressure and chemicals (such as neurotransmitters) are stimuli that may generate a graded potential. 3. At the axon, stimulus changes permeability of membrane and Na+ diffuse into cell to change polarity this is called depolarization (inside is more positive). For axon to fire, depolarization must meet threshold. If the stimulus is strong enough, additional Na+ gates open, increasing flow of Na+ --- causing an action potential. Action potential travels down the length of the axon as opened Na+ gates stimulate neighboring Na+ gates to open. The action potential is all-or-nothing. When the stimulus fails to produce depolarization that exceeds threshold, no action potential results. When threshold potential is exceeded, complete depolarization occurs. 4. Action potential is created impulse travels through neuron jumping from node to node 5. In response to the inflow of Na+, K+ channels open and K+ diffuses out of cell to restore the electrical conditions this is called repolarization. Soon after the K+ gates open, the Na+ gates close. Repolarization must occur to conduct another impulse. 6. Na/K pump uses ATP to restore the initial concentrations of Na & K to resting ionic conditions refractory period. 7. These events continue to spread across the membrane of the neuron until the impulse reaches the axon terminal. 8. At axon terminal, impulse causes Ca ions to enter cell triggering vesicles to release neurotransmitters 9. Neurotransmitters bind to receptors on dendrite of next neuron process occurs again on next neuron. 4
Conduction Velocity Fibers that transmit impulses rapidly are found in neural pathways where speed is essential. Axons that conduct impulses more slowly typically serve internal organs. The rate of the impulse propagation depends on: 1. Axon diameter large diameter fibers have less resistance to local current flow so the faster it conducts impulses. 2. Degree of myelination continuous conduction in nonmyelinated axons is slower than saltatory conduction in myelinated axons. Myelin sheaths insulate and prevent leakage of charge. Saltatory conduction (possible only in myelinated axons) is about 30 times faster Voltage-gated Na + channels are located at myelin sheath gaps Action potentials are generated only at gaps. Electrical signal appears to jump rapidly from gap to gap Multiple Sclerosis (MS) autoimmune disease in which immune system attacks myelin sheaths in CNS are destroyed and myelin turns to hardened lesions called scleroses. Impulse conduction is slow and eventually ceases. Demyelinated axons increase Na+ channels causing cycles of relapse and remission. Nerve Fiber Classification Group A fibers - large diameter, myelinated somatic sensory and motor fibers of skin, skeletal muscles, joints; transmit at 150 m/s. Group B fibers intermediate diameter, lightly myelinated fibers; transmit at 15 m/s Group C fibers - smallest diameter, unmyelinated ANS fibers; transmit at 1 m/s Synapses Axodendritic - between axon terminals of one neuron and dendrites of others Axosomatic - between axon terminals of one neuron and soma of others Less common types --- Axoaxonal (axon to axon), Dendrodendritic (dendrite to dendrite), Somatodendritic (dendrite to soma) Electrical Synapses neurons electrically coupled (joined by gap junctions that connect cytoplasm of adjacent neurons); less common than chemical synapse. Transmission across these synapses are very rapid communication can be unidirectional or bidirectional. Electrical synapses provide a simple means of synchronizing the activity of all interconnected neurons. Most abundant in embryonic nervous tissue. As the nervous system develops, some electrical synapses are replaced by chemical synapses. Chemical Synapses specialized for release and reception of chemical neurotransmitters. Composed of two parts axon terminal of presynaptic neuron (contains synaptic vesicles filled with neurotransmitters) & neurotransmitter receptor on postsynaptic neuron s membrane (usually on dendrite or cell body) Two parts separated by synaptic cleft a fluid filled space; electrical impulse changes to chemical across the synapse, then back to electrical. 5
Synaptic Cleft space between the presynaptic neuron and the postsynaptic neuron; prevents nerve impulses from directly passing from one neuron to next Transmission across synaptic cleft is a chemical action; depends on release, diffusion and receptor binding of neurotransmitters. Ensures unidirectional communication between neurons Information transfer across chemical synapse - 1. Action Potential (AP) arrives at axon terminal of presynaptic neuron 2. Causes voltage-gated Ca 2+ channels to open -- Ca 2+ floods into cell 3. Synaptotagmin protein binds Ca 2+ and promotes fusion of synaptic vesicles with axon membrane --- Exocytosis of neurotransmitter into synaptic cleft occurs o Higher impulse frequency more released 4. Neurotransmitter diffuses across synapse -- Binds to receptors on postsynaptic neuron 5. Ion channels are opened --- Causes an excitatory or inhibitory event (graded potential) 6. Neurotransmitter effects terminated --- within a few milliseconds neurotransmitter effect terminated in one of three ways: reuptake (by astrocytes or axon terminal), degradation (by enzymes, diffusion (away from synaptic cleft) Synaptic delay is a rate-limiting step of neural transmission --- Time needed for neurotransmitter to be released, diffuse across synapse, and bind to receptors. Neurotransmitter receptors cause graded potentials that vary in strength due to amount of neurotransmitter released and time neurotransmitter stays in area. 6
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Postsynaptic Potentials & Synaptic Integration Types of postsynaptic potentials: EPSP (excitatory postsynaptic potentials) and IPSP (inhibitory postsynaptic potentials) Excitatory synapses & EPSPs an EPSP is a local depolarization of the postsynaptic membrane that brings the neuron closer to action potential threshold. Neurotransmitter binding opens chemically gated channels Allows simultaneous flow of Na + and K + in opposite directions Na + influx greater than K + efflux net depolarization called EPSP (not AP) EPSP help trigger AP if EPSP is of threshold strength Can spread to axon hillock, trigger opening of voltage-gated channels, and cause AP to be generated Inhibitory synapses & IPSPs - is a local hyperpolarization of the postsynaptic membrane that drives the neuron away from AP threshold. Reduces postsynaptic neuron's ability to produce an action potential Makes membrane more permeable to K + or Cl o If K + channels open, it moves out of cell o If Cl - channels open, it moves into cell Therefore neurotransmitter hyperpolarizes cell --- inner surface of membrane becomes more negative & AP is less likely to be generated Synaptic Integration Summation A single EPSP cannot induce an AP -- EPSPs can summate to influence postsynaptic neuron & IPSPs can also summate Most neurons receive both excitatory and inhibitory inputs from thousands of other neurons - -- Only if EPSP's predominate and bring to threshold AP Two types of summation: temporal summation (one or more presynaptic neurons transmit impulses in rapid-fire order) and spatial summation (postsynaptic neuron is stimulated simultaneously by large number of terminals at same time 8
Integration Synaptic Potentiation Repeated use of synapse increases ability of presynaptic cell to excite postsynaptic neuron Ca 2+ concentration increases in presynaptic terminal and postsynaptic neuron Brief high-frequency stimulation partially depolarizes postsynaptic neuron Chemically gated channels (NMDA receptors) allow Ca 2+ entry Ca 2+ activates kinase enzymes that promote more effective responses to subsequent stimuli Integration Presynaptic Inhibition When the release of an excitatory neurotransmitter by one neuron is inhibited by the activity of another neuron via an axoaxonal synapse End result --- less neurotransmitter released & smaller EPSPs formed Neurotransmitters Each neuron communicates with others to process and send messages to the rest of the body through neurotransmitters. Most neurons make two or more neurotransmitters and neurons can exert several influences. Neurotransmitters are usually released at different stimulation frequencies and are classified by chemical structure and function. There are 50 or more neurotransmitters identified. Classification of neurotransmitters based on effect (excitatory vs. inhibitory) and action (direct vs. indirect) 1. Excitatory vs. Inhibitory - neurotransmitter effects can be excitatory (depolarizing) and/or inhibitory (hyperpolarizing) effect determined by receptor to which it binds 2. Direct vs. Indirect a) Direct action - neurotransmitter binds to and opens ion channels promotes rapid responses by altering membrane potential b) Indirect action - neurotransmitter acts through intracellular second messengers, usually G protein pathways; broader, longer-lasting effects similar to hormones Neurotransmitters Acetylcholine stimulates muscle contractions, causes glands to secrete hormones and plays a role in memory. (Alzheimer s disease is associated with a shortage of Ach.) ACh excitatory at neuromuscular junctions in skeletal muscle, but inhibitory in cardiac muscle. Dopamine controls mood and motivation. Drives our internal feelings of reward and pleasure. It has an important role in learning. (Drugs such as cocaine and alcohol increase the levels of dopamine. Schizophrenia is associated with increased levels of dopamine. Parkinson s disease is associated with decreased levels of dopamine.) GABA (gamma-aminobutyric acid) an inhibitory neurotransmitter because it causes cells to be less excitable. (Low levels of GABA cause anxiety disorders.) Serotonin an inhibitory neurotransmitter involved in mood and emotion. It brings about a sense of emotional well-being and helps to regulate sleep. (Low levels lead to depression and trouble sleeping. Interesting fact: Warm milk before bedtime increases the levels of serotonin.) Norepinephrine is released to stimulate our sympathetic nervous system and put our body into high alert. It s important in forming memories. (Exercise increases the release of norepinephrine and stress decreases it.) Glutamate an excitatory neurotransmitter which plays a role in memory. (Excessive amounts of glutamate due to a stroke or brain damage will kill neurons. ALS results from excessive glutamate production.) 9
Endorphins an inhibitory neurotransmitter involved in pain reduction and pleasure. Gasotransmitters - Nitric oxide (NO), carbon monoxide (CO), hydrogen sulfide gases (H 2 S) 1. Bind with G protein coupled receptors in the brain 2. Synthesized on demand 3. Nitric oxide involved in learning and formation of new memories; brain damage in stroke patients, smooth muscle relaxation in intestine Neurotransmitter Receptors Channel-linked receptors ligandgated ion channels that mediate fast synaptic transmission Excitatory receptors are channels for small cations -- Na + influx contributes most to depolarization Inhibitory receptors allow Cl influx that causes hyperpolarization G protein-linked receptors responses are indirect, complex, slow, and often prolonged; involves transmembrane protein complexes; cause widespread metabolic changes Neurotransmitter binds to G protein linked receptor G protein is activated activated G protein controls production of second messengers Second messengers - Open or close ion channels; Activate kinase enzymes; Phosphorylate channel proteins; Activate genes and induce protein synthesis 10
Neural Integration Neurons function in groups which contribute to broader neural functions Millions of neurons in the CNS are organized in neuronal pools, functional groups of neurons that integrate incoming information received from receptors or different neuronal pools and then forward the processed information to other destinations. In a simple neuronal pool, a single presynaptic fiber branches and synapses with several neurons in pool. Discharge zone - neurons most closely associated with incoming fiber. Facilitated zone - neurons farther away from incoming fiber Circuits - patterns of synaptic connections in neuronal pools Diverging circuit - one input, many outputs; an amplifying circuit Example: A single neuron in the brain can activate 100 or more motor neurons in the spinal cord and thousands of skeletal muscle fibers Converging circuit - many inputs, one output; a concentrating circuit Example: Different sensory stimuli can all elicit the same memory Reverberating circuit - signal travels through a chain of neurons, each feeding back to previous neurons; an oscillating circuit -- controls rhythmic activity Example: Involved in breathing, sleep-wake cycle, and repetitive motor activities such as walking Parallel after-discharge circuit signal stimulates neurons arranged in parallel arrays that eventually converge on a single output cell; Impulses reach output cell at different times, causing a burst of impulses called an after-discharge Example: May be involved in exacting mental processes such as mathematical calculations Patterns of Neural Processing Serial Processing input travels along one pathway to a specific destination; system works in all-or-none manner to produce specific, anticipated response Example: spinal reflexes rapid, automatic responses to stimuli; particular stimulus always causes same response; occur over pathways called reflex arcs Parallel Processing input travels along several pathways; different parts of circuitry deal simultaneously with the information; one stimulus promotes numerous responses Important for higher-level mental functioning Example: a sensed smell may remind one of an odor and any associated experiences 11
Developmental Aspects of Neurons Nervous system originates from neural tube and neural crest formed from ectoderm. The neural tube becomes CNS. Neuroepithelial cells of neural tube proliferate to form number of cells needed for development Neuroblasts become amitotic and migrate Neuroblasts sprout axons to connect with targets and become neurons Axonal Growth the growth cone is the growing tip of an axon that gives an axon the ability to interact with its environment. Cell surface adhesion proteins provide anchor points for the growth cone Neurotropins that attract or repel the growth cone Nerve growth factor (NGF) must be present to keeps neuroblast alive during the growth and development once growth cone finds target, it must find right place to form synapse --- Astrocytes provide physical support and cholesterol essential for construction of synapses. Cell Death - about 2/3 of neurons die before birth if they do not form synapse with target cells; many cells also die due to apoptosis (programmed cell death) during development 12