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Outline Week 4 - The Nervous System: Neurons and Synapses Neurons Neuron structures Types of neurons Electrical activity of neurons Depolarization, repolarization, hyperpolarization Synapses Release of neurotransmitter Synaptic potentials: EPSPs and IPSPs Examples of neurotransmitters Copyright The McGraw-Hill Companies, Inc. Permission required for reproduction or display. No figures are included in this lecture note. Nervous System Nervous system is divided into: Central nervous system (CNS) Brain Spinal cord Peripheral Nervous System (PNS) Cranial nerves ( 뇌신경 ) Spinal nerves ( 척수신경 ) Two types of cells in the nervous system: Neurons: conduct electrical signals Neuroglial cells: support neurons Neuron Structure Cell Body Nucleus and typical organelles Dendrites Receive stimulation Axon Conduct electrical signals (action potentials) Often insulated with a myelin sheath Axon hillock site where AP s originate Axon terminals where chemical signals are released

Functional Classification of Neurons Sensory (or afferent) Neurons Conduct electrical signals from sensor receptors into CNS Motor (or efferent) Neurons Conduct electrical signals out of CNS to effector organs (muscle or glands) Association Neurons (or interneurons) Located entirely within the CNS. Serve an integrative function. Structural Classification of Neurons Pseudounipolar (most sensory neurons) Cell body sits along side of single process Bipolar (sensory neurons in eyes and ears) Dendrite and axon arise from the opposite ends of cell body. Multipolar (motor and association neurons) Many processes extend from cell body Many dendrites and a single axon Neuroglial Cells Cells that are non-conducting but support neurons Two types are found in the PNS: Schwann cells( 슈반세포 ): form myelin sheaths around the axons of PNS neurons Satellite cells( 위성세포 ): support cell bodies within the ganglia of the PNS Neuroglial Cells CNS has oligodendrocytes, microglia, astrocytes and ependymal cells. Oligodendrocytes( 희소돌기세포 ): form myelin sheaths around the exons of CNS neurons Astrocytes( 성상세포 ) Control permeability of capillaries in CNS (blood brain barrier) Support neuronal activity Microglia( 미세아교세포 ) Engulf foreign / degenerated material Ependymal cells( 뇌실막세포 ) form epithelial lining of brain and spinal cord cavities

Myelination Myelin sheath Schwann cells in PNS and oligodendrocytes in CNS form myelin sheath. Electrically insulates axon Accelerates electric signal transmission Electrical Activity of Neurons Node of Ranvier Gaps in the myelin sheath. Serve a very important function in the conduction of impulses by myelinated axons. Resting Membrane Potential Neurons have a resting membrane potential of 70mV. Established by large negative molecules inside the cell Na + /K + pumps Permeability of the membrane to ions At rest, there is a high concentration of K + inside the cell and Na + outside the cell. Changes in Membrane Potential At rest, a neuron is considered polarized when the inside is more negative than the outside. When the membrane potential inside the cell increases, this is called depolarization. A return to resting potential is called repolarization. When the membrane potential inside the cell decreases, this is called hyperpolarization.

Changes in Membrane Potential Depolarization occurs when positive ions enter the cell (usually Na + ). Hyperpolarization occurs when positive ions leave the cell (usually K + ) or negative ions (Cl ) enter the cell. Depolarization of the cell is excitatory. Hyperpolarization is inhibitory. Voltage-Gated Channels Found in axons Axon hillock must be depolarized to the threshold potential for voltagegated channels to open If membrane is depolarized to threshold, a cycle of activation (channel opening) followed by inactivation (closing) ensues Action Potentials At threshold membrane potential ( 55mV), voltage-gated Na + channels open, and Na + rushes in. As the cell depolarizes, more Na + channels are open, and the cell becomes more and more permeable to Na +. This is a positive feedback loop. Membrane potential reaches +30mV. This is called the action potential. Action Potentials At +30mV, Na + channels close, and K + channels open. Results in repolarization of membrane potential When membrane potential drops below threshold, K + channels close Repolarization actually overshoots resting potential and gets down to 85mV. This is called hyperpolarization. Na + /K + pumps quickly reestablish resting potential.

Figures 1. Depolarization of an axon affects Na + and K + diffusion in sequence 2. Membrane potential changes caused by ion movements Refractory Periods There is a refractory period after an action potential when the neuron cannot become excited again. The absolute refractory period occurs during the action potential. Na + channels are inactive. The relative refractory period is when K + channels are still open. Only a very strong stimulus can overcome this. All-or-None Law Once threshold has been reached, action potential will happen. The size of the stimulus will not affect the size of the action potential; it will always reach +30mV. Coding for Stimulus Intensity Differences in stimulus intensity are detected by the frequency of action potential generation. A stronger stimulus will make action potentials occur more frequently.

Conduction of Nerve Impulses When an action potential occurs at a given point on a neuron membrane, voltage- gated Na + channels open as a wave down the length of the axon. Action Potential Propagation Action potentials are regenerated at each segment of the axon Na + moving into one segment of the neuron during the depolarization phase quickly moves laterally inside the cell Depolarizes adjacent segment to threshold, triggering an AP at the segment Action Potential Propagation: Myelinated Axons Myelination limits sites where an action potential occurs to the nodes of Ranvier Na + entering at node quickly passes to next node, bringing it to threshold Saltatory conduction Action potential jump from one node to the next AP conduction speed Synapses

Synapse Communication junction between a neuron and either another neuron or a muscle or gland cell Chemical signals (neurotransmitters) released from axon terminal and bind to receptors on adjacent cell Stimulates physiological change (usually change in membrane potential) in the recipient cell Anatomy of a Synapse Presynaptic neuron Axon terminals contain synaptic vesicles filled with neurotransmitter Synaptic cleft Narrow space between cells Postsynaptic cell Contains receptor proteins that will bind neurotransmitter Release of Neurotransmitter Many voltage-gated Ca 2+ channels in the plasma membrane at the axon terminals AP triggers opening Ca 2+ channels Ca 2+ rushes in Ca 2+ induce exocytosis of synaptic vesicles Neurotransmitter diffuses across synaptic cleft and binds to receptors on postsynaptic cell membrane Action of Neurotransmitter Neurotransmitter diffuses across the synapse, where it binds to a specific receptor protein. The neurotransmitter is referred to as the ligand. This results in the opening of ligand-gated ion channels (also called chemically regulated ion channels).

Chemical Synapse Function Specific ligand-gated ion channels in postsynaptic cell membrane open Ions exchanged across postsynaptic cell plasma membrane Induces a synaptic potential (electrical signal) in postsynaptic cell Two Types of Synaptic Potentials: EPSPs and IPSPs Excitatory postsynaptic potential (EPSP) Postsynaptic cell membrane depolarizes Inhibitory postsynaptic potential (IPSP) Postsynaptic cell membrane hyperpolarizes If an EPSP is a strong enough depolarization to reach threshold Action potential forms in postsynaptic cell Two Types of Synaptic Potentials: EPSPs and IPSPs When ligand-gated ion channels open, the membrane potential changes depending on which ion channel is open. Opening Na + or Ca 2+ channels results in a graded depolarization (EPSP). Opening K + or Cl channels results in a graded hyperpolarization (IPSP). Characteristics of Synaptic Potentials 1. Decrease in amplitude with distance The change in membrane potential decreases the further the distance from the chemical synapse 2. Graded responses More neurotransmitter causes greater changes in membrane potential 3. Can summate No refractory period for synaptic potentials EPSPs and IPSPs generated in close succession can have an additive effect on the membrane potential of the postsynaptic cell Aspects of summation a) Spatial summation summation due to release of neurotransmitter from multiple presynaptic neurons b) Temporal summation summation due to high rate of neurotransmitter release from a presynaptic neuron

Figures The sequence of events in synaptic transmission Examples of Neurotransmitters Acetylcholine (ACh) Released by many diverse neurons Generates EPSPs or IPSPs depending on ACh receptors in the postsynaptic membranes of different cells. E.g., Nicotinic ACh Receptors Found in certain brain regions, skeletal muscle cells, and cell bodies of autonomic motor neurons in ganglia Receptor is a ligand-gated ion channel activated by the direct binding of ACh Channel opens, Na + flows into cell quickly, K + flows out slowly Induces EPSPs Acetylcholine (ACh) E.g. Muscarinic ACh Receptors Found in some CNS neurons, smooth muscle, glands, and cardiac muscle Receptor for ACh (G-protein linked receptor) is separate from the ion channel ACh binding induces activation of G-proteins in plasma membrane G-protein dissociates into α and βγ subunits G-proteins activate enzymes and channels specific to the cell E.g., generates EPSPs (by closing K + channels) in smooth muscle in digestive tract E.g., generates IPSPs (by opening K + channels) in cardiac muscle

Acetylcholinesterase (AChE) AChE is an enzyme that inactivates ACh activity shortly after it binds to the receptor. Hydrolyzes ACh into acetate and choline, which are taken back into the presynaptic cell for reuse. GABA (gamma-aminobutyric acid) Important inhibitory neurotransmitter in the CNS Binds directly to ligand-gated Cl - channels Cl - flows into cell Induces IPSPs Figures 1. Nicotinic ACh receptors 2. Muscarinic ACh receptors 3. Acetylcholinesterase 4. Gamma-aminobutyric acid (GABA)