Introduction to Neurobiology

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1 Biology 240 General Zoology Introduction to Neurobiology Nervous System functions: communication of information via nerve signals integration and processing of information control of physiological and behavioral responses neurons - functional cells of the nervous system (Cajal, 1890s) - neurons are excitable cells that produce electrical signals - action potentials - neurons use electrical signals to receive and transmit information within the cell and chemical signals to communicate between cells. Structure of a Neuron DRAW NEURON HERE cell body contains the nucleus and most organelles dendrites branch from the cell body; receive signals from other neurons (input) axon (= nerve fiber) extends from cell body; conducts action potentials (output) axon hillock joins the axon to the cell body (integration area / trigger zone). axon terminals at the end of the axon form synapses to communicate with other cells. Nervous System Central Nervous System (CNS) consists of the brain and spinal cord Peripheral Nervous System (PNS) consists of: nerves - bundles of axons ganglia - groups of cell bodies located outside of the CNS sensory receptors - modified neurons or specialized cells that detect sensory stimuli Functional categories of neurons: sensory (afferent) neurons carry signals from sensory receptors to the CNS motor (efferent) neurons carry signals from the CNS to effector cells (muscles, glands) interneurons communicate information within the CNS Reflex arc - simplest neural circuit (Sherrington, early 1900s) 1. sensory receptor 2. sensory neuron. integrating center (CNS) 4. motor neuron 5. effector PNS CNS PNS STIMULUS sensory sensory integrating motor RESPONSE effector receptor neuron center neuron

2 Electrical Properties of Neurons ions -, K, Cl, Ca 2 - carry charge and electrical currents in excitable cells membrane potential - separation of and charge across the cell membrane, between the intracellular fluid (ICF) and extracellular fluid (ECF); measured in millivolts ion channels - integral membrane proteins, enable ions to pass through the membrane Neural signals are changes in membrane potential caused by movement of ions through channels. Resting membrane potential (RMP) - membrane potential of an unexcited cell - due to unequal distribution of ions between the ICF and ECF - around 70 mv (negative inside) in resting neurons Formation of the RMP 1. The sodium-potassium pump transports out and K in, which maintains concentration gradients of and K across the cell membrane. 2. K diffuses out of the cell down its concentration gradient through K leak channels. Outward movement of K leaves excess negative charge inside the cell, creating a negative electrical potential inside.. Negative potential creates an inward electrical gradient for K that opposes the concentration gradient. 4. At some potential, the electrical gradient exactly balances the concentration gradient. This point is the equilibrium potential* for K (E K 90 mv). If the membrane is only permeable to K, then the membrane potential will be equal to E K. 5. The resting membrane is slightly permeable to. Some leaks into the cell which moves the potential slightly above E K, so RMP 70 mv. *The equilibrium potential of an ion can be calculated using the Nernst Equation: E ion (60/z) log(c out /C in ) Factors that determine the membrane potential: 1) Concentration gradients of permeable ions (mostly K and ) across the membrane. [K ] in > [K ] out, E K = 90 mv [ ] out > [ ] in, E Na = 60 mv Membrane potential can be altered by changes in concentration of ions in the ECF and ICF; more permeable ions have a greater effect. 2) Relative permeability of the membrane to ions (K versus ). The membrane potential moves toward the equilibrium potential of the most permeable ion(s). The resting membrane is more permeable to K than to, so RMP is close to E K. Membrane potential changes rapidly when permeability changes due to opening or closing of specific ion channels. Neural Signals - rapid, transient changes in potential that result from movement of ions across the membrane - function to receive and transmit information within neurons - two types: graded potentials and action potentials ICF ICF 70 mv K [K ] = 150 mm [ ] = 15 mm 70 mv K ECF conc. gradient elec. gradient ECF [K ] = 5 mm [ ] = 150 mm K 2

3 Membrane Potential (mv) 1) Graded Potentials small, localized potential change occur at the cell body and dendrites spread passively and decrease in strength with distance variable size, dependent on stimulus strength can be depolarization (positive change) or hyperpolarization (negative change) from RMP. 2) Action Potential (nerve impulse) large, rapid potential change; large depolarization ( 70 0 mv) followed by repolarization formed at the axon spreads actively down the axon, does not decrease in strength constant amplitude, independent of stimulus strength Mechanism of the Action Potential (Hodgkin and Huxley, 1940s) - electrical stimulus is needed to produce an initial depolarization of the membrane - depolarization must reach threshold level (about 55 mv) in order to get an AP Three phases of the action potential: 1. Depolarization (rising) phase - voltage-gated sodium channels open (activation gate opens) moves in depolarization more channels open (positive feedback cycle). - potential peaks at about 0 mv 2. Repolarization (falling) phase - voltage-gated channels close (inactivation gate closes), entry stops - voltage-gated potassium channels open K moves out repolarization of the membrane toward RMP. Hyperpolarization (undershoot) phase - K channels stay open, continued K outflow pushes potential slightly below RMP - when voltage-gated K channels close after a few milliseconds, RMP is restored. Summa ry of Events in a n Action Potenti al K Resting potential Time (ms) K Rising phase of action potential 2 & 2. & K Falling phase of action potential

4 Properties of action potentials: threshold - stimulus must reach a certain minimum strength to form an impulse "all or none" - amplitude of an AP is constant and does not depend on stimulus strength regenerative - AP is actively regenerated along the axon and does not decrease in strength refractory period - short delay following the AP before another AP can be formed Synapses - junctions where a neuron communicates with another cell (neuron or effector cell) - most synapses are chemical synapses - information is transmitted from one neuron (the presynaptic cell) to another cell (postsynaptic cell) by a chemical neurotransmitter Parts of a synapse: 1. axon terminal of the presynaptic neuron - contains synaptic vesicles filled with neurotransmitter molecules 2. synaptic cleft - narrow gap between presynaptic and postsynaptic cell. postsynaptic membrane - contains receptors that bind to neurotransmitter molecules Binding of neurotransmitters to receptors causes chemically-gated ion channels to open in the postsynaptic membrane which alters the permeability of the membrane to specific ions (, K, or Cl - ). The resulting movements of ions causes a graded potential change called a postsynaptic potential. The neuromuscular junction is a well-studied system for synaptic transmission. - acetylcholine (ACh) is the neurotransmitter at the neuromuscular junction. Synaptic Transmission at the Neuromuscular Junction presynaptic cell 1. Action potential arrives at the presynaptic axon terminal. Ca 2 2. Voltage-gated calcium (Ca 2 ) channels open in the presynaptic membrane, allowing Ca 2 ions to enter the presynaptic cell.. Synaptic vesicles migrate to the presynaptic membrane, releasing acetylcholine (ACh) into the synaptic cleft. ACh postsynaptic cell 4. ACh molecules diffuse across the synaptic cleft and bind to ACh receptors in the postsynaptic membrane. 5. Binding of ACh to the receptors opens chemically-gated ion channels in the postsynaptic membrane that are permeable to and K ions. 6. ions move into the postsynaptic cell, causing a graded depolarization of the postsynaptic membrane (an EPSP). 7. ACh is broken down by the enzyme acetylcholinesterase; choline is transported back to the presynaptic cell (reuptake); ion channels close and membrane returns to resting state. Major neurotransmitters in the PNS and CNS acetylcholine (ACh) - neuromuscular junction, autonomic NS, CNS norepinephrine (NE) - autonomic NS, CNS glutamate - CNS dopamine - CNS serotonin - CNS 4

5 Study Questions 1. Diagram the basic structure of a neuron and show which parts of the neuron function in signal reception (input), signal processing (integration), and signal transmission (output). 2. identify the major components of the central nervous system (CNS) and peripheral nervous system (PNS).. Identify the three functional types of neurons. Diagram the components of a reflex arc and show the pathway of information flow from stimulus to response. What is the minimum number of synapses required for a simple spinal reflex such as the knee-jerk reflex? 4. Understand the ionic basis of the resting membrane potential. What is the approximate value of the RMP in an unstimulated neuron? What ion has the dominant effect on the RMP, and why dos it have a dominant effect? What ion channels are open in an unstimulated neuron? 5. Distinguish between graded potentials and action potentials. Summarize properties of each type of signal. 6. Summarize the mechanism of formation of an action potential. Distinguish between the three phases of the action potential. What specific ion channels and gates are open during the rising phase of the action potential? What gates close and what channels open during the falling phase? What causes the action potential to undershoot? 7. List four unique properties of action potentials. 8. Contrast between electrical and chemical signaling by neurons. 9. Describe the general structure and function of a chemical synapse. Summarize the steps of synaptic transmission at the neuromuscular junction. What is the neurotransmitter at the neuromuscular junction? What is the response of the postsynaptic cell to the neurotransmitter? How is the synaptic signal turned off? 5

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