Ns5 Synaptic Transmission


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Lecture 5 of 63 in the Neuroscience Module

"Synaptic Transmission" [Physiology]

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Ns5 Synaptic Transmission

  1. 1. NS5 – SYNAPTIC TRANSMISSION NS5 – SYNAPTIC TRANSMISSION I. OVERVIEW A. SYNAPTIC TRANSMISSION: mechanism of neuron-neuron or neuron-muscle/gland communication. B. DESCRIPTION: neurons sense changes in the environment, communicate with each other, and other tissues and organs using electrical and chemical signals 1. ELECTRICAL SIGNALS: change in membrane potential a. GRADED POTENTIAL: small currents that are generated in response to stimuli and travel short distances. They may either dissipate or summate to generate an action potential. i. GENERATOR POTENTIALS are caused by energy (heat, light etc) . ii. RECEPTOR POTENTIALS are caused by energy (heat, light etc). iii. POST-SYNAPTIC POTENTIALS are caused by chemicals. b. ACTION POTENTIAL: a brief pulse of electrical current that travels along an axon and triggers neurotransmitter release at the axon terminal. 2. CHEMICAL SIGNALS: neurotransmitters and receptors II. REVIEW A. PRINCIPLES OF ELECTRICITY 1. VOLTAGE (V): measure of potential energy; millivolts 2. POTENTIAL: difference in voltage 3. CURRENT (I): flow of electrical charge; milliamps 4. RESISTANCE (R): block or hindrance to electrical flow; ohms 5. OHM'S LAW: V = I/R B. MEMBRANE POTENTIAL 1. Definition: difference in voltage across membranes that is created and maintained by a. a concentration gradient of ions Table 1: Concentration of key ions involved in resting membrane potential concentration flow concentration ion inside cell outside cell (mM) (mM) diffuses into cell via passive channel Na+ 150 15 pumped out of cell via Na+/K+ pump diffuse out of cell K+ 5 150 pumped into cell via Na+/K+ pump requires gated channel for transport Cl- 120 10 too large to diffuse out of cell A- (proteins) 0.2 100 b. the selective permeability of the membrane to ions via ion channels 2. Useful link with animation http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/animation2.html 1
  2. 2. NS5 – SYNAPTIC TRANSMISSION C. MEMBRANE ION CHANNELS 1. Function: regulate movement of ions into and out of cell. 2. Types a. PASSIVE or LEAKAGE CHANNELS b. ACTIVE or GATED i. Ligand-gated (chemical) ii. Voltage-gated iii. Mechanically-gated D. CHANGE IN RESTING MEMBRANE POTENTIAL: 1. Causes a. change in membrane permeability b. change in ion concentrations 2. Types a. DEPOLARIZATION – membrane potential becomes less negative compared to resting potential b. HYPERPOLARIZATION – membrane potential becomes more negative compared to resting potential III. SYNAPSES A. Definition: The junction between two neurons or a neuron and an effector cell. The transmitting cell is identified as the presynaptic neuron and the receiving cell is identified as the postsynaptic neuron/cell. B. Types 1. ELECTRICAL SYNAPSE: a. Definition: an intercellular junction between two cells formed by integral membrane proteins that span the membranes of both cells to form a hydrophilic channel, 2nm in diameter; also called gap junction. b. Characteristics: i. Membranes of both cells are touching each other. ii. Junctions are usually between soma, axons and dendrites c. Function: i. permits unimpeded flow of ions and small solutes (glucose, nucleotides) between cells ii. permits synchronization d. Structural features: Junctions are formed by 2-hexamers of proteins called connexins e. Distribution: skin, smooth muscle, cardiac muscle, retina, hippocampal neurons, cerebellar neurons, GABA interneurons of neocortex, thalamus f. disease: deafness, polyneuropathy, cataracts, skin disorders, cardiovascular disorders 2. CHEMICAL SYNAPSE: a. Definition: the junction between two nerve cells from which a chemical signal is transmitted from the presynaptic neuron and is received by a receptor/ligand or chemically-gated channel on the postsynaptic membrane. 2
  3. 3. NS5 – SYNAPTIC TRANSMISSION III. SYNAPSES 2. CHEMICAL SYNAPSE (cont.): b. Structural features: i. Membranes of both cells are separated by a space called the synaptic cleft. ii. The axon terminal (presynaptic terminal) contains synaptic vesicles filled with neurotransmitters. iii. Vesicles fuse with the presynaptic membrane to release neurotransmitters into synaptic cleft. iv. The dendritic terminal (postsynaptic terminal) contains ligand-gated channels that bind the neurotransmitter. v. Junctions can be between axon/dendrites, axon/soma, axon/axon, dendrite/dendrite, dendrite/soma. c. Function: communication of electrical information in the form of a chemical signal to from one neuron to another neuron. The chemical signal is converted into an electrical signal in the postsynaptic neuron. 3
  4. 4. NS5 – SYNAPTIC TRANSMISSION IV. NEURONAL SIGNALLING Table 2: Comparison of Graded Potentials and Action Potentials Characteristics Graded Potentials Action Potentials Arise in dendrites and soma Arise at trigger zones Origin Occurs in most membranes (not ex- Propagates along axon citable) Only possible at excitable membranes Chemical (ligand) Voltage Mechanical Types of channels Light Heat Localized (communication over a few Long distance communication Conduction mm) Propagated Not propagated Depends on strength of stimulus All or none Amplitude < 1 mV to > 50mV 100 mV Duration msec – minutes 0.5 - 2 msec Hyperpolarizing (inhibitory to genera- Depolarizing phase  repolarizing tion of action potential) o phase  resting potential Polarity Depolarizing (excitatory to generation of action potential) Refractory Period No Yes Temporal and spatial summation No summation Summation Generator potentials Receptor potentials Types Post-synaptic potentials 4
  5. 5. NS5 – SYNAPTIC TRANSMISSION IV. NEURONAL SIGNALLING A. GENERATOR AND RECEPTOR POTENTIALS 1. Types a. GENERATOR POTENTIALS are caused by energy (heat, light etc) and can elicit an action potential in the sensor neuron. For example, stretch or pressure sensors. b. RECEPTOR POTENTIALS are caused by energy (heat, light etc); they do not elicit an action potential in the sensor neuron. For example, rod and cone cells. 2. Characteristics a. Magnitude of response, that is, change in membrane potential depends on strength of stimulus. b. A sum of multiple (temporal or spatial) graded potentials at the axon hillock is required to generate an action potential. 3. Useful link: http://www.fortunecity.com/greenfield/buzzard/387/gradedpot.htm B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION 1. ACTION POTENTIALS a. Phases: An action potential is divided into several phases. During each phase, different voltage gated channels are activated. Table 3: Phases of an Action Potential Charge on inner State of voltage-gat- State of voltage-gated Range of membrane ed sodium channel potassium channel Phase membrane potential, mV closed - 70 negative closed Resting potential opened after threshold potential reached Na+ flow into cell negative changing - 70 to +30 closed Depolarization to positive cannot respond to sec- ond stimulus (absolute refractory period) inactivated may respond to second open positive changing to stimulus if greater than + 30 to -70 Repolarization negative threshold stimulus K+ ions flow out of cell (relative refractory peri- od) closed closing (relative refractory peri- more negative than od) Na+/ K+ pump returns -70 to -80 Hyperpolarization resting potential membrane potential to resting negative -70 closed closed Resting potential 5
  6. 6. NS5 – SYNAPTIC TRANSMISSION IV. NEURONAL SIGNALLING B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION 1. ACTION POTENTIALS b. Propagation i. Characteristics: self-propagated; away from initiation site (unidirectional) ii. Mechanism: • Local changes in membrane potential result in opening of voltage-gated channels. • Ions flow into cell and diffuse in either direction. Change in membrane potential results in opening of voltage-gated channels in membrane closer to axon terminal; inactivated voltage- gated channels closer to axon hillock will not respond to change in membrane potential, iii. Types • CONTINUOUS: occurs in non-myelinated neurons; slow = 0.2-2 m/sec (velocity) • SALTATORY: occurs in myelinated neurons; fast 12-20 m/sec (velocity) iv. STIMULUS FREQUENCY but NOT stimulus strength INCREASES ACTION POTENTIAL FREQUENCY. c. Summation i. Integration of depolarizing graded potentials allow for the generation of action potentials whereas integration of a depolarizing and a hyperpolarizing potential results in no action potential. ii. Types • Temporal summation occurs when potentials overlap and generate a potential that is overall larger than the individual potentials and allows for depolarization over the threshold which results in an action potential. • Spatial summation is the sum of potentials from different areas of input, usually on the dendrites. Summation of excitatory postynaptic potentials (EPSPs) allows for depolarization over the threshold and will generate an action potential. Summation of inhibitory postsynaptic potentials (IPSPs) will block the generation of action potentials. 2. SYNAPTIC TRANSMISSION a. Characteristics i. Transmission depends on presynaptic release of neurotransmitter and postsynaptic reception of neurotransmitters by receptors. ii. Generates postsynaptic potentials in postsynaptic cell. b. Mechanism: i. Depolarization of membrane near axon terminal causes • activation of voltage-gated sodium channels → influx of Na+ ions • activation of voltage-gated calcium channels → influx of Ca++ ions ii. Influx of Ca++ ions results in vesicle fusion to presynaptic membrane and exocytosis of neurotransmitter. Calcium and sodium ion channels close and ions are pumped out. iii. Neurotransmitter diffuses across synaptic cleft. Rate of diffusion causes synaptic delay. iv. Neurotransmitter binds to receptor on post-synaptic membranes and generates postsynaptic potentials. 6
  7. 7. NS5 – SYNAPTIC TRANSMISSION IV. NEURONAL SIGNALLING B. ACTION POTENTIALS & SYNAPTIC TRANSMISSION 2. SYNAPTIC TRANSMISSION b. Mechanism (cont.) v. Unbound neurotransmitter either degraded or taken up by presynaptic membrane or astrocytes. Bound neurotransmitters are degraded in the postsynaptic cell. c. Synaptic Potentiation: repeated use of a synapse enhances neurotransmitter release. d. Presynaptic Inhibition: regulation of neurotransmitter release by another synapse. e. Neuromodulation of synaptic transmission 3. Links http://www.lifesci.ucsb.edu/~mcdougal/neurobehavior/modules_homework/animation3.html http://www.brainviews.com/abFiles/AniSalt.htm http://outreach.mcb.harvard.edu/animations/synaptic.swf http://www.williams.edu/imput/ (in depth) C. POSTSYNAPTIC POTENTIALS 1. Definition: POST-SYNAPTIC POTENTIALS are graded potentials generated by neurotransmitters bind- ing to receptors on postsynaptic membranes. 2. Mechanism: a. Neurotransmitter binds to receptor. b. Depending on neurotransmitter the outcome is either depolarization (excitatory) or hyperpolarization (inhibitory). c. Membrane permeability is regulated by a variety of channels: chemically (ligand or modulator)-gated channels, voltage-gated channels. 2. Types a. excitatory – will generate an action potential b. inhibitory – reduces the ability to fire an action potential Table 4: Comparison of EPSPs vs. IPSPs membrane potential sodium channels potassium channels chloride channels more positive than depolarization: open, depolarization closed closed resting potential Na+ ion influx repolarization EPSP < -70 mV (e.g. -70 to repolarization (return to open, K+ ion efflux +30 mV) resting potential): closed more negative than closed hyperpolarization: hyperpolarization: resting potential open, K+ ion efflux open, Cl- ion influx depolarization (return IPSP > -70 mV (e.g. -70 to to resting potential): depolarization: depolarization: -120 mV) open closed closed 7
  8. 8. NS5 – SYNAPTIC TRANSMISSION IV. NEURONAL SIGNALLING D. NEUROTRANSMITTERS AND THEIR RECEPTORS 1. Definition: chemical signal synthesized by a presynaptic neuron and released at the axon terminal. 2. Neurotransmitter type (based on chemical structure; function: E = excitatory, I = inhibitory) a. Acetylcholine (E) b. Biogenic amines: dopamine (E/I), serotonin (I), norepinephrine (E/I), histamine c. Amino acids: glutamate (E), aspartate (E), GABA (I), glycine (I) d. Peptides: endorphins(I), enkephalins(I), dynorphins(I), tachykinin(E), somatostatin(I) e. Lipids: anandamide (I, E) f. Gases: NO (E), CO (I) 3. Neurotransmitter receptors a. Definition: postsynaptic membrane proteins that bind presynaptically released chemical signal. b. Types based on function i. Direct action, ionotropic = channel-linked receptors ii. Indirect action, metabotropic = G-protein coupled receptors 8