Neurophysiology I Lecture Notes

Neurophysiology I: Nerve Cell Function/Synaptic Transmission ANSC 3080 G. Bedecarrats Learning Objectives Define the structure and function of different classes of neurons Explain the mechanisms in forming membrane potentials Describe the events...

Neurophysiology I: Nerve Cell Function/Synaptic Transmission ANSC 3080 G. Bedecarrats Learning Objectives Define the structure and function of different classes of neurons Explain the mechanisms in forming membrane potentials Describe the events and properties of action potentials Describe and explain synaptic transmission Nervous System Organization Afferent Efferent Efferent 1  Nervous System Composition Nervous tissue is composed of two types of cells:  Neurons:  They are “the” nerve cells able to transmit information  Composed of a cell body and processes (axons and dendrites) Axon = info moves away from cell body Dendrite = info moves towards cell body Cell body = integrates in- and outgoing information Neurons can be categorized based on the number of processes: Multipolar, mainly in CNS (top) Pseudounipolar, mainly in PNS (middle) Bipolar, mainly sensory organs (bottom)  Neurons also classified by function  Sensory (afferent): from PNS to CNS  Motor (efferent): from CNS to muscles and glands  Interneurons (association): relay info between neurons within the CNS  Specialized “receptors”: transducers = convert stimuli to signal Glial cells: non-neuronal cells; 10X more abundant than neurons (oligodendrocytes, astrocytes, ependymal cells, microglia) Provide structural support to nervous tissue Participate in myelin formation (oligodendrocytes) Secrete glutamate: can modulate excitatory level of neurons (astrocytes) Some possess phagocytic activity (microglia) Contact both blood vessels and neurons = transport of nutrients  neurons do not store glucose or Oxygen 2 Glial cells from a rabbit brain observed using a confocal microscope developed by Molecular Dynamics, Inc. White / Grey Matter  Grey matter corresponds to cell bodies  White matter corresponds to bundles of neuron processes with the white appearance due to myelin sheaths  Nerves = bundles of axons; run from or to the CNS  Cell bodies of sensory neurons are located in clusters named ganglia (outside of the CNS)  Cell bodies of motor nerves are located in well-defined area of the CNS (brain and spinal cord) Myelin Sheaths (oligodendritic in CNS, Schwann cells in PNS)  Myelin = white lipid (sphingomyelin) around nerve fibers  Glial cells wrapped around an axon  Looses its cytoplasm = layers of lipids  Only in white matter (not all fibers)  Electrical insulator  Interruptions = nodes of Ranvier (every 1-2 mm). Denuded axon points will allow depolarisation = transmission of action potential (AP)  Transmission of AP faster in myelinated fibers 3  Membrane Potential  Every cell of the body possesses a membrane potential = Resting Membrane Potential (RMP)  RMP results from a difference in charge across the cell membrane (between cytosol and extracellular fluid)  Inside of membrane negative RELATIVE to outside  Absolute value differs between cell type and depends on the amount of charges, ion channels and the thickness of the membrane  Average RMP in a nerve cells around –70 to –90 mV Intra- and extracellular compartments are electroneutral In the cytosol, negative charges carried by large organic molecules are attracted to the membrane by positive charges on the outside. What maintains the RMP? Combination of: 1. Selective permeability (passive based on diffusion). 2. Na+/K+ pump (3 Na+ out 2 K+ in) 3. Large anions trapped on the inner surface of membrane 4  Maintenance of the RMP Selective permeability (diffusion):  Passive leakage of ions through channels (concentration gradient)  Resting membrane permeable to K+, barely permeable to Na+, Ca2+ and Cl-  positive charges accumulate outside Ion pumps:  Concentration of ions remains relatively constant inside the cell  needs to compensate for diffusion leakage  Na+/K+ pump: pumps 3 Na+ out and brings 2 K+ in  Goes against concentration gradients and for Na+, against the membrane polarity (outside already positive relative to inside)  Requires a lot of energy up to 40% of ATP availability Note: neurons do not store glucose or O2  constant supply needed Excitable Cells  Cells that can generate electrical impulses (Action Potentials)  They need to be stimulated  Chemical, electrical or physical stimulations induce a change in membrane potential to reach a THRESHOLD provoking the opening of voltage gated ion channels  If Na+ channels open (or Ca2+ in certain nerve endings and smooth and cardiac muscle cells), Na+ rushes inside the cell (gradient concentration)  potential less negative, then inverted (positive) = DEPOLARIZATION  Subsequent opening of K +channels results in an outflow of K+ returning the potential to RMP = REPOLARIZATION 5  Generation of Action Potentials in Neurons  First, an initial depolarization (stimulation) needs to reach threshold to provoke the opening of Na+ voltage gated channels = Depolarization  After about 0.5 ms, opened Na+ channels close rapidly  K+ voltage gated channels then open (delayed compared to Na+ channels)  outflow of K+ = Repolarization  K+ voltage gated channels then progressively close, outflow of K+ continues after reaching the RMP = Hyperpolariztion  Once all gated channels are closed, ions rejoin their respective compartments by diffusion and Na+/K+ pumps  Neurons cannot be re-stimulated until RMP is restored = REFRACTORY PERIOD 6  FYI: Typical voltage gated Na+ channel Two gates: activation and inactivation gates Activation gate is electrically charged a) Resting: activation gate closed, inactivation gate opened b) Depolarization: activation gate opens, inactivation gate remains opened c) After short delay: closing of the inactivation gate d) Repolarization: Activation gate closes but the inactivation takes more time to reopen (new depolarization not possible = refractory period) Ion Gated Channels  Several types of gated channels:  Voltage-gated channels  Ligand-gated channels: binding sites for neurotransmitters  Each channel is composed of several subunits, and has various degrees of specificity All-or-none Rule  Nerve cells follow the all- or-none rule  When threshold is met an AP is generated  The amplitude of the AP is fixed for that cell  Intensity encoded by the frequency of Aps, not the amplitude 7  Conduction of Action Potential  Depolarization and repolarization processes (AP) propagate along the cell membrane  Need for the change in potential to reach threshold on the nearby microdomain to trigger opening of gated channels In unmyelinated axons: In myelinated axons:  AP occurs the same way but only at the nodes of Ranvier  Myelin prevents ion leakage, current jumps from one node to the other = SALTATORY conduction  Velocity increased as less membrane affected = less energy required to transport ions  Nerve velocity depends on dissipation of current  Thickness of myelin  Diameter of the fiber (thicker = faster)  Range from 100 to 0.5 m/sec and from 2500 to 250 impulses/sec Synaptic Transmission  Continuity of signal between a neuron and other neurons or between a neuron and target cells such as skeletal muscles (neuromuscular synapse)  Cell membrane made of phospholipids = electric insulator  A gap exists between pre- and post-synaptic cell membranes = synaptic gap or cleft Rarely, direct continuity in electric impulse = gap junction (cardiac and some smooth muscles) In vertebrates, neuronal synapses = predominantly CHEMICAL synapses 8  Neurotransmitters  Molecules able to transmit information from a neuron: convert the electrical signal (AP) into a chemical signal  Released by pre-synaptic neuron into the gap  Bind to specific receptors on post-synaptic membrane  Elicit a response  Classified based on their molecular size and composition Small molecules:  Synthesized in the nerve terminals by specific enzymes  Amino Acid derivatives; Biogenic amines Neuropeptides (3-40 AA):  Synthesized in the cell body  Packaged in secretory vesicles  Transported to the site of release FYI 9  General Mechanism of Action (case of the neuromuscular synapse)  Postsynaptic folding is common in neuromuscular synapse (not in interneurons) = increases surface  Acetylcholine (ACh) = neuromuscular synapse transmitter 1. Action potential (AP) 2. AP opens voltage gated Ca2+ channels = in-flux of Ca2+ 3. Ca2+ triggers exocytosis 4. Diffusion in the cleft 5. Binding to specific receptors 6. Ion channels open on post-synaptic membrane = depolarization 7. Neurotransmitter inactivated termination of signal FYI Quinn, M. Chapter 8 Muscle Physiology. Slide 28 http://slideplayer.com/slide/4428030/ 10  Termination of Transmission For small molecules: Picked back up by presynaptic neuron via endocytosis and recycled for next time Deactivated in the cleft by enzymes released by post- synaptic cell (ie Acetycholine Esterase) For neuropeptides: After binding to its receptor, can be internalized by post-synaptic cell via endocytosis and be degraded by cellular enzymes Broken down by extracellular peptidase in the gap Receptor can be desensitized Integration of Multiple Synapses Between Neurons  In the case of neuro-muscular synapse, 1 neuron = AP = muscle cell depolarization  In neuron-neuron synapse:  1 neuron can receive impulse from multiple other neurons  Synapses can be either excitatory or inhibitory  1 impulse does not always lead to a response (need to reach threshold)  Excitatory synapse = depolarization = entry of Na+  Inhibitory synapse = hyperpolarization = entry of Cl- and/or outflow of K+ A & B = excitatory; C = inhibitory a) Excitatory postsynaptic potential (EPS) not sufficient to reach threshold; needs 3 impulses b) Needs impulse from A and B for EPS to reach threshold c) C able to decrease EPS and block excitatory action of A+B 11