Lecture 12: Axonal Propagation and Synaptic Transmission PDF

BPK 306: Principles of Physiological Regulation LECTURE 12 Axonal Propagation and Synaptic Transmission 1  Lecture Objectives Berne & Levy, Ch. 6 1. Explain where on a neuron synaptic input is received and the properti...

BPK 306: Principles of Physiological Regulation LECTURE 12 Axonal Propagation and Synaptic Transmission 1  Lecture Objectives Berne & Levy, Ch. 6 1. Explain where on a neuron synaptic input is received and the properties that determine how much current will flow from dendrite to soma. 2. Compare and contrast EPSPs and IPSPs. Where and how are each produced? 3. Explain what is meant by ‘spatial’ and ‘temporal’ summation and state their physiological consequences. 4. Describe signal transmission at a chemical synapse. 5. Name three classes of neurotransmitter and give an example of an excitatory and an inhibitory neurotransmitter. 6. Using a diagram, explain why axonal conduction is ‘saltatory’, and describe two factors that contribute to the speed of conduction. 7. Explain the difference(s) between ionotropic and metabotropic ion channels and give an example of each. 8. Explain how you could experimentally determine the reversal potential for an EPSP. 2  Synaptic Integration Recording from the cell body of neuron. O Synaptic integration occurs at the axon b large amounts of Nat channels (Nav) hillock, which has the highest density of K&S Fig. 6.8 Nav channels and therefore the lowest threshold for spike initiation. Input is additive both spatially and temporally. mu two subthreshold at similar time 0+ 8 graded pot arrive a , time- > - initiating an Ap by summing together Spatial summation shown in B (also temporal) Temporal summation Whentwograded potfrom > - onepresynaa b c shown in C “Shunting effect” shown in D 3  body EPSPs and IPSPs elKeyIgetoa cell - happens in of > - amplitude depends on strength Stimulus a density of receptor channels if ion flux occurs such that the inside of the strength wh distance travelled is Ap > - Signal loses K&S Fig. 6.3 EPSP (Excitatory postsynaptic potential): Transient depolarization of -70 mV postsynaptic neuron due to increased conductance of the postsynaptic membrane to Na+/K+ in response to neurotransmitter binding -NT to receptor opening kinds , the cham for Not At RMP, driving force for Na+ to enter cell is greater than for K+ to leave, resulting in depolarization. ie) Glutamate if ion flux such that the inside the cell becomes negative un & occurs of IPSP (Inhibitory postsynaptic potential): - -70 mV Transient hyperpolarization of postsynaptic neuron due to (most often) increased Cl- conductance of postsynaptic membrane in response to neurotransmitter binding. >N indp - causeo What is the effect of EPSPs and Cl- enters cell at RMP causing exits or k+ IPSPs on AP generation? hyperpolarization. -make the inside of the difficult to reach neg - more all more threshold voltage to K + Ions (removes fire Ap efflux pos change) 5 · ie) GABA inhibitory NT  Axonal Conduction “The axon doesn’t think: it only ax” Relatively simple function, all or none propogation of AP > - Axons can be unmyelinated or myelinated ↳ fast Nodes of Ranvier are densely populated with NaV channels Produces ‘saltatory’ conduction, in which an AP ‘jumps’ from node to node continuous Ap in unmyelinated vs The larger the axon, the faster the conduction velocity. velocity Conduction is fastest in large, myelinated axons. & Fastestoduction Velocity Properties I : ① larger diameter : decrease axial/internal resistance , less resistance facing the ion flow , more space to travel ② Myelin sheath insulation capacitance separatesthechage ofins a decreases membrane distance the layer atgreater a : redy , , increases membraneesistance the of by ions reducing = number the axon (for ion Kakage along 7  Axonal Conduction Fiber diameter should be m 80-120 35-75 15-30 correct 80-120 35-75 3-15 correct This table is important, but the version in your text has several typos. Please note these changes! K&S Table 5.1 8 Active/Passive Properties of Neurons hyperpolarize decreasing distance over depreciates > Boron & Boulpaep Fig 7-2 9  Regeneration of APs APs are regenerated at nodes of Ranvier for three reasons: 1) membrane conductance is high 2) membrane resistance is low 3) NaV and KV density is high Between nodes, passive potentials propagate rapidly for two reasons 4) Membrane resistance is high 5) Membrane capacitance is low 10  Myelination of Axons Compared to cable with low resistance core and high resistance insulation To improve conduction: – increase diameter of axon (decrease axial resistance) – myelinate the axon (increase membrane resistance) and decreases membranecapacitance – As axon diameter increases, conduction velocity will increase as internal resistance decreases As myelination increases, membrane resistance will increase and capacitance will decrease. Why? And why is this important? ↳ went to get the fastest transmission you to movement when it comes generating 12  Myelination of Axons Larger diameter myelinated axons conduct the fastest. Be able to describe why. "I of transmission speed B&B Ch. 7 K&S Fig 5-10 Reminder: In the CNS: Oligodendrocytes make myelin. In the PNS: Schwann cell make myelin. 14  the Multiple sclerosis (MS): a disease of myelination attacks Oligodendroule its a cas disease sease of demyelination · autoimmune disease degeneration of · cus myelin (oligodendrocytes) · results in impaired conduction ↑ of electrical signals along the axon doesn't convey to next note get toreste loss of myelin - : block > impulse may not 3 conduction - able low density of New Channels > - decreased Rm gone now is /where myelin > - increased In Boron et al. 15  Synaptic Transmission Transmission of electrical signals from one neuron to another at (chemical) synapses NT releas - There are also electrical synapses (e.g. gap junctions), and these seem to have a more important role in the CNS than previously thought (but we won’t discuss them in depth) During synaptic transmission: Input received on dendrites is passively propagated to the hillock EPSP IPSP Input can be excitatory or inhibitory, and summation occurs at hillock If summed signal is subthreshold = no AP If summed signal is suprathreshold = AP occurs and propagates down axon The axon terminus is the presynaptic terminal A dendrite or the cell body of a neighbouring O neuron is the postsynaptic terminal At a synapse, electrical signals are converted to & synapse chemical signals and then back to electrical signals ↳ NT release Kandel et al. Principles of Neuroscience 16  Synaptic Transmission: Electrical Gap Junction Electrical synapses have been known to exist in the CNS for some time, function remains unclear Low-resistance pathway between cells that allows current to flow Electrical synapses are fast and bi-directional, but lack gain Important in the electrical coupling of networks in different CNS regions 17 Synaptic Transmission: Chemical Different types of NTs: CNS Small molecule (glutamate, GABA, acetylcholine) inhibition Gaseous (NO) Amines (dopamine, serotonin, norepinephrine) Some are excitatory (glutamate,) others are inhibitory (GABA, glycine); most have multiple effects This figure is typical of a small molecule NTs. Boron & Boulpaep Fig. 8-2 18 Synaptic Transmission Synaptic transmission by small molecule NTs and neuropeptides is qualitatively similar Transmission involving gaseous NTs differs in several ways – we won’t discuss this in detail. Recall synaptic transmission at the neuromuscular junction and compare it with synaptic transmission. K&S Fig. 6-2 19  Neurotransmitters There are multiple types of NTs (small molecule, peptides, gaseous) and they can be excitatory or inhibitory (or both) Excitatory NTs include: Glutamate (amino acid): Primary excitatory NT in brain Acetylcholine (Ach): In PNS, at NMJ and autonomic ganglia, also CNS in basal ganglia and spinal cord. Ach has two types of receptors: 1. nicotinic (NAChR) at neuromuscular junction 2. muscarinic (MAChR) at autonomic ganglia Inhibitory NTs include: Gamma-aminobutyric acid (GABA): Inhibitory NT in brain Glycine (amino acid): Inhibitory NT in spinal cord Other NTs Dopamine: Motivation, motor function, reward and pleasure Serotonin: Mood, appetite and sleep 20  Postsynaptic NT Receptors Fast Slower EPSPs responses IPSPs CNS: Ionotropic glutamate receptors (NMDA, AMPA) CNS/PNS: Metabotropic glutamate receptors NMJ: Nicotinic ACh receptors (NAChR) PNS: Muscarinic Ach receptors (MAChR) CNS: GABAA, GABAC CNS: GABAB 21 Postsynaptic NT Receptors Cys-loop channels: GABAA,C, glycine, serotonin, ACh Cys-rich loop, pentamers, each subunit has 4TM domains, NT binds N-term, M3 forms pore, permeable to Na+ and K+ Ionotropic glutamate receptors: tetrameric. AMPA (GluR1-GluR1): classic ligand-gated channels NMDA (NR1-NR3): required glu and gly to bind, exhibit voltage-dependent Mg2+ block (requires depolarization to open pore); permeable to Ca2+ BPK306 Fall 2018 22  Summary: Review Questions 1. What properties will determine the conduction of an EPSP through a dendrite? 2. Which ions are most likely to be moving during an IPSP? What about during an EPSP? 3. When two EPSPs occur on the same dendrite in quick succession what can potentially happen and what is this process called? 4. How do membrane resistance and membrane capacitance influence axonal conduction? 5. What are the key difference(s) between ionotropic and metabotropic neurotransmitter receptors? 6. What is meant by the reversal potential of an EPSP? How does this differ from Eion? How could you mesure the reversal potential of an EPSP? 24 Measuring Postsynaptic Potentials Active vs passive Ix = gx(Vm-Ex) Consider an EPSP from a starting Vm of -100 mV compared with one from a holding voltage of -60 No net current, mV? What is likely to happen in at eversal pot. each case? Above: Excitatory post- synaptic currents (EPSCs) - Na+ influx exactly are faster than EPSPs. offsets K+ efflux EPSCs are active (ionotropic channels opening then closing) EPSPs are passive K&S Fig 6-7 30