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Week 10: Synaptic transmission – Part 1

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1 Week 10: Synaptic transmission – Part 1
BIOL3833 Week 10: Synaptic transmission – Part 1 It took us 8 weeks to understand how a single neuron works. We learned principles that apply broadly throughout the nervous system Now we move on: How do systems and networks of neurons work?

2 What’s Next? Understanding the functional properties of Neural Systems
Examining the nature of communication between two neurons Understanding the behavior of neural networks (Not as easy as many once believed)

3 These inputs occur at the synapse

4 Human brain has about 85 Billion neurons
Each cell sends outputs to 100s of other cells Most cells receive inputs from other cells. So, there are approximately 75 trillion connections in the human brain

5 Understanding the behavior of neural networks
(Not as easy as many once believed)

6 The idea of the Connectome

7 The STG network (connectome):
26-30 Neurons (depending on species) Connections are known Inputs are known AB anterior burster PD pyloric dilator LPG lateral posterior gastric LP lateral pyloric IC inferior cardiac LG lateral gastric MG medial gastric GM gastric mill PY pyloric constrictor VD ventricular dilator Int1 interneuron 1 AM anterior median DG dorsal gastric Stein (2009) J. Comp. Physiol. A

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9 Communication between neurons
The point of communication is the synapse Initial theory (1890s) was that all communication was electrical transmission 1920s - evidence for chemical transmission emerged By 1950s – acceptance of both types of synapse in the nervous system

10 Easiest way to transmit signal from one cell to another?
Let ions move directly between cells

11 “Gap Junction” or “Electrical” synapses
Advantages Fast transmission Disadvantages Loss of signal strength Cannot change polarity Restricted to voltage changes only Useful for Synchronizing activity between neurons Responses that require high speed: For example, escape

12 A more flexible way to transmit signal from one cell to another?
Chemical transmission

13 Presynaptic Events Action potential invades axon terminal Activates voltage gated calcium channels Calcium influx increases probability of vesicle release Vesicles are transferred to the plasma membrane at active zones Vesicle fuses with membrane, releasing neurotransmitter Neurotransmitter diffuses across the synaptic cleft Transmitter binds to postsynaptic cell (more later) Transmitter action is terminated by reuptake or enzymatic degradation

14 Postsynaptic events Transmitter binds to receptor The receptor Directly opens ion channel (ionotropic) or Activates 2nd messenger pathway (metabotropic) The effects of any neurotransmitter are determined by the properties of the receptor, not the transmitter

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16 Chemical synapses Advantages Disadvantages Useful for
Can amplify signals Can transform signals (e.g., change polarity, duration) Wide range of effects on postsynaptic cell (excite, inhibit, change metabolism, alter the function of existing ion channels, etc.) Prolong the effects of the signal Disadvantages Slower than gap junctions Useful for All kinds of stuff

17 Glutamate receptors are excitatory
Most prevalent excitatory receptors in the CNS Three general classes: AMPA, NMDA, and Kainate Numerous variations within each class AMPA receptors: Fast, transient currents, permeable to sodium and potassium NMDA receptors Slow persistent currents, permeable to sodium, potassium and calcium Require Glycine as co-transmitter Magnesium block must be removed for activation

18 Glutamate receptor currents

19 What happens when receptors are permeable to more than one ion?

20 Return of the GHK Equation
The concept of reversal potential Activating a particular type of receptor will move the membrane toward Ereceptor So: activating a population of AMPA receptors will pull the membrane potential toward EAMPA And - Just like with ion channels: IAMPA = (VM – EAMPA)*gAMPA What determines whether a receptor is inhibitory or excitatory is its reversal potential If EREV is above threshold it is excitatory. If EREV is below threshold it is inhibitory.

21 GABA receptors are inhibitory (usually)
GABAA GABAB Why is GABA-A Usually inhibitory? When might it be excitatory? When ECl is above threshold Ionotropic Fast Chloride permeable Usually inhibitory 2nd Messenger targets ion channels Slow Opens nearby K+ channels Always inhibitory

22 GABA-A GABA-B

23 Discuss, debate, conclude (10 minutes): How can a receptor that opens chloride channels be excitatory?

24 Discuss, debate, conclude (10 minutes): If activating a receptor depolarizes the membrane does this guarantee that the receptor is excitatory? The answer is NO:

25 Synaptic simulations: Experimental arrangement
The answer is NO:

26 Your next STEP point: Each table prepares and signs a “Contract for Exam2”
The answer is NO:


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