• Inhibitory synapses release neurotransmitters, typically GABA or glycine, onto other neurons.

• A major difference compared with synapses releasing ACh is the reversal potential of the current through the neurotransmitter receptors.

• Note that the resting potential in these simulations is set to –65 mV, as is characteristic of neurons ,

  • rather than the –90 mV typical of muscle fibers

    • ( The Neuromuscular Junction tutorial )

• Two means of stimulation are available :

  1. through the postsynaptic GABA-gated channels

     • ( AlphaSynapse panel )

  2. through the stimulating electrode inserted in the postsynaptic neuron

     • ( Stimulus Control panel )

• The AlphaSynapse panel controls the parameters of the inhibitory postsynaptic potential

  • onset : time of onset for the IPSP , in ms

  • Tpeak : time to peak of the synaptic conductance change , in ms

  • gmax : postsynaptic conductance change caused by the inhibitory transmitter , in μS

  • e : reversal potential ( Vrev ) of the transmitter-gated channels ( default at –65 mV )

1. Choose tutorial "Postsynaptic Inhibition"

2. Click on Start the Stimulation

3. Reposition Voltage vs. Time plot to the top of your screen

4. Increase Total # ms to 4 ms

5. Change Vrev ( e ) to –66 mV

6. Click on Reset & Run

7. Keep Lines

8. Double postsynaptic conductance to 4 μS , and then to 8 μS

1. Describe the relationship between opening neurotransmitter receptors ( postsynaptic conductance ) and the response of membrane voltage and current.

   • $g_{\text{max}}\propto I$$g_{\text{max}} \propto\ I$

   • $g_{\text{max}}\propto \mathrm{\Delta }{V}_m$$g_{\text{max}}\ \propto\ \Delta V_m$

   • opening more GABA receptors ➡️ more $C{l}^{-}$$Cl^-$ entry and $K^{+}$$K^+$ exit ➡️ $V_m$$V_m$ moves towards reversal potential ( $-66mV$$-66\ mV$ )

9. Click on the Stimulus Control panel and select I-Clamp to inject 5 nA ( +5 ) of depolarizing current into the postsynaptic neuron.

10. Click on run control and change the total #( ms ) to 30.

11. Change onset to 15 ms ( AlphaSynapse panel ). { delays stimulating the inhibitory neuron }

12. Assure that gmax for the inhibitory conductance is 8 μS.

2. Describe the relationship between opening neurotransmitter receptors ( postsynaptic conductance ) and the response of membrane voltage or current.

   • the reversal potential is -65 mV

     • this is NOT the Vm

   • because the reversal potential is negative , its inhibitory

   • so we inject current for 25 milli seconds ,

     • so we depolarize

   

   • if you increase the duration of current injection long enough ,

     • the membrane will eventually reach full charged capacity , $V_{max}=-54mV$$V_{max} = -54\ mV$ at around $21ms$$21\ ms$

   • so for the first 15 seconds it was still charging

   • then some inhibitory channel opens from the alpha synapse , and we hyperpolarize the membrane as it approaches its Nernst at $-66mV$$-66\ mV$

   • the alpha synapse quickly inactivates , and we continue with our current injection until 25 ms

13. Change the current injection to –5 nA.

3. Describe the relationship between opening neurotransmitter receptors ( postsynaptic conductance ) and the response of membrane voltage or current.

   • the opposite happens

   • we charge the membrane with negative current

   • then at 15 ms we open inhibitory channels open ,

     • or either way we now balance going towards its reversal potential at -66 mV

4. Comment on the description of this neurotransmitter.

   • GABA or glycine

   • reversal potential is hyperpolarizing at -66 mV

14. Click on add HH Channels

    • The AlphaSynapse panel automatically adjusts inhibitory neurotransmitter conductance to 0 μS when adding HH channels

15. In the Run Control panel change total #(ms) to 20 ms.

16. In the Stimulus Control panel set the delay at 2 ms , the duration at 2 ms , and the current at 5 nA

    • triggers action potentials by injecting depolarizing current into the neuron

17. Click Reset & Run

14. Increase the injected current to 6 nA , 7 nA , and then 8 nA

5. Describe the response

   • you see an action potential at 6 nA

   • the more current you inject :

     • the quicker an action potential occurs

     • the larger $V_{\text{max}}$$V_{\text{max}}$ is

19. Now adjust ( AlphaSynapse panel ) onset to 2 ms , Tpeak to 2 ms , and gmax to 2 μS.

6. Note the change in these parameters , whether it was an increase or a decrease

   • onset = increase

   • Tpeak = increase

   • gmax = increase ( from 0 to default of 2 )

20. Maintain the reversal potential ( e ) at –66 mV.

21. Repeat the current injections of 5 nA , 6 nA , 7 nA , and 8 nA.

7. Describe how these action potentials compare with the previous set.

   • at 2 ms we inject both positive current and open an inhibitory ion channel ( negative current )

   • these compete for their delivered durations of 2 ms

   • but then the cell continues to hyperpolarize ,

     • the alpha synapse shows we have current until 15 ms

     • so they are still open , hyperpolarizing the membrane potential

     • they eventual close at around 16 ms

8. Describe how the postsynaptic current is altered ( current through the neurotransmitter receptors )

   • the driving force is larger when the membrane depolarizes farther away from reversal potential ( –66 mV )

   • synaptic conductance stays the same

   • current increases through the inhibitory channels

9. Describe the ability of the neuron to generate actions potential during opening of inhibitory neurotransmitter receptors

   • suppressed

   • the opening of inhibitory neurotransmitter receptors prevents the membrane from reaching threshold