Figure 3: Diversity of perisomatic-targeting GABA neuron-mediated inhibition in cortical circuits may be due to differences in the reversal potential for the GABAA-mediated current. (a) The scheme illustrates targeting by basket cells (either parvalbumin- or cholechystokinin-positive), which contact the soma and the proximal/perisomatic dendritic compartments, and by chandelier or axoaxonic neurons, which contact the axon initial segment. (b) The schemes illustrate differences in the postsynaptic effect of a GABAAR conductance according to the value of the reversal potential for the GABAA current ( 𝐸 G A B A A ) relative to the resting membrane potential ( 𝑉 m r ) and the threshold potential to fire spikes ( 𝑉 t h ). In (B1) to (B3), the time course of the GABAAR-mediated conductance, chosen to be identical in all panels, is shown by the black traces and the IPSPs are shown by the blue/red traces. Note that the IPSP time course is always slower than the GABAA conductance, although in the scheme the difference in time course is somewhat exaggerated for illustration purposes and does not match the actual time scales. (B1) Illustration of cases in which 𝐸 G A B A A is negative relative to 𝑉 m r ( 𝑉 t h > 𝑉 m r > 𝐸 G A B A A ) , and the GABAA conductance generates a hyperpolarizing IPSP (all blue IPSP trace). As the IPSP outlasts the GABAA conductance, the duration of the inhibitory effect of the synaptic input (shown by the shaded blue rectangle) is extended by the membrane hyperpolarization that remains after the GABAA conductance decays. (B2) Illustration of cases in which the IPSP is depolarizing because 𝐸 G A B A A is positive relative to 𝑉 m r ( 𝑉 t h > 𝐸 G A B A A > 𝑉 m r ) . Just as the hyperpolarizing IPSP, the depolarizing IPSP outlasts the GABAA conductance; however, in this case 𝐸 G A B A A is below 𝑉 t h , and therefore the depolarizing IPSP could have a dual inhibitory/excitatory effect (blue/red IPSP trace), initially producing shunting inhibition which lasts approximately the same time as the GABAA conductance (shaded blue/red rectangle), followed by an enhanced excitability of the postsynaptic neuron due to the remaining phase of the depolarizing IPSP. (B3) Illustration of cases in which 𝐸 G A B A A is positive relative to 𝑉 t h ( 𝐸 G A B A A > 𝑉 t h > 𝑉 m r ) . In this case, the depolarizing IPSP has a purely excitatory effect (shaded red rectangle). Basket cells are thought to produce hyperpolarizing GABAAR-mediated inhibition of pyramidal cells such as that illustrated in (B1). In contrast, the effect of chandelier neuron inputs is currently debatable, some studies suggesting an excitatory as that in (B3), other studies suggesting a purely inhibitory effect. Here, we suggest that depolarizing chandelier cell inputs may have a dual inhibitory/excitatory effect, illustrated in (B2), which could synchronize postsynaptic cells as described in Figure 2, although the depolarizing nature of the IPSP may accelerate the timing of synchronous firing after the postsynaptic cells escape from inhibition.