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We provided recent experimental evidence that coincident unitary events sum slightly sublinearly when targeting closely located postsynaptic sites. Simultaneous activation of many co-aligned inputs might lead to more significant nonlinear interactions especially in compartments of relatively small diameter. The axon initial segment of pyramidal cells has a limited volume and it receives inputs only from a moderate number of axo-axonic interneurons. We recorded the interaction of unitary axo-axonic inputs targeting a layer 4 pyramidal cell and determined the exact number and position of synapses mediating the effects. Both axo-axonic cells established three synaptic release sites on the axon initial segment of the postsynaptic cell which received a total of 19 synapses. The summation of identified inhibitory postsynaptic potentials (IPSPs) was slightly sublinear (9.4%) and the time course of sublinearity was slower than that of the IPSPs. Repeating the experiment while holding the postsynaptic cell in voltage clamp mode showed linear summation of inhibitory postsynaptic currents (IPSCs), suggesting that a local decrease in driving force could contribute to the sublinear summation measured in voltage recordings. The results indicate that moderate sublinearity during the interaction of neighboring inputs might be preserved in cellular compartments of relatively small volume, even if a considerable portion of all afferents converging to the same domain is simultaneously active.

Summation of Unitary IPSPs Elicited by Identified Axo-axonic Interneurons