Local structural balance and functional interaction of excitatory and inhibitory synapses in hippocampal dendrites

Theoretical and experimental studies on the computation of neural networks suggest that neural computation results from a dynamic interplay of excitatory and inhibitory (E/I) synaptic inputs. Precisely how E/I synapses are organized structurally and functionally to facilitate meaningful interaction remains elusive. Here we show that E/I synapses are regulated across dendritic trees to maintain a constant ratio of inputs in cultured rat hippocampal neurons. This structural arrangement is accompanied by an E/I functional balance maintained by a 'push-pull' feedback regulatory mechanism that is capable of adjusting E/I efficacies in a coordinated fashion. We also found that during activity, inhibitory synapses can determine the impact of adjacent excitatory synapses only if they are colocalized on the same dendritic branch and are activated simultaneously. These fundamental relationships among E/I synapses provide organizational principles relevant to deciphering the structural and functional basis for neural computation within dendritic branches.