Upinder S. Bhalla | Excitatory-inhibitory balance and timing in the hippocampus explored using combinatorial optical stimulation

Abstract

Many neural circuits are believed to be in close excitatory-inhibitory (E-I) balance. This makes it possible for neurons to receive a broad latent pool of inputs, but 'pay attention' only to a few whose excitation overrides inhibition. Thus E-I balance has important implications for excitability, input gating, and neuronal summation. While global balance is well-established, it is unclear how closely E and I balance out at the level of few synapses, and how precisely the timings of the E and I inputs match up. We used optogenetic stimuli in CA3, delivered in a grid pattern, to sample a very wide stimulus space with tight control over timing, subsets, and number of cells. We monitored responses in CA1, with and without inhibitory blockers, to determine the nature and mechanism of balance. We find that E and I are balanced down to a few synapses, and with a timing profile that leads to a distinct form of summation we call subthreshold divisive normalization. This has interesting implications for gating of input subsets and gating in time.