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Abstract
The hippocampal CA3-CA1 circuit is critical for memory encoding and retrieval. Previous work has shown this feedforward excitatory-inhibitory network (FFEI) maintains a precise excitation-inhibition (E-I) balance onto CA1 pyramidal cells (CA1PCs) (Bhatia et al, 2019). However, how this balance dynamically evolves dependent of the history of sustained input activity is unclear. Deviations from E-I balance are important for gating, normalization, and representation of input ensembles.
Using in vitro whole-cell recordings in mouse hippocampal slices, we probed E-I balance by optogenetically evoking input patterns in CA3 at trains of various frequencies (20-50 Hz) or Poisson stimulus timings (mean 30 Hz). Our results reveal the E-I balance is tightly coupled across frequencies, enabling robust regulation of input gating. However, during stimulus trains, differences in short-term plasticity of excitation versus inhibition temporarily increase excitation relative to inhibition in the initial 2-3 inputs. Preliminary data from inhibition blocking experiments confirm that CA1PCs are most likely to spike within this initial window before inhibition's normalizing force increases.
Voltage clamp recordings also showed this normalizing force of inhibition increases along the stimulus train, causing an inhibition mediated subthreshold divisive normalization. We used this data to train a detailed synaptic model of short-term plasticity within the FFEI network, allowing us to identify the conditions that can potentially lead to escape from E-I balance. This transient deviation may enable enhanced gating, output synchrony, temporal precision, coincidence detection, and ensemble representation within the hippocampal memory circuit. Further studies can look at the interneuron candidates and granularity of this balance.