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Abstract
Feedforward inhibition (FFI) enables pyramidal cells in area CA1 of the hippocampus (CA1PCs) to remain easily excitable while faithfully representing a broad range of excitatory inputs without quickly saturating. Despite the cortical ubiquity of FFI, its specific function is not completely understood. FFI in CA1PCs is mediated by two physiologically and morphologically distinct GABAergic interneurons: fast-spiking, perisomatic-targeting basket cells and regular-spiking, dendritic-targeting bistratified cells. These two FFI pathways might create layer-specific computational sub-domains within the same CA1PC, but teasing apart their specific contributions remains experimentally challenging. We implemented a biophysically realistic model of CA1PCs using 40 digitally reconstructed morphologies and constraining synaptic numbers, locations, amplitude, and kinetics with available experimental data. First, we validated the model by reproducing the known combined basket and bistratified FFI of CA1PCs at the population level. We then analyzed how the two interneuron types independently affected the CA1PC spike probability and timing as a function of inhibitory strength. Separate FFI by basket and bistratified respectively modulated CA1PC threshold and gain. Concomitant FFI by both interneuron types synergistically extended the dynamic range of CA1PCs by buffering their spiking response to excitatory stimulation. These results suggest testable hypotheses on the precise effects of GABAergic diversity on cortical computation.
Highlights
CA1 Pyramidal Cells (CA1PCs) constitute the output of the hippocampal tri-synaptic circuit, relaying the information processed by area CA3 onto the subiculum and the deep layers of the entorhinal cortex
The present study investigates the specific effects of basket and bistratified feedforward inhibition (FFI) on CA1PC using biophysically and morphologically detailed computational simulations constrained by and validated against experimental data
What are the distinct contributions of basket and bistratified cells to the CA1PC dynamic range extension? When only activating bistratified synapses while selectively blocking basket synapses in the simulation, FFI mostly affects the recruitment of Correspondingly, CA1PCs requiring more than 30 synapses to be recruited are considered ‘‘less excitable’’
Summary
CA1 Pyramidal Cells (CA1PCs) constitute the output of the hippocampal tri-synaptic circuit, relaying the information processed by area CA3 onto the subiculum and the deep layers of the entorhinal cortex. CA1PCs activity encodes spatial (O’Keefe and Dostrovsky, 1971) and temporal (MacDonald et al, 2011) features of episodic memories. This representation is mediated by the integration of excitatory and inhibitory inputs from ∼30,000 glutamatergic and ∼1700 GABAergic synapses, respectively (Megías et al, 2001). FFI allows CA1PC dendrites to sum incoming activity over broader time windows while enforcing precise coincidence detection in the soma (Pouille and Scanziani, 2001). This mechanism increases the temporal fidelity of the circuit by reducing spike onset jitter
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