Distinct and synergistic feedforward inhibition of pyramidal cells by basket and bistratified interneurons

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dc.contributor.authorFerrante, Michele
dc.contributor.authorAscoli, Giorgio A.
dc.date.accessioned2016-07-27T17:27:21Z
dc.date.available2016-07-27T17:27:21Z
dc.date.issued2015-11-05
dc.description.abstractFeedforward 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.
dc.description.sponsorshipThis work was supported in part by National Institutes of Health grant R01 NS39600, Office of Naval Research grant MURI N00014-10-1-0198, and National Science Foundation grant RI IIS-1302256 to GAA. Publication of this article was funded in part by the George Mason University Libraries Open Access Publishing Fund.
dc.identifier.citationFerrante M and Ascoli GA (2015) Distinct and synergistic feedforward inhibition of pyramidal cells by basket and bistratified interneurons. Front. Cell. Neurosci. 9:439. doi: 10.3389/fncel.2015.00439
dc.identifier.doihttp://dx.doi.org/10.3389/fncel.2015.00439
dc.identifier.urihttps://hdl.handle.net/1920/10309
dc.language.isoen_US
dc.publisherFrontiers
dc.subjectFeedforward inhibiton
dc.subjectBistratified
dc.subjectBasket
dc.subjectInterneurons
dc.subjectCA1 pyramidal cells
dc.subjectNeuronal connectivity
dc.subjectHippocampus
dc.subjectInput-output transformation
dc.titleDistinct and synergistic feedforward inhibition of pyramidal cells by basket and bistratified interneurons
dc.typeArticle

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