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Cereb Cortex. 2020 Feb 20. pii: bhz334. doi: 10.1093/cercor/bhz334. [Epub ahead of print]

Synaptic Mechanisms Underlying the Network State-Dependent Recruitment of VIP-Expressing Interneurons in the CA1 Hippocampus.

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Department of Biochemistry, Microbiology and Bio-informatics, Laval University, Québec, PQ, Canada.
Neuroscience Axis, CHU de Québec Research Center (CHUL), Québec, PQ, Canada.
Krembil Research Institute, University Health Network, Toronto, ON, Canada.
Department of Physiology, University of Toronto, Toronto, ON, Canada.
Institut de Biologie de l'ÉcoleNormale Supérieure (IBENS), École Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France.
New York University Neuroscience Institute, New York, NY, USA.
Departments of Medicine (Neurology) and Physiology, University of Toronto, Toronto, ON, Canada.


Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells is provided by the interneuron-specific interneurons that express the vasoactive intestinal polypeptide (VIP-IS) and innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined the impact of synaptic inputs onto the network state-dependent recruitment of VIP-IS cells. We found that VIP-IS cells fire spikes in response to both the Schaffer collateral and the temporoammonic pathway activation. Moreover, by integrating their intrinsic and synaptic properties into computational models, we predicted recruitment of these cells between the rising phase and peak of theta oscillation and during ripples. Two-photon Ca2+-imaging in awake mice supported in part the theoretical predictions, revealing a significant speed modulation of VIP-IS cells and their preferential albeit delayed recruitment during theta-run epochs, with estimated firing at the rising phase and peak of the theta cycle. However, it also uncovered that VIP-IS cells are not activated during ripples. Thus, given the preferential theta-modulated firing of VIP-IS cells in awake hippocampus, we postulate that these cells may be important for information gating during spatial navigation and memory encoding.


calretinin; disinhibition; network oscillations; ripples; theta


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