Cholinergic modulation of dentate gyrus processing through dynamic reconfiguration of inhibitory circuits

The dentate gyrus (DG) of the hippocampus plays a key role in memory formation, and it is known to be modulated by septal projections. By performing electrophysiology and optogenetics, we evaluated the role of cholinergic modulation in the processing of afferent inputs in the DG. We show that mature...

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Bibliographic Details
Authors: Ogando, Mora, Pedroncini, Olivia, Federman, Maria Noel, Romano, Sebastián Alejo, Brum, Luciano Ariel, Lanuza, Guillermo Marcos, Refojo, Damian, Marin Burgin, Antonia
Format: article
Status:Published version
Publication Date:2021
Country:Argentina
Institution:Consejo Nacional de Investigaciones Científicas y Técnicas
Repository:CONICET Digital (CONICET)
Language:English
OAI Identifier:oai:ri.conicet.gov.ar:11336/183953
Online Access:http://hdl.handle.net/11336/183953
Access Level:Open access
Keyword:ACETYLCHOLINE
DENTATE GYRUS
GRANULE CELLS
NEUROMODULATION
PLASTICITY
PV INTERNEURONS
SOM INTERNEURONS
https://purl.org/becyt/ford/1.6
https://purl.org/becyt/ford/1
Description
Summary:The dentate gyrus (DG) of the hippocampus plays a key role in memory formation, and it is known to be modulated by septal projections. By performing electrophysiology and optogenetics, we evaluated the role of cholinergic modulation in the processing of afferent inputs in the DG. We show that mature granule cells (GCs), but not adult-born immature neurons, have increased responses to afferent perforant path stimuli upon cholinergic modulation. This is due to a highly precise reconfiguration of inhibitory circuits, differentially affecting Parvalbumin and Somatostatin interneurons, resulting in a nicotinic-dependent perisomatic disinhibition of GCs. This circuit reorganization provides a mechanism by which mature GCs could escape the strong inhibition they receive, creating a window of opportunity for plasticity. Indeed, coincident activation of perforant path inputs with optogenetic release of acetylcholine produces a long-term potentiated response in GCs, essential for memory formation.