title: Disinhibition, an emerging pharmacology of learning and memory.
abstract: Learning and memory are dependent on interactive excitatory and inhibitory mechanisms. In this review, we discuss a mechanism called disinhibition, which is the release of an inhibitory constraint that effectively results in an increased activity in the target neurons (for example, principal or projection neurons). We focus on discussing the role of disinhibition in learning and memory at a basic level and in disease models with cognitive deficits and highlight a strategy to reverse cognitive deficits caused by excess inhibition, through disinhibition of α5-containing GABAAreceptors mediating tonic inhibition in the hippocampus, based on subtype-selective negative allosteric modulators as a novel class of drugs.
authors.affiliation: Institute of Pharmacology, University of Zurich, Zurich, Switzerland; Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology Zurich, Zurich, Switzerland.
authors.forename: Hanns
authors.initials: H
authors.lastname: Möhler
authors.affiliation: Laboratory of Genetic Neuropharmacology, McLean Hospital, Belmont, MA, USA; Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
authors.forename: Uwe
authors.initials: U
authors.lastname: Rudolph
keywords: GABAA; Pavlovian learning; allosteric modulators; disinhibition; somatostatin