title: Molecular aspects of age-related cognitive decline: the role of GABA signaling.
abstract: Alterations in inhibitory interneurons contribute to cognitive deficits associated with several psychiatric and neurological diseases. Phasic and tonic inhibition imparted by γ-aminobutyric acid (GABA) receptors regulates neural activity and helps to establish the appropriate network dynamics in cortical circuits that support normal cognition. This review highlights basic science demonstrating that inhibitory signaling is altered in aging, and discusses the impact of age-related shifts in inhibition on different forms of memory function, including hippocampus-dependent spatial reference memory and prefrontal cortex (PFC)-dependent working memory. The clinical appropriateness and tractability of select therapeutic candidates for cognitive aging that target receptors mediating inhibition are also discussed.
authors.affiliation: Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: McQuail
authors.affiliation: Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA.
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Frazier
authors.affiliation: Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA. Electronic address: bizonj@ufl.edu.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Bizon
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000502:physiology*; D003071:Cognition / Q000502:physiology*; D006801:Humans; D017397:Prefrontal Cortex / Q000378:metabolism; D018079:Receptors, GABA / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D018079:Receptors, GABA; D005680:gamma-Aminobutyric Acid
keywords: GABA(A) α5; GABA(B) receptor; hippocampus; memory; prefrontal cortex; tonic inhibition