title: Dynamic modulation of an orientation preference map by GABA responsible for age-related cognitive performance.
abstract: Accumulating evidence suggests that cognitive declines in old (healthy) animals could arise from depression of intracortical inhibition, for which a decreased ability to produce GABA during senescence might be responsible. By simulating a neural network model of a primary visual cortical (V1) area, we investigated whether and how a lack of GABA affects cognitive performance of the network: detection of the orientation of a visual bar-stimulus. The network was composed of pyramidal (P) cells and GABAergic interneurons such as small (S) and large (L) basket cells. Intrasynaptic GABA-release from presynaptic S or L cells contributed to reducing ongoing-spontaneous (background) neuronal activity in a different manner. Namely, the former exerted feedback (S-to-P) inhibition and reduced the frequency (firing rate) of action potentials evoked in P cells. The latter reduced the number of saliently firing P cells through lateral (L-to-P) inhibition. Non-vesicular GABA-release, presumably from glia and/or neurons, into the extracellular space reduced the both, activating extrasynaptic GABAa receptors and providing P cells with tonic inhibitory currents. By this combinatorial, spatiotemporal inhibitory mechanism, the background activity as noise was significantly reduced, compared to the stimulus-evoked activity as signal, thereby improving signal-to-noise (S/N) ratio. Interestingly, GABA-spillover from the intrasynaptic cleft into the extracellular space was effective for improving orientation selectivity (orientation bias), especially when distractors interfered with detecting the bar-stimulus. These simulation results may provide some insight into how the depression of intracortical inhibition due to a reduction in GABA content in the brain leads to age-related cognitive decline.
authors.affiliation: Department of Psychology, University of Victoria, Victoria, BC, Canada.
authors.forename: Ai
authors.initials: A
authors.lastname: Miyamoto
authors.forename: Jun
authors.initials: J
authors.lastname: Hasegawa
authors.forename: Osamu
authors.initials: O
authors.lastname: Hoshino
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000502:physiology*; D000818:Animals; D003071:Cognition / Q000502:physiology*; D003198:Computer Simulation; D008959:Models, Neurological; D009415:Nerve Net / Q000502:physiology*; D009433:Neural Inhibition / Q000502:physiology; D016571:Neural Networks, Computer; D009474:Neurons / Q000502:physiology; D014793:Visual Cortex / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
chemical_list: D005680:gamma-Aminobutyric Acid