Dynamic modulation of an orientation preference map by GABA responsible for age-related cognitive performance.

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.