Changes in inhibitory mechanisms in human visual cortex throughout the lifespan

Abstract

Inhibitory processes play a key role in shaping visual perception and many studies have suggested that changes in visual perception throughout the lifespan are linked with changes in neural inhibitory mechanisms. GABA is the major inhibitory neurotransmitter in visual cortex and GABAergic mechanisms are involved in developmental plasticity influencing the maturation of receptive field properties, the spatial and temporal integration of signals, and the timing of neural circuits. The synchronized firing of target neurons is a key function of the GABAergic inhibitory system and the presynaptic cannabinoid receptor — CB1 — can inhibit GABA release, depressing fast synaptic signaling and disrupting temporally coordinated firing among neurons. We have studied CB1 expression in human visual cortex throughout the lifespan using Western blot analysis of postmortem tissue samples. We determined the developmental profile of CB1 expression and compared it with the maturation of the GABAASPLTRAK(1)2 receptor subunit which is found at the same inhibitory synapses. CB1 expression is initially very high in infant visual cortex ([[lt]] 1 year of age), falls to low levels between 1–4 years of age, rises steadily to reach the highest levels during the teenage years, then falls again into adulthood showing a small roll off with aging. GABAASPLTRAK(1)2 receptor subunit expression is also very high in infants ([[lt]] 1 year) and then falls to about half that level where it remains. We compared the CB1:GABAASPLTRAK(1)2 ratio and found that initially there is more GABAASPLTRAK(1)2, then between 4–20 years of age there is a switch to substantially more CB1, followed by balanced expression in young adults and slightly less CB1 in older adults. Taken together, these changes in CB1and GABAASPLTRAK(1)2 expression in human visual cortex suggest that there may be substantial developmental variations in fast synaptic signaling that affect synchronized firing among populations of neurons as well as visual perceptions that depend on temporally coordinated neural activity.