Activity-Dependent Regulation of Inhibition in Visual Cortical Cultures

Abstract

Maintaining the correct balance of inhibition and excitation is extremely important for normal cortical function. Too little inhibition can lead to epileptiform activity, whereas too much inhibition can severely depress cortical responsiveness. This suggests that the balance of inhibition and excitation in cortical circuits should be tightly regulated. In visual cortex, activity has been shown to affect expression of the inhibitory neurotransmitter GABA in a manner consistent with a role in balancing excitation and inhibition; blocking activity in one eye leads to a down-regulation of GABA in the corresponding ocular dominance columns (Hendry and Jones, 1986). These data suggest that the level of activity is acting through some feedback signal to locally adjust the strength of cortical inhibition, although the mechanism by which this occurs remains unclear. Here we use a culture system to explore the role of activity in the control of cortical inhibition. We have found that blocking activity in culture leads to a reversible decrease in the number of neurons immunopositive for GABA, and that this decrease can be prevented by the coapplication of brain-derived neurotrophic factor (BDNF). These data suggest that activity levels can continuously adjust cortical inhibition in a bi-directional manner through a BDNF-dependent mechanism.