Biochemical plasticity of short-axon interneurons: Increased glutamate decarboxylase activity in the denervated area of rat dentate gyrus following entorhinal lesion

Abstract

The entorhinal cortex of adult rats was destroyed unilaterally, thus denervating the outer two-thirds of the molecular layer of the ipsilateral dentate gyrus. The biochemical response of short-axon GABAnergic interneurons intrinsic to the dentate gyrus was subsequently determined by laminar analysis of glutamate decarboxylase, an enzyme associated with boutons of these neurons. Glutamate decarboxylase activity was unaffected by entorhinal lesion for at least 10 days. However, when measured 29–38 days after operation, the absolute and specific activities of glutamate decarboxylase were respectively 45 and 63% greater in the outer part of the molecular layer of the operated side than in the corresponding zone of the control side. The difference between the two sides in specific activity was still significant, though reduced in magnitude, 90 days or more after operation. All statistically significant changes in glutamate decarboxylase activity were confined exclusively to the denervated region. Therefore, inhibitory projections of intrinsic interneurons, like intact excitatory afferents in close proximity to the degeneration, respond to entorhinal lesion in a manner suggesting increased input to the granule cells in compensation for the loss of excitatory entorhinal input. We suggest that additional GABAnergic boutons may be formed by axon sprouting or, alternatively, that an increase in glutamate decarboxylase activity within existing connections may be transsynaptically induced.