Intrinsic GABA neurons inhibit proenkephalin gene expression in slice cultures of rat neostriatum

In the neostriatum, the proenkephalin gene is expressed in medium spiny GABA neurons, which project to the globus pallidus. The expression is activated by glutamatergic projections from the neocortex via NMDA receptors. In these experiments we have used slice cultures of rat neostriatum to study the role of GABA in proenkephalin gene expression. Our results show that GABA is released from neostriatal neurons and negatively regulates the proenkephalin gene expression induced by NMDA receptor stimulation. The GABAA receptors involved seem to be colocalized with NMDA receptors on the projection neurons, which express the proenkephalin gene. In further experiments, we have found that the proenkephalin gene expression is not only activated by neocortical projection neurons but also by intrinsic striatal neurons as well as by projections from the thalamus. All these glutamatergic afferents enhance the proenkephalin gene expression via NMDA receptors. Their efficacy is regulated by endogenous GABA.