The Dual Glutamatergic/GABAergic Phenotype of Hippocampal Granule Cells

Abstract

Not only are markers of the glutamatergic and GABAergic phenotype both found in developing hippocampal granule cells but, the activation of these cells simultaneously produces responses mediated by glutamate and GABA receptors in their postsynaptic cells. In the adult, the markers of the GABAergic phenotype and as a consequence, GABAergic transmission disappears. However, these elements can still be transiently expressed in an activity-dependent manner. Indeed, the induction of hyperexcitability in granule cells by LTP-like stimulation in vitro, or by seizures in vivo, up-regulates the GABAergic machinery such that stimulation again provokes monosynaptic GABA receptor mediated responses in their target cells. The putative release of GABA from the mossy fibers (MFs) has been shown to differ according to the postsynaptic cell type in the CA3 area and such release can even activate GABA-A receptors located on the MFs themselves. Accordingly, and despite the emergence of this aberrant GABAergic influx on the CA3 area, the effective inhibitory control on CA3 activity exerted by the dentate gyrus is preserved.

The co-release of glutamate and GABA from single cells gives the central nervous system a powerful computational tool and provides a valuable element to help understand the plasticity inherent in neuronal communication.