Interneurons of the dentate gyrus: an overview of cell types, terminal fields and neurochemical identity

Interneurons of the dentate gyrus are a diverse group of neurons that use GABA as their primary neurotransmitter. Morphological studies of these neurons have been challenging since no single neuro-anatomical method provides a complete view of these interneurons. However, through the integration of findings obtained from multiple methods, an interesting picture of this complex group of neurons is emerging, and this review focuses on studies in rats and mice. In situ hybridization of mRNAs for the two isoforms of the GABA synthesizing enzyme, glutamate decarboxylase (GAD65 and GAD67), demonstrates the abundance of GABA neurons in the dentate gyrus and their high concentration in the hilus and along the base of the granule cell layer. Likewise, immunohistochemical studies, particularly of GAD65, demonstrate the rich fields of GABA terminals not only around the somata of granule cells but also in the dendritic regions of the molecular layer. This broad group of GABA neurons and their terminals can be subdivided according to their morphological characteristics, including the distribution of their axonal plexus, and their neurochemical identity. Intracellular labeling of single interneurons has been instrumental in demonstrating the extensiveness of their axonal plexus and the relatively specific spatial distribution of their axonal fields. These findings have led to the broad classification of interneurons into those that terminate primarily at perisomatic regions and those that innervate the dendrites of granule cells. The interneurons also can be classified according to their neuropeptide and calcium-binding protein content. These and other molecules contribute to the rich diversity of dentate interneurons and may provide opportunities for selectively regulating specific groups of GABA neurons in the dentate gyrus in order to enhance their function or protect vulnerable neurons from damage.