A Novel Type of GABAergic Interneuron Connecting the Input and the Output Regions of the Hippocampus

Abstract

The main excitatory pathway of the hippocampal formation is controlled by a network of morphologically distinct populations of GABAergic interneurons. Here we describe a novel type of GABAergic interneuron located in the outer molecular layer (OML) of the rat dentate gyrus with a long-range forward projection from the dentate gyrus to the subiculum across the hippocampal fissure. OML interneurons were recorded in hippocampal slices by using the whole-cell patch-clamp configuration. During recording, cells were filled with biocytin for subsequent light and electron microscopic analysis. Neurons projecting to the subiculum were distributed throughout the entire OML. They had round or ovoid somata and a multipolar dendritic morphology. Two axonal domains could be distinguished: an extensive, tangential distribution within the OML and a long-range vertical and tangential projection to layer 1 and stratum pyramidale of the subiculum. Symmetric synaptic contacts were established by these interneurons on dendritic shafts in the OML and subiculum. OML interneurons were characterized physiologically by short action potential duration and marked afterhyperpolarization that followed the spike. On sustained current injection, they generated high-frequency (up to 130 Hz, 34°C) trains of action potentials with only little adaptation. In situ hybridization and single-cell RT-PCR analysis for GAD67 mRNA confirmed the GABAergic nature of OML interneurons. GABAergic interneurons in the OML projecting to the subiculum connect the input and output regions of the hippocampus. Hence, they could mediate long-range feedforward inhibition and may participate in an oscillating crossregional interneuron network that may synchronize the activity of spatially distributed principal neurons in the dentate gyrus and the subiculum. Key words: GABAergic interneurons; dentate-subicular projection; glutamate decarboxylase; single-cell RT-PCR; feedforward inhibition; dentate gyrus; ratThe neuronal network of the hippocampus consists of glutamatergic principal neurons (granule cells and pyramidal neurons) and GABAergic interneurons (Amaral, 1978;Buhl et al., 1994; Schwartzkroin, 1995a,b) (for review, see Freund and. Although interneurons numerically represent only ϳ10% of the neuronal population, they regulate the activity of the entire network. GABAergic interneurons mediate feedback or feed-forward inhibition by local synaptic interactions with principal neurons and thereby control their activity (Andersen et al., 1963;Buzsáki, 1984). In addition, GABAergic interneurons form a network by mutual synaptic interactions. This interneuron network is thought to be involved in the generation of oscillatory activity and may provide the clock signal for temporal encoding of information in principal neurons (Soltész and Deschênes, 1993;Bragin et al., 1995;Buzsáki and Chrobak, 1995;Cobb et al., 1995;Whittington et al., 1995;Jefferys et al., 1996).The axons of GABAergic interneurons innervate specific regions of their postsynaptic target cells (Somogyi, 1977...

Molecular layer perforant path-associated cells contribute to feed-forward inhibition in the adult dentate gyrus

“…Because the rabies virus completely fills the axons and dendrites of infected neurons with mCherry, it allows us to visualize the detailed morphology of MOPP cells. Outer molecular layer (OML) cells were another cell type found in the MLs in the rat, which had axons that projected across the hippocampal fissure toward the subiculum area (23). It is unlikely that OML cells were labeled because we found that the rabies virus only labeled cells that strictly confined their axons to the ML and we did not see mCherry-labeled axons or cell bodies in the subiculum (Fig.…”

Chronic Ethanol Ingestion FacilitatesN-Methyl-d-aspartate Receptor Function and Expression in Rat Lateral/Basolateral Amygdala Neurons

“…Amplicons were analyzed by agarose gel electrophoresis using ethidium bromide fluorescence. Oligonucleotide primers were derived from unique sequences to specifically amplify individual NR2 subunits (Porter et al, 1998), the 67-kDa form of glutamic acid decarboxylase (Ceranik et al, 1997), or GAPDH (Salazar et al, 1999). All oligonucleotides were obtained from commercial sources (Sigma Genosys, The Woodlands, TX).…”

Neuronal Diversity in GABAergic Long-Range Projections from the Hippocampus

“…Interneurons have been reported with axonal arborization not respecting hippocampal areal boundaries, including the so-called CA1 backprojection cell innervating the CA3 area and the dentate gyrus (Sik et al, 1994), the perforant path associated cells innervating CA1 and subicular pyramidal cells and dentate granule cells (Ceranik et al, 1997;Vida et al, 1998;Klausberger et al, 2005), and the hippocamposubicular cells in the mouse (Losonczy et al, 2002). Overall, at least seven types of GABAergic projection neurons exist in the CA1 area.…”

“…For example, hippocampal GABAergic neurons innervate the medial septum (Alonso and Kohler, 1982) and commissural GABAergic cells interconnect the dentate gyri (Ribak et al, 1986;Leranth and Frotscher, 1987). Other interareal connections include the projection from the presubiculum to the entorhinal cortex (van Haeften et al, 1997) and interregional connections of hippocampal fields (Sik et al, 1994(Sik et al, , 1995Ceranik et al, 1997;Losonczy et al, 2002;Gulyas et al, 2003;Ferraguti et al, 2005). Long-range GABAergic projections have also been described in the isocortex (Gonchar et al, 1995;Manzoni, 1996, 2004;Jinno and Kosaka, 2004;Tomioka et al, 2005).…”