Immunoreactivity for the GABAA Receptor  1 Subunit, Somatostatin and Connexin36 Distinguishes Axoaxonic, Basket, and Bistratified Interneurons of the Rat Hippocampus

Abstract

Parvalbumin (PV)-expressing interneurons synchronize cortical neurons through gamma-aminobutyric acidergic (GABAergic) synapses. Three types of PV-containing interneurons populate stratum pyramidale of the hippocampal CA1 area: basket cells targeting somata and proximal dendrites, axoaxonic cells innervating axon initial segments, and bistratified cells targeting the dendrites of pyramidal cells. We tested whether this axonal specialization is accompanied by a differential expression of molecules involved in neuronal signaling. Immunofluorescence evaluation of interneurons labeled by neurobiotin in vivo shows that axoaxonic cells express significantly less GABA(A) receptor alpha1 subunit in the plasma membrane than basket and bistratified cells. Electron microscopic immunogold labeling reveals that this subunit contributes heavily to extrasynaptic receptors providing a substrate for tonic inhibition. Results from additional immunofluorescence experiments were consistent with the finding that only bistratified cells express the neuropeptide somatostatin. From the molecular profiles, we estimate that basket, bistratified, and axoaxonic cells represent about 60%, 25%, and 15%, respectively, of PV-containing cells in CA1 stratum pyramidale. In addition, all 3 interneuron classes form connexin36-immunopositive dendrodendritic gap junctions. The differential expression of signaling molecules and the relative frequency of cells reflect the specialized temporal contribution of the 3 types of PV-positive interneurons to GABA release in the network.

Ultrastructure of Synapses in the Mammalian Brain

“…They are constituted from 19 different subunit proteins, allowing for enormous heterogeneity (Luscher and Keller 2004;Tretter and Moss 2008). Immunogold EM shows that GABA A receptors concentrate at synapses Bergersen et al 2003;Baude et al 2007;Masugi-Tokita and Shigemoto 2007), but extrasynaptic receptors are also present and may be functionally significant. The number of GABA A receptors at a synapse (which varies considerably) is directly related to the magnitude of the inhibitory postsynaptic current (Nusser et al 1997).…”

Theta Phase Classification of Interneurons in the Hippocampal Formation of Freely Moving Rats

“…Anatomically, hippocampal interneurons can be divided into many classes (Freund and Buzsáki, 1996) and into additional classes according to whether cells express certain molecules (McBain and Fisahn, 2001;Baude et al, 2007;Fuentealba et al, 2008). An initial functional classification was made by determining the pattern of interneuron discharge relative to sharp-wave activity during sleep .…”

“…Anatomically, hippocampal interneurons are a diverse group; their cell bodies are distributed throughout the layers of Ammon's horn, with widespread, varied dendritic trees and axonal ramifications (Amaral and Wittner, 1995;Freund and Buzsáki, 1996;Klausberger and Somogyi, 2008). Interneurons can be classified on molecular as well as anatomical grounds (McBain and Fisahn, 2001;Klausberger et al, 2003Klausberger et al, , 2004Klausberger et al, , 2005Mott and Dingledine, 2003;Ferraguti et al, 2005;Somogyi and Klausberger, 2005;Baude et al, 2007;Jinno et al, 2007;Tukker et al, 2007;Fuentealba et al, 2008).…”

Bridging the Gap – Understanding the Role of Gap Junctions in Seizures

“…Connexin36 gap junctions are not expressed uniformly across all interneuron classes. Rather, two main expression patterns predominate: that between same-class parvalbumin-containing multipolar-bursting (MB) cells (Deans et al 2001;Liu and Jones 2003;Markram et al 2004;Baude et al 2007), which synapse onto pyramidal cells in the region of the soma or proximal dendrites (Deans et al 2001;Liu and Jones 2003;Markram et al 2004); and that between multipolar calretinin-positive (MCR) and MB interneurons (see Fig 2). The effect on global brain dynamics of a disruption to gap junction connectivity within these inhibitory networks is not intuitively obvious.…”