Differential expression of γ‐aminobutyric acid‐A receptor subunits in rat dorsal and ventral hippocampus

Abstract

Recent data demonstrate weaker gamma-aminobutyric acid (GABA)-ergic inhibition in ventral (VH) compared with dorsal (DH) hippocampus. Therefore, we examined possible differences regarding the GABAA receptors between VH and DH as follows: 1) the expression of the GABAA receptor subunits (alpha1/2/4/5, beta1/2/3, gamma2, delta) mRNA and protein and 2) the quantitative distribution and kinetic parameters of [3H] muscimol (GABAA receptor agonist) binding. VH compared with DH showed: 1) lower levels for alpha1, beta2, gamma2 but higher levels for alpha2 and beta1 subunits in CA1, CA2, and CA3, the differences being more pronounced in CA1 region; in the CA1 region, the mRNA levels of alpha5 were higher, whereas those of alpha4 subunit were slightly lower; in dentate gyrus, the mRNA levels of alpha4, beta3, and delta subunits were significantly lower, presumably suggesting a lower expression of the alpha4/beta3/delta receptor subtype; and 2) lower levels of [3H]muscimol binding, with the lowest value observed in CA1, apparently resulting from weaker binding affinity, insofar as the KD values were higher in VH, whereas the Bmax values were similar between DH and VH. The differences in the subunit expression and the lower affinity of GABAA receptor binding observed predominantly in the CA1 region of VH suggest that the alpha1/beta2/gamma2 GABAA receptor subtype dominates in DH, and the alpha2/beta1/gamma2 subtype prevails in VH. This could underlie the lower GABAA-mediated inhibition observed in VH and, to some extent, explain 1) the higher liability of VH for epileptic activity and 2) the differential involvement of DH and VH in cognitive and emotional processes.

Evidence for connexin36 localization at hippocampal mossy fiber terminals suggesting mixed chemical/electrical transmission by granule cells

“…The differential density of Cx36-puncta in the SL of the ventral vs. dorsal hippocampus implies differential expression of Cx36 in granule cell projecting to these regions, and adds to other differences that have been described in dorsal vs. ventral hippocampus (Papatheodoropoulos and Kostopoulos, 2000, 2002a,b; Papatheodoropoulos et al, 2002, 2005; Sotiriou et al, 2005). Pertinent in this regard are implications of abnormal neuronal gap junctional coupling in initiation, maintenance, and spread of epileptic activity and in hypersynchronous activity associated with seizures (Perez et al, 2000; Pike et al, 2000; Rouach et al, 2002; Traub et al, 2001).…”

Distinct Properties of Long-Term Potentiation in the Dentate Gyrus along the Dorsoventral Axis: Influence of Age and Inhibition

“…This underlines that the magnitude of potentiation does not depend solely on the sheer number of interneurons but rather on the overall excitatory/inhibitory balance. While detailed investigations of dorsovental differences regarding inhibitory processes in the DG are missing, studies in the CA1 region suggest marked differences in GABA A -receptor mediated recurrent inhibition 33 , which are best explained by dorsoventral differential expression of particular subunits, leading to contrasting properties of the synaptic pentameric GABA A -receptor protein complexes 34 . On the other hand, distinct proportions of certain subunits (such as α4, β3 and δ) in extrasynaptic GABA A -receptors could result in dorsoventral differences in tonic inhibition 34, 35 , but our measurements did not provide evidence for this.…”

A Novel α5GABAAR-Positive Allosteric Modulator Reverses Hyperactivation of the Dopamine System in the MAM Model of Schizophrenia

“…In the adult HPC, a5GABA A R are located extrasynaptically, primarily in the dendritic fields of CA1, CA3, dentate gyrus, and subiculum (Sur et al, 1999). In addition, a5GABA A R expression and binding is greater in the ventral HPC, mainly stratum lacunosum-moleculare, in comparison with the dorsal HPC (Sarantis et al, 2008;Sotiriou et al, 2005), suggesting that targeted agonism of this GABA subunit would alter ventral HPC activity selectively. It has been shown that extrasynaptic GABA A receptors mediate tonic inhibitory conductances, at both pyramidal and dentate granule cells (Bai et al, 2001;Nusser and Mody, 2002).…”