Differential expression of γ-aminobutyric acid-a receptor subunits in rat dorsal and ventral hippocampus

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 GABA(A) receptors between VH and DH as follows: 1) the expression of the GABA(A) receptor subunits (alpha 1/2/4/5, beta 1/2/3, gamma 2, 8) mRNA and protein and 2) the quantitative distribution and kinetic parameters of [H-3]muscimol (GABAA receptor agonist) binding. VH compared with DH showed: 1) lower levels for alpha 1, beta 2, gamma 2 but higher levels for alpha 2 and beta 1 subunits in CA1, CA2, and CA3, the differences being more pronounced in CA1 region; in the CA1 region, the mRNA levels of alpha 5 were higher, whereas those of alpha 4 subunit were slightly lower; in dentate gyrus, the mRNA levels of alpha 4, beta 3, and delta subunits were significantly lower, presumably suggesting a lower expression of the alpha 4/beta 3/delta receptor subtype; and 2) lower levels of [H-3]muscimol binding, with the lowest value observed in CA1, apparently resulting from weaker binding affinity, insofar as the K-D values were higher in VH, whereas the B-max 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 alpha 1/beta 2/gamma 2 GABAA receptor subtype dominates in DH, and the alpha 2/beta 1/gamma 2 subtype prevails in VH. This could underlie the lower GABA(A)-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. (c) 2005Wiley-Liss, Inc.