Differences in paired-pulse inhibition and facilitation in the dentate gyrus and CA3 field between dorsal and ventral rat hippocampus.

We studied the processes of inhibition and facilitation in the dentate gyrus (DG) and the CA3 field by examining the effects of paired-pulse stimulation on the evoked population spike (PS) in dorsal (DH) and ventral (VH) hippocampal slices from the adult rat. The antidromic-orthodromic (A-O) and the orthodromic-orthodromic (O-O) paired-pulse stimulation protocols were used at varying inter-pulse intervals (IPI). In the DG, the A-O stimulation produced an early depression of PS lasting 30-40ms which was significantly stronger in the VH compared with DH. The O-O stimulation produced a biphasic pattern of effects, in both dorsal and ventral DG, consisting of an early depression of PS followed by facilitation at relatively longer intervals. In the DH but not the VH the phase of facilitation was followed by a late depression of PS (>200ms). In the CA3 field both A-O and O-O stimulation had a biphasic effect consisting of an early phase of strong depression of similar strength in DH and VH. The depression was followed by a phase of facilitation which was more pronounced with O-O stimulation. The facilitation observed with the O-O stimulation was much stronger in DH than VH and in DH only it was significantly reduced by the antagonist of GABAB receptors CGP52432. Furthermore, the facilitation was insensitive to changes in [Ca(2+)]o in both hippocampal poles. These findings suggest that the dorsal compared with ventral DG is more amenable to fast-frequency input but filters out slow-frequency inputs more reliably while the gating and amplification of the excitatory input in the CA3 circuitry is more prominent in DH than in VH.

Varying magnitude of GABAergic recurrent inhibition enhancement by different sedative/anesthetic agents in dorsal and ventral hippocampus.

The positive modulation of the GABA(A) receptor (GABA(A)R) is presumably one of the main mechanisms by which several sedatives mediate their actions in the central nervous system. This modulation appears to depend on the presence of alpha and beta GABA(A)R subunits, whose distinct expression in dorsal and ventral hippocampus has been recently shown. Using population spike recordings from the CA1 area of dorsal (DHS) and ventral (VHS) hippocampal slices we compared the effects of seven sedative/anesthetic drugs (diazepam, midazolam, phenobarbital, propofol, pentobarbital, thiopental and alfaxalone) on the GABAergic recurrent inhibition (RI) between the two hippocampal poles. The strength and duration of RI was quantified by measuring an antidromic stimulation-induced suppression of the orthodromic population spike at varying inter-pulse intervals. All drugs enhanced RI in both DHS and VHS but high concentrations of barbiturates and alfaxalone prolonged RI considerably more compared to benzodiazepines or low doses of barbiturates and propofol. Furthermore, the drug-induced prolongation of RI was significantly greater in DHS than in VHS. Thus, RI was enhanced by thiopental (50 microM), alfaxalone (2.5 microM) and pentobarbital (50 microM) up to 150 ms, 150 ms and 270 ms respectively in DHS, and up to 70 ms, 100 ms and 150 ms respectively in VHS. In addition, under GABA(B) receptor blockade, thiopental (100 microM) and alfaxalone (10 microM) prolonged GABA(A)R-mediated RI significantly more in DH (up to 900 ms) than in VH (up to 430 ms and 600 ms respectively). This finding provides support to the notion of diversification of intrinsic organization along the septotemporal axis of the hippocampus. Finally, an interesting link was revealed between the magnitude of drug-induced enhancement of RI and the reported sedative potency of the drugs used, suggesting that deep sedation and anesthesia may involve prolongation of GABAergic inhibition.

The GABAA receptor-mediated recurrent inhibition in ventral compared with dorsal CA1 hippocampal region is weaker, decays faster and lasts less.

Hippocampal functions appear to be segregated along the dorso-ventral axis of the structure. Differences at the cellular and local neuronal network level may be involved in this functional segregation. In this study the characteristics of CA1 recurrent inhibition (RI) were measured and compared between dorsal (DH, n = 95) and ventral (VH, n = 60) hippocampal slices, using recordings of suprathreshold field potentials. RI strength was estimated as the percentile decrease of the population spike (PS) amplitude evoked with an orthodromic stimulus (at the Schaffer collaterals) when preceded by an antidromic stimulus (at the alveus). Varying the interpulse interval (IPI) between the two stimuli, we estimated RI duration. Alvear stimulation produced significant PS suppression in both VH and DH at every IPI tested, from 10 to 270 ms. Moreover, gradually more oblique DH (but not VH) slices displayed increasing RI, which at IPIs < or = 125 ms was reversibly abolished by the GABAA receptor antagonist picrotoxin (10 microM). The GABAA-mediated RI, measured under the blockade of GABAB receptors, was weaker, decayed faster and lasted less in VH compared to DH slices, regardless of the slice orientation. Specifically, in VH compared to DH, the PS suppression at 20 ms was 34.4 +/- 4.5% versus 69.9 +/- 6.5% (P < 0.001), the time constant of RI decay was 29 +/- 2.4 versus 87.5 +/- 13.6 ms (P < 0.01) and the duration was 50 versus 125 ms (P < 0.001). Thus, GABAA-mediated RI may control the CA1 excitatory output less effectively in VH compared to DH. The observed dorso-ventral differences in RI contribute to the longitudinal diversification of the structure and may underlie to some extent the region-specificity of hippocampal functions.