Hyperpolarizing synaptic potentials evoked in CA1 pyramidal cells by glutamate stimulation of interneurons from the oriens/alveus border of rat hippocampal slices. II. sensitivity to GABA antagonists

Abstract

The receptor type mediating the inhibitory postsynaptic potentials (glut-IPSPs), recorded in CA1 pyramidal cells, as a result of glutamate stimulation of interneurons in stratum oriens near the alveus (O/A) was assessed and compared to the type mediating recurrent IPSPs evoked by recurrent activation of interneurons through glutamate stimulation of pyramidal cells in stratum pyramidale (PYR). In response to repetitive electrical stimulation, the peak amplitude of both the O/A glut-IPSP and the PYR glut-IPSP was attenuated (n = 5) in parallel to the reduction in amplitude of the early and late components of the electrically evoked response (stimulus-evoked disinhibition). This suggested the involvement of GABAergic receptors and attested that the interneurons activated during glut-IPSPs were also involved in the circuitry of the electrically evoked IPSPs. The local application of the selective GABAA antagonist bicuculline (100-200 microM) to the slice resulted in a significant reduction in the amplitude of both the O/A (by 76.5%; n = 9) and PYR (by 86.2%; n = 5) glut-IPSPs, in parallel to a decrease of the electrically evoked early IPSP, but not of the late IPSP. The presence of the GABAB antagonist 2-hydroxy-saclofen (1 mM) was able to significantly reduce the amplitude of the O/A glut-IPSPs (by 27.5%; n = 7) and of the electrically evoked late IPSP, but not the PYR glut-IPSP (n = 3). Although the application of phaclofen (20 mM) to the slice reduced the amplitude of the O/A glut-IPSPs (n = 3), the reduction was not statistically significant. These results suggest that recurrent IPSPs elicited from activation of interneurons by stimulation of pyramidal cells are mediated solely via GABAA receptors. Inhibitory postsynaptic potentials elicited from stimulation of interneurons in O/A were also mediated mostly by GABAA receptors, but in addition, displayed a minor component mediated by GABAB receptors. Therefore, since a large proportion of interneurons in O/A are recurrently excited by pyramidal cells (Lacaille J-C et al., 1987, J Neurosci 7: 1979-1993), and since recurrent IPSPs appeared mediated by GABAA receptors, a subpopulation of interneurons activated from O/A might exist that do not receive recurrent excitation but can inhibit pyramidal cells via GABAB receptors.

Interaction of nucleus reuniens and entorhinal cortex projections in hippocampal field CA1 of the rat

“…7, the excitatory RE and EC innervation of several classes of interneurons provides potentially a powerful inhibitory influence covering the entire depth of field CA1. RE 14 has been shown to drive vertical oriens/alveus (O/A) cells, mediating feedforward perisomatic inhibition of CA1 cells (Lacaille et al 1987;Samulack et al 1993;McBain et al 1994;Dolleman-van der Weel et al 1997). …”

Facilitating pyramid to horizontal oriens‐alveus interneurone inputs: dual intracellular recordings in slices of rat hippocampus

“…A pyramidal cell directly excites a horizontal O-A interneurone, which could in turn suppress inputs from the entorhinal cortex to that pyramidal cell and its neighbours by shunting current in distal dendrites. Although preliminary studies (Samulack & Lacaille, 1993;Yanovsky et al 1997) indicate that both GABAA and GABAB receptors are involved in the inhibition of distal pyramidal dendrites by these interneurones, the detailed properties of these inhibitory connections in s. lacunosum moleculare remain to be determined. Clearly, however, the synchronous high frequency discharge in a population of pyramidal cells that occurs, for example, during theta rhythm, would greatly facilitate recruitment of these interneurones and in turn modify entorhinal cortex input to CA1.…”

Depression Viewed as a GABA/Glutamate Imbalance in the Central Nervous System

“…GABA B receptors are expressed on nerve endings of pyramidal neurons exerting the inhibitory effect on glutamatergic transmission (Forti et al, 1997;Samulack et al, 1993), therefore their blockade will cause an overflow of glutamate [ Fig. 5 (1)] leading to stimulation of the inhibitory GABAergic neuron.…”