The memory-impairing effects of septal GABA receptor activation involve GABAergic septo-hippocampal projection neurons

Abstract

Septal infusions of the ␥-aminobutyric acid (GABA) A agonist muscimol impair memory, and the effect likely involves the hippocampus. GABA A receptors are present on the perikarya of cholinergic and GABAergic septo-hippocampal (SH) projections. The current experiments determined whether GABAergic SH projections are involved in the memory-impairing effects of septal GABA A receptor activation. Experiment 1 tested whether combining septal co-infusions of subeffective doses of muscimol with scopolamine, a drug that selectively influences GABA SH projections, would produce memory deficits. Experiment 2 tested whether hippocampal infusions of a GABA A receptor antagonist would block the effects of septal muscimol infusions. Fifteen minutes prior to assessing spontaneous alternation (SA) or training in a multiple trial inhibitory avoidance (CMIA) task, male Sprague-Dawley rats were given septal infusions of vehicle, muscimol, scopolamine, or co-infusions of muscimol with scopolamine, or septal infusions of vehicle or muscimol combined with hippocampal infusions of vehicle or bicuculline. Septal co-infusions of muscimol with scopolamine significantly impaired SA and CMIA. Hippocampal bicuculline infusions blocked deficits produced by septal muscimol infusions in SA and attenuated deficits produced in CMIA. Combined, these findings suggest that GABAergic SH projections are involved in the memory-impairing effects of septal GABA receptor activation.

Involvement of dorsal hippocampal muscarinic cholinergic receptors on muscimol state-dependent memory of passive avoidance in mice

“…Also medial septum is connected to the hippocampus via the fimbria fornix, which is composed primarily of cholinergic and GABAergic projection neurons (Lewis et al, 1967;Freund and Buzsáki, 1996;Krebs-Kraft et al, 2007).…”

Hippocampal Extracellular Signal-Regulated Kinase Signaling has a Role in Passive Avoidance Memory Retrieval Induced by GABAA Receptor Modulation in Mice

“…For example, the g-aminobutyric acid type A (GABA A ) receptor antagonists including bicuculline (GABA-binding site) and flumazenil (benzodiazepine-binding site) enhance (Brioni and McGaugh, 1988;Castellano and Pavone, 1988;Herzog et al, 1996;Luft et al, 2004;Matsuyama et al, 2008) or impair (Nabeshima et al, 1988;Chrobak and Napier, 1991) memory formation depending on the study. GABA A receptor agonists, including muscimol (GABA-binding site) and diazepam (benzodiazepine-binding site), impair learning (Chrobak et al, 1989) and memory McGaugh, 1989, 1990;Shah and Parent, 2003;Krebs-Kraft et al, 2007;Kim et al, 2009). These findings suggest that the GABA A receptor has an important role in learning and memory.…”

Blocking GABA-A receptors in the medial septum enhances hippocampal acetylcholine release and behavior in a rat model of diencephalic amnesia

“…Furthermore, there is some evidence that the behavioral effects of activation of MS GABA A receptors are further modulated by the action of GABA in the hippocampus. When animals were given septal muscimol (GABA A agonist) combined with hippocampal bicuculline (GABA A antagonist), the memory impairing effects normally produced by septal muscimol were attenuated (Krebs-Kraft et al, 2007). However, this study does not rule out the possibility that MS GABA A receptor activation also influences cholinergic projection neurons.…”