Modulation of spatial memory and expression of hippocampal neurotransmitter receptors by selective lesion of medial septal cholinergic and GABAergic neurons

Corticosterone mediates the deleterious effect of medial septal inactivation on memory retrieval.

“…Based on this evidence, it is possible that after muscimol administration in the medial septum, a disinhibition of these hippocampal GABAergic interneurons occurs, which in turns creates a net inhibitory effect on the pyramidal cells of this region, decreasing glutamatergic release in the hippocampus. It is well known that this glutamatergic release is important for the recovery of spatial memory (Dashniani et al, 2020), supporting the relation between intraseptal muscimol administration and the memory impairment observed in the present study.…”

“…Thereby, muscimol injections in the medial septum could reduce cholinergic transmission to hippocampal pyramidal cells, resulting in decreased glutamatergic transmission, and disrupting synaptic plasticity mechanisms associated with memory (Gulledge & Kawaguchi, 2007; Kanju et al, 2012). Nevertheless, recent studies have shown that selective lesions of the cholinergic component of the septo-hippocampal projection are associated with limited deficits (Frick et al, 2004; Kirby & Rawlins, 2003) or no deficit in the long-term retrieval of spatial memory (Dashniani et al, 2020). These results suggest that the cholinergic projection of the septum to the hippocampus would be more involved in the flexibility of the expression of memory in the face of environmental changes, than in the recovery of information (Ikonen et al, 2002; Parent & Baxter, 2004).…”

“…This is especially true when the retrieval is tested after a long delay (Nagahara & McGaugh, 1992). In addition, specific lesions of the GABAergic projections impair only the retention of the platform location (Dashniani et al, 2020).…”

“…In particular, we sought to determine whether the temporal inhibition of the medial septum, followed by the systemic administration of corticosterone, would have a summative effect evidenced by a more severe deficit in the retrieval of spatial memory than the one expected when these treatments are administered individually. Opposite to previous studies where the medial septum is lesioned or inactivated before the acquisition of spatial tasks (Brioni et al, 1990; Dashniani et al, 2020; Lecourtier et al, 2011), in this study the intraseptal injection of muscimol was performed before the retrieval test in the Barnes maze to ensure that the septal inactivation would not affect the acquisition or consolidation of the task.…”

Modulation of prefrontal cortex function by basal forebrain cholinergic and GABAergic neurons at the behavioral and molecular level

“…It can be assumed that after NBM cholinergic lesions the spatial memory deficit in the present study is associated with decreased cholinergic activity in the hippocampus. However, other reports using selective immunotoxic lesions of medial septal cholinergic projecting neurons revealed mild or no spatial memory deficits [10,11], indicating that cholinergic deprivations alone are not sufficient to induce impairments of hippocampal-dependent spatial learning or memory. Accordingly, the spatial memory deficit as a result of cholinergic NBM lesions may be associated with an alteration in cholinergic transmission in the mPFC.…”