Medial Septum-Diagonal Band of Broca (MSDB) GABAergic Regulation of Hippocampal Acetylcholine Efflux Is Dependent on Cognitive Demands

Abstract

The septohippocampal pathway contains cholinergic, GABAergic, and glutamatergic projections and has an established role in learning, memory, and hippocampal theta rhythm. Both GABAergic and cholinergic neurons in the medial septum-diagonal band of Broca (MSDB) have been associated with spatial memory, but the relationship between the two neuronal populations is not fully understood. The present study investigated the effect of selective GABAergic MSDB lesions on hippocampal acetylcholine (ACh) efflux and spatial memory during tasks that varied in memory demand. Male Sprague Dawley rats were given GABAergic lesions of the MSDB using GAT1-saporin (GAT1-SAP) and examined on spontaneous exploration (Experiment 1) and non-matching to position without (NMTP; Experiment 2) and with a delay (DNMTP; Experiment 3), while concurrently using in vivo microdialysis to measure hippocampal ACh efflux. Intraseptal GAT1-SAP treatment did not alter baseline or behaviorally stimulated hippocampal ACh efflux or maze exploration (Experiment 1). Moreover, GAT1-SAP did not alter evoked hippocampal ACh efflux related to NMTP nor did it impair working memory in NMTP (Experiment 2). In contrast, both ACh efflux and performance in DNMTP were impaired by intraseptal GAT1-SAP. Thus, GABAergic MSDB neurons are important for spatial working memory and modulate hippocampal ACh efflux under conditions of high memory load. The relationship between the septohippocampal cholinergic and GABAergic systems and working memory will be discussed.

Central relaxin-3 receptor (RXFP3) activation increases ERK phosphorylation in septal cholinergic neurons and impairs spatial working memory

“…Cholinergic neuron activity is, thus, necessary for the transition from inactive to active hippocampal-related behavior, but is inefficient in inducing significant change in the activity of the hippocampal neurons during arousal states (Mamad et al 2015). Moreover, optogenetic activation of septal cholinergic neurons increases hippocampal activity within the theta band (2-6 Hz) in anesthetized mice (Vandecasteele et al 2014), and exploratory tasks have been reported to increase AchC in hipoccampus (Roland et al 2014).…”

Basal Forebrain Cholinergic Circuits and Signaling in Cognition and Cognitive Decline

“…Cholinergic signaling from the MS and DB to the hippocampus is certainly important for formation of spatial memories: ACh has consistently been shown by microdialysis to be elevated in the hippocampus during performance of various memory tasks (Mitsushima et al, 2013; Roland et al, 2014; Stanley et al, 2012), and numerous studies have probed the effects of exogenous – and more recently endogenous - ACh on hippocampal plasticity and performance in spatial memory tasks (Cobb and Davies, 2005; Kutlu and Gould, 2016). Blockade of mAChR signaling locally in the hippocampus impairs memory (Carli et al, 1997; Wallenstein and Vago, 2001).…”

The role of NPY in learning and memory

“…Spatial memory is akin to episodic memory, and strictly depends on the hippocampus for consolidation and retrieval (Moscovitch et al, 2005). Moreover, hippocampus-dependent spatial and discriminative learning and memory also involve the basal forebrain (Roland et al, 2014), a prominent source of cholinergic input to the medial temporal lobe (Damasio et al, 1985). This includes the areas containing the medial septal-diagonal band of Broca involved in temporal associations and the nucleus basalis for sustained attention (Mesulam et al, 1983;Olton et al, 1988).…”