Reversible inactivation of the nucleus basalis magnocellularis induces disruption of cortical acetylcholine release and acquisition, but not retrieval, of aversive memories

Abstract

The basal forebrain complex, which includes the nucleus basalis magnocellularis (NBM), provides widespread cholinergic and ␥-aminobutyric acid-containing projections throughout the brain, including the insular and pyriform cortices. A number of studies have implicated the cholinergic neurons in the mediation of learning and memory processes. However, the role of basal forebrain activity in information retrieval mechanisms is less known. The aim of the present study is to evaluate the effects of reversible inactivation of the NBM by tetrodotoxin (TTX, a voltagesensitive sodium channel blocker) during the acquisition and retrieval of conditioned taste aversion (CTA) and to measure acetylcholine (ACh) release during TTX inactivation in the insular cortex, by means of the microdialysis technique in free-moving rats. Bilateral infusion of TTX in the NBM was performed 30 min before the presentation of gustative stimuli, in either the CTA acquisition trial or retrieval trial. At the same time, levels of extracellular ACh release were measured in the insular cortex. The behavioral results showed significant impairment in CTA acquisition when the TTX was infused in the NBM, whereas retrieval was not affected when the treatment was given during the test trial. Biochemical results showed that TTX infusion into the NBM produced a marked decrease in cortical ACh release as compared with the controls during consumption of saccharin in the acquisition trial. Depleted ACh levels were found during the test trial in all groups except in the group that received TTX during acquisition. These results suggest a cholinergic-dependent process during acquisition, but not during memory retrieval, and that NBM-mediated cholinergic cortical release may play an important role in early stages of learning, but not during recall of aversive memories.The cerebral cortex has been considered as the ubiquitous place for the storage of long-term memory. In this regard, a great deal of investigation into brain health has focused on a particular central nervous system disorder, Alzheimer's disease. This disease results, at least in part, from a deficit in acetylcholine (ACh) neurotransmission caused by a degeneration of large basal forebrain (BF) cholinergic neurons and a deficit in choline acetyltransferase, the enzyme that synthesizes ACh (1).Accumulative evidence supports the role of cholinergic neurons in the BF in processes such as arousal, attention, learning, and memory. Behavioral deficits associated with lesions produced by injections of excitatory amino acid agonists into the nucleus basalis magnocellularis (NBM) have been demonstrated in a variety of tasks (2, 3). However, the behavioral deficits of these lesions might be caused not only by the resulting cholinergic deafferentation, because 30-35% of the population of BF projections neurons to the cortex are ␥-aminobutyric acid-containing neurons (4-6).In this regard, there are several experiments trying to study more directly the modulatory role of ACh in the activity of cortical ...

Cholinergic Control in Developing Prefrontal–Hippocampal Networks

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Glutamatergic activity in the amygdala signals visceral input during taste memory formation

“…Among the structures involved in the initial phases of taste memory formation are the gustatory neocortex and amygdala (8). Thus, damage to either the gustatory insular cortex (IC) or amygdala in adult rats leads to impaired acquisition of CTA (6,7,(9)(10)(11)(12)(13)(14)(15)(16)(17). However, the functional roles of IC and amygdala seem to be different during the phases of taste memory formation.…”

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