Distinct roles of basal forebrain cholinergic neurons in spatial and object recognition memory

Abstract

Recognition memory requires processing of various types of information such as objects and locations. Impairment in recognition memory is a prominent feature of amnesia and a symptom of Alzheimer’s disease (AD). Basal forebrain cholinergic neurons contain two major groups, one localized in the medial septum (MS)/vertical diagonal band of Broca (vDB), and the other in the nucleus basalis magnocellularis (NBM). The roles of these cell groups in recognition memory have been debated, and it remains unclear how they contribute to it. We use a genetic cell targeting technique to selectively eliminate cholinergic cell groups and then test spatial and object recognition memory through different behavioural tasks. Eliminating MS/vDB neurons impairs spatial but not object recognition memory in the reference and working memory tasks, whereas NBM elimination undermines only object recognition memory in the working memory task. These impairments are restored by treatment with acetylcholinesterase inhibitors, anti-dementia drugs for AD. Our results highlight that MS/vDB and NBM cholinergic neurons are not only implicated in recognition memory but also have essential roles in different types of recognition memory.

Acetylcholine modulates gamma frequency oscillations in the hippocampus by activation of muscarinic M1 receptors

“…In this study we reveal that the neuromodulator acetylcholine modulates the power but not frequency of gamma oscillations in the hippocampus. This mechanism could work in tandem with the modulation of theta oscillations to mediate the effects of acetylcholine on cognition (Lee et al ., ; McGaughy et al ., ; Vandecasteele et al ., ; Okada et al ., ). Indeed optogenetically induced acetylcholine release enhances theta and gamma power in the hippocampus of anaesthetised mice, but reduces power in both bands in awake mice (Vandecasteele et al ., ).…”

Cholinergic modulation of spatial learning, memory and navigation

“…Therefore, we expect that improving our anatomical understanding of BF structures, cell type and subregion specific inputs and outputs and differences in local connectivity using novel viral labelling techniques including monosynaptic rabies tracing or cTRIO (Beier et al., ; Schwarz et al., ) will improve our abilities of spatially specific targeting of the BF. New insights may also arise using promising alternatives to the 192‐IgG saporin lesioning such as the use of immunotoxin in transgenic animals (Okada et al., ). Optogenetic methods could further increase spatial specificity compared to the limited possibilities of local drug injections or localised lesioning approaches (Siegle & Wilson, ).…”

“…Also dependent on spatial working memory, animals with cholinergic lesions to the MS perform poorly on this task (Fitz, Gibbs, & Johnson, ; Johnson, Zambon, & Gibbs, ; Walsh, Herzog, Gandhi, Stackman, & Wiley, ). The MS cholinergic system is also involved in object location memory, evidenced by impaired performance on object location recognition in lesioned animals (Cai, Gibbs, & Johnson, ; Okada, Nishizawa, Kobayashi, Sakata, & Kobayashi, ).…”

Decreased vesicular acetylcholine transporter related to memory deficits in epilepsy: A [18F] VAT positron emission tomography brain imaging study

“…To the best of our knowledge, our study is the first to report basal forebrain cholinergic neuronal injury in an epilepsy model. Basal forebrain cholinergic neurons are major components of Ch1‐Ch4 sectors innervating the hippocampus and cortex, which play a significant part in spatial and working memory . In a previous report, elimination of VAChT in basal forebrain caused deficits in spatial memory, long‐term potentiation, which indicates the specific contribution of forebrain cholinergic tone for modulating cognition.…”

“…Basal forebrain cholinergic neurons are major components of Ch1-Ch4 sectors innervating the hippocampus and cortex, which play a significant part in spatial and working memory. 32 In a previous report, elimination of VAChT in basal forebrain caused deficits in spatial memory, long-term potentiation, 33 which indicates the specific contribution of forebrain cholinergic tone for modulating cognition. Nevertheless, whether basal forebrain neuronal dysfunction plays a part in epilepsy-associated cognitive Concerning the caudate and putamen region, our results did not reveal correlation between level of VAChT and memory function.…”