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.
Highlights
IntroductionMemory are inconsistent between studies[19,20,22,23,24,25,26], NBM ablation does not appear to alter mnemonic function[19,26,27]
Memory are inconsistent between studies[19,20,22,23,24,25,26], NBM ablation does not appear to alter mnemonic function[19,26,27]. It remains uncertain how basal forebrain cholinergic cell groups are involved in recognition memory. 192-IgG saporin toxicity seems to be accompanied by the loss of noncholinergic neurons and extensive tissue damage in the basal forebrain under certain conditions[19,21,25,26]
Object reference memory was not altered in the IT-injected Tg mice into either the MS/ vDB or the NBM. These results demonstrate that selective elimination of cholinergic neurons in the MS/ vDB but not the NBM results in impaired spatial recognition memory in the reference memory task, while elimination of the MS/vDB or NBM neurons does not influence object recognition memory in the same task
Summary
Memory are inconsistent between studies[19,20,22,23,24,25,26], NBM ablation does not appear to alter mnemonic function[19,26,27] It remains uncertain how basal forebrain cholinergic cell groups are involved in recognition memory. We used immunotoxin (IT)-mediated cell targeting to address the role of basal forebrain cholinergic neurons in recognition memory. This targeting enables selective elimination of target cell types based on the specificity of a recombinant IT, anti-Tac(Fv)-PE3828,29. Elimination of MS/vDB cholinergic neurons impaired spatial but not object recognition memory in both the reference and working memory tasks. Our results indicate that MS/vDB and NBM neurons possess important roles in distinct types of recognition memory
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