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The role of acetylcholine in learning: Cholinergic MSDB lesions retard trace eyeblink conditioning and decrease adult neurogenesis

Anderson ML, Nokia MS, Shors TJ (2014) The role of acetylcholine in learning: Cholinergic MSDB lesions retard trace eyeblink conditioning and decrease adult neurogenesis. Neuroscience 2014 Abstracts 177.10. Society for Neuroscience, Washington, DC.

Summary: Decades ago, acetylcholine was considered intrinsic to processes related to attention and/or learning and memory. However, in the last decade or so, this relationship has been questioned and with good reason. That said, only a few studies have addressed the involvement of acetylcholine in tasks that require an animal to associate stimuli separated in time, such as trace eyeblink conditioning. Trace eyeblink conditioning is associated with hippocampal theta rhythmic activity and dependent on adult neurogenesis in the hippocampus, both of which are thought to be mediated by cholinergic activity. In the present study, 192 IgG-Saporin (SAP) was infused into the medial septum diagonal band (MSDB) complex of Sprague-Dawley rats to selectively kill cholinergic neurons bilaterally or unilaterally. Each side of the MSDB predominantly projects to the ipsilateral hippocampal formation. Animals were considered to have a bilateral lesion if the number of neurons that express choline acetyltransferase was reduced by at least 80% compared to sham animals or a unilateral lesion if the difference in the reduction between hemispheres was greater than 30%. Animals with bilateral, unilateral or sham lesions were trained with trace eyeblink conditioning at least 14 days after the SAP infusion. Animals were given 200 trials for four days for 800 trials in total. Animals with a sham lesion made more conditioned responses over all 800 trials compared to animals with bilateral and unilateral lesions. Conditioned responses increased over time in all groups. Taken together, bilateral and unilateral lesions both retard but do not drastically impair learning. In two separate experiments, the effect of bilateral and unilateral lesions on adult neurogenesis and theta rhythms was assessed. Animals were injected with 5-bromo-2’-deoxyuridine (BrdU) to label dividing cell at least 14 days after the SAP infusion. Seven days later, the number of BrdU-positive cells in the dentate gyrus of the hippocampus of animals with bilateral and unilateral lesions was reduced by ~40% in both hemispheres. Hippocampal local field potentials were recorded from another group of animals. Seven days following the SAP infusion, relative theta power was reduced in the bilateral but not unilateral group. However, by Day 14 relative theta power was similar in all three groups. This data suggests that a reduction in the number of new neurons in the hippocampus may be a contributing factor to a trace learning deficit as a result of a MSDB lesion. Moreover, disrupting septohippocampal cholinergic activity even in one hemisphere only is enough to reduce hippocampal adult neurogenesis and retard learning.

Related Products: 192-IgG-SAP (Cat. #IT-01)