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Acetylcholine in learning and memory

$1,888,011ZIAFY2021NSNIH

National Institute Of Neurological Disorders And Stroke

Investigators

Linked publications, trials & patents

Abstract

Our first major objective for the current year was to get the Laboratory of Circuits, Synapses and Molecular Signaling up and running within the NINDS IRP at the Bethesda campus of NIH. We have now officially opened the lab with the delivery of our final piece of major equipment in March of 2021! Between logistic delays combined with the loss of personnel x time on-site due to the COVID pandemic, - we have only just begun to establish the laboratory research program and working as a group (Major Objective 2). Sub-objective 1: Oct 2020 - March 2021: Set up the physical space. Renovations were largely completed during subsequent COVID shutdowns, with major equipment installation and training complete by March of 2021. Sub-objective 2: recruit and train key lab personnel (ongoing). The lab now includes 2 Staff scientists, 3 post-doctoral fellows, 1 clinical fellow, 1 post-bac trainee, 1 research scientist and 1 biologist. Training and interactions have been largely remote. Sub-objective 3: Equip and supply the lab. (completed) The final arrival of key major equipment purchases was completed in March 2021. Sub-objective 4: Establish our mouse colony (ongoing). Genetically modified mice lines that we had developed at prior universities have now undergone rederivation at the NIH. We have supplemented these lines with obtaining commercially available mice with genetically encoded probes to the extent possible. We have just begun to establish a self-sustaining breeding colony including the generation of multi-transgenic lines. Our second major objective was to begin our research projects. We have now begun to have mice at the NIH to study and to generate data relevant to the memory project in the lab. We have re-generated/modified an array of genetically encoded probes - both cholinergic specific and activity dependent. Continued viral development, with the collaboration of Dr. Talmage ( NINDS) and help of Dr. Fields in the NINDS Viral Core, are ongoing for selective labeling of cholinergic neurons independent of species. Certain aspects of the memory project also involved continued collaboration with individuals at Universities that were operational and as such, we were able to complete and submit multiple manuscripts. In particular we were able to foster and sustain ongoing collaborations with Dr. Talmage, NINDS IRP and Dr. Ari Kaufman (Department of Computer Sciences) and Drs. Parsey and De Lorenzo (Department of Psychiatry)(all at Stony Brook University) and with Dr. Marina Picciotto at Yale University Department of Psychiatry. The collaboration with Dr. Talmage and (a) Dr. Kaufman yielded two publications (developing unique image process algorithms that use AI approaches to predict trajectories of cholinergic terminal field loss during aging), (b) Drs Parsey and De Lorenzo the establishment of a cross species study of the cholinergic system during normal and pathological aging (publications pending) and (c) with Dr. Picciotto and colleagues publication of two studies identifying specific populations of cholinergic neurons that participate in distinct types of memory and demonstrate for the first time that cholinergic neurons participate directly in memory engrams.

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