IMR Press / JIN / Volume 21 / Issue 1 / DOI: 10.31083/j.jin2101006
Open Access Original Research
The effect of insulin receptor deletion in neuropeptide Y neurons on hippocampal dependent cognitive function in aging mice
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1 School of Psychology, UNSW Sydney, 2052 Sydney, Australia
2 Garvan Institute of Medical Research, 2010 Darlinghurst, Australia
*Correspondence: (Denovan P. Begg)
J. Integr. Neurosci. 2022, 21(1), 6;
Submitted: 29 April 2021 | Revised: 29 July 2021 | Accepted: 27 August 2021 | Published: 28 January 2022
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Insulin is known to act in the central nervous system to regulate several physiological and behavioural outcomes, including energy balance, glucose homeostasis and cognitive functioning. However, the neuronal populations through which insulin enhances cognitive performance remain unidentified. Insulin receptors are found in neuropeptide-Y (NPY) expressing neurons, which are abundant in the hypothalamus and hippocampus; regions involved in feeding behaviour and spatial memory, respectively. Here we show that mice with a tissue specific knockout of insulin receptors in NPY expressing neurons (IRlox/lox; NPYCre/+) display an impaired performance in the probe trial of the Morris Water Maze compared with control mice at both the 6 and the 12, but not at the 24 months time point, consistent with a crucial role of insulin and NPY in cognitive functioning. By 24 months of age all groups demonstrated similar reductions in spatial memory performance. Together, these data suggest that the mechanisms through which insulin influences cognitive functioning are, at least in part, via insulin receptor signaling in NPY expressing neurons. These results also highlight that cognitive impairments observed in aging may be due to impaired insulin signaling.

Insulin receptors
Spatial memory
Morris Water Maze
Fig. 1.
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