| Summary: | 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.
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