Study finds age-related weakening in hippocampus-prefrontal cortex brain circuit in rats
A new study using high-density Neuropixels probes found that aged rats show attenuated polysynaptic and select monosynaptic responses in the medial prefrontal cortex following hippocampal stimulation. The hippocampus-medial prefrontal cortex circuit is known to support spatial working memory and cognitive flexibility, and age-related changes to it have long been suspected but poorly characterized at the circuit level. These findings identify specific vulnerable nodes — particularly the infralimbic cortex and ventral hippocampal inputs — that may underlie age-related cognitive decline.
Researchers recorded field potentials and single-unit activity in the medial prefrontal cortex (mPFC) of young (10–12 month) and aged (23–26 month) male F344 rats using Neuropixels probes while electrically stimulating the intermediate and ventral hippocampus. Both short-latency monosynaptic (5–35 ms) and long-latency polysynaptic (35–100 ms) responses were observed in the prelimbic and infralimbic cortices. In aged rats, direct synaptic transmission from the ventral hippocampus to the infralimbic cortex was reduced, while other monosynaptic connections were largely preserved. Polysynaptic responses — reflecting local mPFC circuit recruitment — were more broadly impaired: aged rats showed both reduced infralimbic field potential amplitudes and diminished evoked firing rates across both mPFC subregions. The nature of the polysynaptic deficit differed by stimulation site, with intermediate hippocampal stimulation reducing the proportion of recruited neurons and ventral hippocampal stimulation reducing firing rates in aged animals. The authors conclude that aging selectively targets ventral hippocampal-prefrontal synaptic transmission and local mPFC circuit dynamics, with the infralimbic cortex being particularly vulnerable, and suggest these deficits may contribute to age-related impairments in cognitive flexibility.
What's missing
The study is limited to male F344 rats, so generalizability to females or other strains and species — including humans — is uncertain. The study does not directly link the observed electrophysiological deficits to behavioral measures of cognitive performance in the same animals, leaving the causal relationship to age-related cognitive decline inferential. It is also unclear whether the observed changes reflect synaptic loss, altered inhibitory tone, or other mechanisms, as no anatomical or molecular analyses were reported.
What different sources said
- bioRxivCenter
Hippocampus-evoked polysynaptic responses in the medial prefrontal cortex are attenuated in aged rats.
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