Cholecystokinin modulates age-dependent Thalamocortical Neuroplasticity

The thalamocortical pathway exhibits neuroplasticity not only during the critical period but also in adulthood. Here, we aimed to investigate the modulation of age-dependent thalamocortical plasticity by cholecystokinin (CCK). Our findings revealed the expression of CCK in thalamocortical neurons, and high-frequency stimulation (HFS) of the thalamocortical pathway elicited the release of CCK in auditory cortex (ACx), as evidenced by CCK sensor. HFS of the medial geniculate body (MGB) induced thalamocortical long-term potentiation (LTP) in wildtype young adult mice. However, knockdown of Cck expression in MGB neurons or blockade of the CCK-B receptor (CCKBR) in ACx effectively abolished HFS-induced LTP. Notably, this LTP could not be elicited in both juvenile mice (week 3) and mice over 18 months old, due to the absence of CCKBR in juvenile mice and the inability of CCK to be released in aged mice. Remarkably, the administration of exogenous CCK into the auditory cortex of the aged mice restored this LTP, accompanied by a significant improvement in frequency discrimination. These findings suggest the potential of CCK as a therapeutic intervention for addressing neurodegenerative deficits associated with thalamocortical neuroplasticity.