Elucidating the Role of Cerebellar Nuclei Parvalbumin Activity on Adolescent Reversal Learning

The cerebellar nuclei (CN) play a part in cognitive behavior through the cerebello-cortico circuit. However, the impact of critical period mechanisms and their influence on cognitive behavior, like parvalbumin (PV) expressing interneurons within perineuronal nets (PNNs), remains uncertain. To explore this, researchers studied the lateral CN (LCN) PV cell calcium activity during a visual discrimination touchscreen task in adolescent mice.

At postnatal day 21 (P21), the mice were given the GCaMP6f calcium indicator. The LCN's critical period was manipulated in male mice using inhibitory Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) from P21 to P35 or by injecting an Hapln1-AAV vector to specifically target LCN PNN development. After completing the task, cerebellar tissue was analyzed for viral recovery and antibody staining for PNN components, Hapln1, and aggrecan.

The study's outcomes indicated that DREADD-treated mice exhibited enhanced reversal learning, higher calcium responses to learning-related activity, and altered PNN expression (Hapln1 and aggrecan). Conversely, Hapln1-treated mice displayed reduced final day acquisition performance, poorer reversal performance compared to DREADD groups, diminished reversal calcium learning-related activity, and increased PNN expression (Hapln1).

In summary, these findings underscore the role of LCN mechanisms in learning and emphasize the necessity of understanding region-specific critical periods of plasticity.