| First Author | Evrard MR | Year | 2021 |
| Journal | Sci Rep | Volume | 11 |
| Issue | 1 | Pages | 21059 |
| PubMed ID | 34702942 | Mgi Jnum | J:313673 |
| Mgi Id | MGI:6788122 | Doi | 10.1038/s41598-021-99965-8 |
| Citation | Evrard MR, et al. (2021) Preventing adolescent synaptic pruning in mouse prelimbic cortex via local knockdown of alpha4betadelta GABAA receptors increases anxiety response in adulthood. Sci Rep 11(1):21059 |
| abstractText | Anxiety is increasingly reported, especially in adolescent females. The etiology is largely unknown, which limits effective treatment. Layer 5 prelimbic cortex (L5PL) increases anxiety responses but undergoes adolescent synaptic pruning, raising the question of the impact of pruning on anxiety. Here we show that preventing L5PL pruning increases anxiety in response to an aversive event in adolescent and adult female mice. Spine density of Golgi-stained neurons decreased ~ 63% from puberty (~ PND35, vaginal opening) to post-puberty (PND56, P < 0.0001). Expression of alpha4betadelta GABAA receptors (GABARs) transiently increased tenfold in L5PL at puberty (P < 0.00001), but decreased post-pubertally. Both global and local knockdown of these receptors during puberty prevented pruning, increasing spine density post-pubertally (P < 0.0001), an effect reversed by blocking NMDA receptors (NMDARs). Pubertal expression of the NMDAR-dependent spine protein kalirin7 decreased (50%, P < 0.0001), an effect prevented by alpha4 knock-out, suggesting that alpha4betadelta-induced reductions in kalirin7 underlie pruning. Increased spine density due to local alpha4 knockdown at puberty decreased open arm time on the elevated plus maze post-pubertally (62%, P < 0.0001) in response to an aversive stimulus, suggesting that increases in L5PL synapses increase anxiety responses. These findings suggest that prelimbic synaptic pruning is necessary to limit anxiety in adulthood and may suggest novel therapies. |
