| First Author | Ulloa Severino FP | Year | 2023 |
| Journal | Nat Commun | Volume | 14 |
| Issue | 1 | Pages | 5522 |
| PubMed ID | 37684234 | Mgi Jnum | J:340552 |
| Mgi Id | MGI:7527860 | Doi | 10.1038/s41467-023-41078-z |
| Citation | Ulloa Severino FP, et al. (2023) Training-induced circuit-specific excitatory synaptogenesis in mice is required for effort control. Nat Commun 14(1):5522 |
| abstractText | Synaptogenesis is essential for circuit development; however, it is unknown whether it is critical for the establishment and performance of goal-directed voluntary behaviors. Here, we show that operant conditioning via lever-press for food reward training in mice induces excitatory synapse formation onto a subset of anterior cingulate cortex neurons projecting to the dorsomedial striatum (ACC(-->DMS)). Training-induced synaptogenesis is controlled by the Gabapentin/Thrombospondin receptor alpha2delta-1, which is an essential neuronal protein for proper intracortical excitatory synaptogenesis. Using germline and conditional knockout mice, we found that deletion of alpha2delta-1 in the adult ACC(-->DMS) circuit diminishes training-induced excitatory synaptogenesis. Surprisingly, this manipulation does not impact learning but results in a significant increase in effort exertion without affecting sensitivity to reward value or changing contingencies. Bidirectional optogenetic manipulation of ACC(-->DMS) neurons rescues or phenocopies the behaviors of the alpha2delta-1 cKO mice, highlighting the importance of synaptogenesis within this cortico-striatal circuit in regulating effort exertion. |
