Directora de tesis: Chiu, ChiayuSanguinetti González, Nicole2025-04-092025-04-092025https://repositoriobibliotecas.uv.cl/handle/uvscl/15626GABAergic interneurons (INs) that co-express the neuropeptide somatostatin (SOM-INs) play an essential role in controlling cortical activity by forming inhibitory synapses on dendrites of pyramidal neurons (PNs). However, the mechanisms that regulate inhibition from SOM-INs are less understood. Given commonalities between SOM-INs and the endocannabinoid (eCB) system in influencing cognitive and emotional processing, we examine the possibility that GABAergic synapses from SOM-INs can be modulated by eCB signaling in the prefrontal cortex (PFC). Using optogenetic tools to selectively activate SOM-INs in whole-cell patch experiments, we found that postsynaptic inhibitory currents (IPSC) in layer II/III PNs evoked by photostimulation of SOM- INs (SOM-IPSCs) depressed following bath application of WIN 55,212-2, a potent agonist of cannabinoid type 1 receptors (CB1Rs). Supporting the role of CB1Rs in presynaptic neurotransmitter release, WIN depression from SOM-INs was accompanied by changes in paired- pulse ratio (PPR) and is absent in mice lacking CB1Rs specifically in SOM-INs (SOM-CB1R KOs). Importantly, a brief postsynaptic depolarization of the PNs induced suppression of inhibition transiently (DSI), an effect that was eliminated by the CB1R inverse agonist AM251. Moreover, theta-burst stimulation (TBS) triggered long-term depression from SOM-INs (iLTD) that was blocked by AM251 and was absent in SOM-CB1R KO animals. Consistent with a presynaptic expression of TBS-iLTD, we observed a decrease in PPR from SOM-IPSCs following plasticity induction. In addition, WIN and TBS have no effect on IPSCs mediated by photostimulating parvalbumin-expressing interneurons (PV-INs), suggesting that inhibition from PV-INs is not regulated by eCB signaling. Altogether, these results reveal an input-specific eCB modulation from SOM-INs, a major source of dendritic inhibition in the PFC, to potentially control information flow from multiple sources to shape associative cognitive processing.enReceptores de cannabinoidesDepresionTDOC