The goal of my research is to identify new molecular mechanisms in neuronal types in regulating resilience, depression and cognition, and to elucidate the mechanisms of action of slow-acting and fast-acting antidepressants. I use cell type specific molecular tools to identify molecules, cell types, neuronal functions, and signaling pathways in rodent models. I implement behavioral paradigms and use cell-type specific molecular tools, chemogenetics, and in vivo photometry in transgenic mice to identify the roles of new molecules in specific cell types in learning and in inducing resilience to stress. Thus far, my studies elucidated novel roles for inhibitory interneuron populations in the ventral dentate gyrus in mediating anhedonia, susceptibility and resilience to stress, and cognition.
Umschweif G, Medrihan L, Guillén-Samander A, Wang, W, Sagi Y, Greengard P (2021). Identification of Neurensin-2 as a novel modulator of emotional behavior, Mol. Psy. (Epub. DOI 10.1038/s41380-021-01058-5).
Umschweif G, Medrihan L, McCabe KA, Sagi Y, Greengard P (2021). Activation of the p11/SMARCA3/Neurensin-2 pathway in parvalbumin interneurons mediates the response to chronic antidepressants, Mol. Psy. (Epub. DOI 10.1038/s41380-021-01059-4).
Medrihan L, Umschweif G, Sinha A, Reed S, Gindinova K, Sinha SC, Greengard P, Sagi Y (2020). Reduced Kv3.1 activity in dentate gyrus parvalbumin cells induces vulnerability to depression. Biol. Psy. 88(5):405-414.
Hur JY, Frost GR, Wu X, Crump C, Pan SJ, Wong E, Barros M, Li T, Nie P, Zhai Y, Wang J, Chyong J, Guo L, McKenzie A, Ming C, Zhou X, Wang M, Sagi Y, Renton A, Esposito B, Kim Y, Sadleir KR, Trinh I, Rissman R, Vassar R, Zhang B, Johnson D, Masliah E, Greengard P, Goate A, Li Y (2020). Innate immunity protein IFITM3 modulates γ-secretase in Alzheimer disease. Nature 586(7831):735-740.
Umschweif G, Greengard P, Sagi Y (2021). The dentate gyrus in depression. Eur J. Neurosc. 53(1):39-64.
Sagi Y, Medrihan L, George K, Barney M, McCabe KA, Greengard P (2020). Emergence of 5-HT5A signaling in parvalbumin neurons mediates delayed antidepressant action. Mol. Psy. 25(6):1191-1201.
Medrihan L, Sagi Y, Inde Z, Krupa O, Daniels C, Peyrache A, Greengard P (2017). Initiation of behavioral response to antidepressants by cholecystokinin neurons of the dentate gyrus. Neuron 95(3): 564-576