Larry Zweifel, PhD
Personal Statement
The main focus of my research efforts are to define how specific genes influence neuronal connectivity and function within neural circuits that regulate innate and motivated behaviors with a special emphasis on genes linked to psychiatric disorders such as schizophrenia and depression.
My laboratory utilizes conventional mouse genetics approaches coupled to viral-based strategies for projection specific gene manipulation, optogenetic and pharmacogenetic approaches, in vivo single unit electrophysiology recordings, whole-cell patch clamp, in vivo fiber-optic imaging, and behavior. We have recently demonstrated that a disease-related mutation in the human KCNN3 gene that encodes the calcium activated potassium channel SK3 significantly alters activity pattern regulation of midbrain dopamine neurons resulting in disruption of specific behavioral domains relevant to schizophrenia.
We have also shown that phasic activation of dopamine neurons potently influences fear processing by the amygdala and is critical for the prevention of generalized fear and anxiety. Other recent developments in the lab include the identification of CRF neurons in the central amygdala as key regulators of cued fear memory acquisition and the identification of a novel dopaminergic pathway within the hypothalamus that regulates social behavior.
Education
Ph.D. Neuroscience 2005, John Hopkins University
B.S. Biochemistry 1997, University of Missouri
Department Affiliations
Centers/Programs
Recent Publications
(2026 May 13)
Mol Psychiatry
Kielhold ML, Jacobs DS, Torrado Pacheco A, Lefner MJ, Bogachuk AP, Lebowitz JJ, Langdon AJ, Williams JT, Zweifel LS, Moghaddam B
(2026 May 6)
Nature
Godschall EN, Gungul TB, Sajonia IR, Buyukaksakal AK, Li O, Ogilvie S, Keeler AB, Tian G, Shi Y, Koita O, Guo CX, Deutsch TCJ, Steacy EJ, Crook M, Zhang Y, Conley NJ, Memi G, Webster AN, Yipkin Calhan O, Liu W, Akkoub A, Malik K, West KI, Michel-Le S, Karthikeyan A, van Gerven G, Dell'Aglio OA, Beier KT, Zweifel LS, Patel MK, Campbell JN, Deppmann CD, Güler AD
(2026 Mar 31)
bioRxiv
Villa AP, Trzeciak J, Wolfe D, Ehichioya DE, Falkenstein J, Wong JT, Dimalanta L, Kaiban W, Dhanoa J, Stevens G, Garcia F, Scarpa L, Chalfoun C, Zweifel LS, Awatramani R, Palmiter RD, Darvas M, Yamazaki S, Steele AD
(2026 Mar 14)
Nat Commun 17(1):
Cardozo Pinto DF, Guo MY, Pomrenze MB, Morishita W, Li MX, Zweifel LS, Eshel N, Malenka RC
(2026 Feb 12)
Neuron
Goode TD, Bernstein MX, Totty MS, Alipio JB, Vicidomini C, Pathak D, Besnard A, Chizari D, Sachdev N, Kritzer MD, Chung A, Duan X, Macosko E, Hicks SC, Zweifel LS, Sahay A
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