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 pharmacogentic 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. Biochemisty 1997, University of Missouri

Department Affiliations

Recent Publications

An endogenous opioid circuit determines state-dependent reward consumption.
(2021 Oct 13)
Nature
Castro DC, Oswell CS, Zhang ET, Pedersen CE, Piantadosi SC, Rossi MA, Hunker AC, Guglin A, Morón JA, Zweifel LS, Stuber GD, Bruchas MR

'Fearful-place' coding in the amygdala-hippocampal network.
(2021 Sep 17)
Elife 10():
Kong MS, Kim EJ, Park S, Zweifel LS, Huh Y, Cho J, Kim JJ

A midbrain dynorphin circuit promotes threat generalization.
(2021 Oct 11)
Curr Biol 31(19): 4388-4396.e5
Fellinger L, Jo YS, Hunker AC, Soden ME, Elum J, Juarez B, Zweifel LS

Intercalated amygdala clusters orchestrate a switch in fear state.
(2021 Jun)
Nature 594(7863): 403-407
Hagihara KM, Bukalo O, Zeller M, Aksoy-Aksel A, Karalis N, Limoges A, Rigg T, Campbell T, Mendez A, Weinholtz C, Mahn M, Zweifel LS, Palmiter RD, Ehrlich I, Lüthi A, Holmes A

Central amygdala circuits in valence and salience processing.
(2021 Jul 23)
Behav Brain Res 410(): 113355
Kong MS, Zweifel LS

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