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

Recent Publications

A population of dopaminergic neurons in the substantia nigra is required for food-anticipatory activity.
(2026 Sep 17)
Curr Biol
Villa AP, Trzeciak J, Wolfe D, Ehichioya DE, Falkenstein J, Wong JT, Wu R, Dimalanta L, Kaiban W, Dhanoa J, Stevens G, Shah M, Garcia F, Scarpa L, Chalfoun C, Zweifel LS, Awatramani R, Palmiter RD, Darvas M, Yamazaki S, Steele AD

Author Correction: Endocannabinoids facilitate reward engagement through retrograde gain control.
(2026 Sep)
Nature 657(8132): E18
Marcus DJ, English AE, Chun G, Seth EF, Oommen R, Hwang S, Wells BA, Piantadosi SC, Suko A, Kenmochi SJ, Parasnis AA, Ancell E, Li Y, Zweifel LS, Land BB, Stella N, Bruchas MR

Endocannabinoids facilitate reward engagement through retrograde gain control.
(2026 Aug 26)
Nature
Marcus DJ, English AE, Chun G, Seth EF, Oommen R, Hwang S, Wells BA, Piantadosi SC, Suko A, Kenmochi SJ, Parasnis AA, Ancell E, Li Y, Zweifel LS, Land BB, Stella N, Bruchas MR

Esr1-dependent signaling and transcriptional maturation in the medial preoptic area of the hypothalamus shape the development of mating behavior during adolescence.
(2026 Jun 19)
Elife 14():
Hashikawa K, Hashikawa Y, Briones B, Ishii KK, Liu Y, Rossi M, Basiri ML, Chen JY, Ahmad O, Mukundan R, Johnston N, Simon R, Soetedjo J, Siputro J, McHenry J, Palmiter RD, Rubinow D, Zweifel LS, Stuber GD

Grin2a knockout in adolescent dopamine neurons disrupts prediction error signaling and produces a phenotype relevant to schizophrenia.
(2026 Sep)
Mol Psychiatry 31(9): 5474-5485
Kielhold ML, Jacobs DS, Torrado Pacheco A, Lefner MJ, Bogachuk AP, Lebowitz JJ, Langdon AJ, Williams JT, Zweifel LS, Moghaddam B

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