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

Endocannabinoids facilitate transitory reward engagement through retrograde gain-control.
(2025 Jan 8)
bioRxiv
Marcus DJ, English AE, Chun G, Seth EF, Oomen R, Hwang S, Wells B, Piantadosi SC, Suko A, Li Y, Zweifel LS, Land BB, Stella N, Bruchas MR

Valence and salience encoding in the central amygdala.
(2025 Jan 10)
Elife 13():
Kong MS, Ancell E, Witten DM, Zweifel LS

Dopamine D2 receptors in the bed nucleus of the stria terminalis modulate alcohol-related behaviors.
(2024 Jun)
Addict Neurosci 11():
Pati D, Taxier LR, Xia M, Lee SI, Conley SY, Sides T, Boyt KM, Hunker AC, Zweifel LS, Kash TL

Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.
(2024 Dec 13)
Elife 13():
Qiu J, Voliotis M, Bosch MA, Li XF, Zweifel LS, Tsaneva-Atanasova K, O'Byrne KT, Rønnekleiv OK, Kelly MJ

Reductions of Grin2a in adolescent dopamine neurons confers aberrant salience and related psychosis phenotype.
(2024 Oct 28)
bioRxiv
Kielhold ML, Jacobs DS, Torrado-Pacheco A, Lebowitz JJ, Langdon AJ, Williams JT, Zweifel LS, Moghaddam B

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