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

Presynaptic sensor and silencer of peptidergic transmission reveal neuropeptides as primary transmitters in pontine fear circuit.
(2024 Jul 17)
Cell
Kim DI, Park S, Park S, Ye M, Chen JY, Kang SJ, Jhang J, Hunker AC, Zweifel LS, Caron KM, Vaughan JM, Saghatelian A, Palmiter RD, Han S

CRF release from a unique subpopulation of accumbal neurons constrains action-outcome acquisition in reward learning.
(2024 Jul 7)
bioRxiv
Eckenwiler EA, Ingebretson AE, Stolley JJ, Fusaro MA, Romportl AM, Ross JM, Petersen CL, Kale EM, Clark MS, Schattauer SS, Zweifel LS, Lemos JC

Valence and Salience Encoding in the Central Amygdala.
(2024 Jul 7)
bioRxiv
Kong MS, Ancell E, Witten DM, Zweifel LS

Estradiol elicits distinct firing patterns in arcuate nucleus kisspeptin neurons of females through altering ion channel conductances.
(2024 Jun 12)
bioRxiv
Qiu J, Voliotis M, Bosch MA, Li XF, Zweifel LS, Tsaneva-Atanasova K, O'Byrne KT, Rønnekleiv OK, Kelly MJ

Opto-seq reveals input-specific immediate-early gene induction in ventral tegmental area cell types.
(2024 Jun 12)
Neuron
Simon RC, Loveless MC, Yee JX, Goh B, Cho SG, Nasir Z, Hashikawa K, Stuber GD, Zweifel LS, Soden ME

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