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Neuroscience Graduate Program at UCSF

Faculty - Mazen Kheirbek, Ph.D.

Neural circuits underlying emotional behaviors


Research Description

Our primary goal is to delineate the neuronal circuits that underlie emotional behavior. In particular, we are interested in those circuits that are disrupted in mood and anxiety-related disorders. Our main focus is the hippocampus, which, in addition to its role in learning and memory, has become increasingly implicated in the pathophysiology of anxiety disorders. We take an integrative approach; applying novel technologies to both monitor and control genetically identified neural networks in real time. For example, we recently used optogenetic techniques to dissect the functional heterogeneity of the hippocampus along its dorsoventral axis.  We showed that the dorsal pole plays important roles in exploratory behavior and contextual processing, while the ventral pole drives anxiety-related behavior.

Our current efforts are focused on dissecting the mechanisms by which distributed neural circuits generate affective behaviors.  In one line of research, we are focused on understanding the role of the ventral hippocampus in behavior. Specifically, we are mapping the neuronal subtypes, projection streams and the subcortical targets of the ventral hippocampus to determine how this network controls fear and anxiety-related behavior. In a complementary line of research, we are investigating how the dentate gyrus subfield of the hippocampus processes information about contexts with varying emotional valences  - for instance, how is a fear-inducing context encoded differently than a safe one? Here, we are especially interested in the role of adult hippocampal neurogenesis--the incorporation of new neurons in the adult dentate gyrus--plays in the encoding and retrieval of fear memories. To address these questions, our group employs a variety of in vivo techniques. Currently, we use cell-type specific Ca2+ imaging (both miniaturized microscopes and 2-photon imaging), behavioral, electrophysiological, and optogenetic techniques.

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Current Projects

1. How does the hippocampus modulate subcortical circuits to control anxiety-related behavior?

2. What is the functional relevance of adult neurogenesis in the dentate gyrus to behavior and local circuit function?

3. How does the ventral hippocampus encode innately aversive environments?

4. How are emotionally salient stimuli represented in the hippocampus, and how does emotional state modulate hippocampal function?

5. How does the early-life development of limbic circuits impact adult emotional behavior?

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Lab Members

Jeremy Biane, PhD, Postdoc

Alexander Goldberg, Research Technician

Jessica Jimenez, MD, PhD Student

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Selected Publications

Full list: http://www.ncbi.nlm.nih.gov/pubmed/?term=kheirbek+ma

Danielson NB, Kaifosh P, Zaremba JD, Lovett-Barron M, Tsai J, Denny CA Balough EM, Goldberg AR, Drew DJ, Hen R, Losonczy A, Kheirbek MA (2016) Distinct contribution of adult-born hippocampal granule cells to context encoding Neuron. 90(1): 101-112 

Kheirbek MA, Drew LJ, Costantini DO, Burghardt N, Tannenholz L, Ahmari SE, Zeng H, Fenton AA, Hen R (2013) Differential control of learning and anxiety along the dorso-ventral axis of the dentate gyrus, Neuron, 77: 955-968

Kheirbek MA, Klemenhagen KK, Sahay A, Hen R (2012) Neurogenesis and generalization: a new approach to stratify and treat anxiety disorder. Nature Neuroscience 2012 Dec;15(12):1613-20.

Kheirbek MA, Tannenholz, L. & Hen, R. (2012) NR2B-Dependent Plasticity of Adult-Born Granule Cells is Necessary for Context Discrimination. Journal of Neuroscience, 32, 8696-8702.

Lovett-Barron M*, Kaifosh P*, Kheirbek MA, Danielson N, Zaremba JD, Reardon TR, Turi GF, Hen R, Zemelman BV, Losonczy A. (2014) Dendritic inhibition in the hippocampus supports fear learning. Science 343. (857-63) (*equal contribution)10.

Ahmari SE, Spellman T, Douglass N, Kheirbek MA, Deisseroth K, Gordon JA, Hen R (2013) Repeated corticostriatal stimulation generates persistent OCD-like behavior. Science, 340, 1234-1239

Denny CA, Kheirbek MA, Alba EL, Tanaka, KF, Brachman RA, Laughman KB, Tomm NK, Turi GF, Losonczy A & Hen R (2014) Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis. Neuron, 83, 189-201.

Drew LJ, Kheirbek MA, Luna VM, Denny CA, Cloidt MA, Wu MV, Jain S, Scharfman HE, Hen R. (2015) Activation of local inhibitory circuits in the dentate gyrus by adult-born neurons. Hippocampus, 2015 Dec 14. doi: 10.1002/hipo.22557. [Epub ahead of print]

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Mazen Kheirbek, Ph.D.



Email

mazen.kheirbek@ucsf.edu

Phone 415-514-8326

Office Address

675 Nelson Rising Lane
Box 0444, room 514D
San Francisco, CA 94158

Other Websites

Lab