Mazen Kheirbek, PhD

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Overview

Academic Appointments

  • Assistant Professor of Clinical Neurobiology in Psychiatry

Research

Our primary interest is dissecting the neuronal circuits that underlie emotional and motivational behavior. To accomplish this, we take an integrative approach, combining genetic, behavioral, electrophysiological and optical techniques to probe and manipulate these circuits in mouse models.

Our research group is focused on understanding the neuronal circuits that underlie emotional behavior, so that we may understand how they go awry in certain anxiety disorders. For this, we have focused on the hippocampus (HPC), which, in addition to its role in learning and memory, has become increasingly implicated in the pathophysiology of anxiety disorders. Recently, using optogenetic techniques, we have shown that the HPC is functionally heterogeneous along its dorsoventral axis, with the dorsal pole playing a role in exploratory behavior and contextual processing and the ventral pole driving anxiety like behaviors. Our current efforts are focused on dissecting the projections of the HPC to limbic regions (amygdala and hypothalamus) in the control of emotional behavior. We compliment these efforts with freely moving, cell-type specific functional imaging techniques to determine a neuronal signature for fear and anxiety within hippocampal circuits. In addition, we are investigating how the hippocampus encodes experiences that have differing emotional valence (for example fearful vs safe or appetitive vs aversive).

In brief, our research is focused on: 1. Functional mapping of the input-output circuitry of the hippocampus in the control of emotional behavior; 2. How emotionally salient information is represented in the hippocampus, and how emotional state (such as increased anxiety) modulates hippocampal function; 3. How early-life development of hippocampal circuitry impacts adult emotional behavior; 4. Determining novel signatures for fear and anxiety within population activity in the hippocampus.

For this we use behavioral, genetic and electrophysiological techniques, cell-type specific functional calcium imaging (freely moving miniaturized microscopes and 2-photon in vivo imaging), and optogenetic/chemogenetic perturbations to probe these circuits that underlie emotional behavior.

Grants

THE ROLE OF NEUROGENESIS IN HIPPOCAMPAL EXCITABILITY AND THE ANTIDEPRESSANT RESPONSE (Private)

Jul 15 2011 - Jul 14 2014

MODULATING PLASTICITY IN ADULT-BORN NEURONS OF THE DENTATE G YRUS (Federal Gov)

Jul 1 2011 - Oct 31 2012

Selected Publications

  • Kheirbek MA, Drew LJ, Costantini DO, Burghardt N, Tannenholz L, Ahmari SE, Zeng H, Fenton AA, Hen R : Differential control of learning and anxiety along the dorso-ventral axis of the dentate gyrus. Neuron 2013;77: 955-968
  • Kheirbek MA, Klemenhagen KK, Sahay A, Hen R : Neurogenesis and generalization: a new approach to stratify and treat anxiety disorder. Nature Neuroscience 2012;15: 1613-20
  • Kheirbek MA, Tannenholz, L. & Hen, R. : NR2B-Dependent Plasticity of Adult-Born Granule Cells is Necessary for Context Discrimination.. Journal of Neuroscience 2012;32: 8696-8702
  • Lovett-Barron M*, Kaifosh P*, Kheirbek MA, Danielson N, Zaremba JD, Reardon TR, Turi GF, Hen R, Zemelman BV, Losonczy A. : Dendritic inhibition in the hippocampus supports fear learning.. Science 2014;343: 857-63
  • Denny CA, Kheirbek MA, Alba EL, Tanaka, KF, Brachman RA, Laughman KB, Tomm NK, Turi GF, Losonczy A & Hen R: Hippocampal memory traces are differentially modulated by experience, time, and adult neurogenesis.. Neuron 83;83: 189-201