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Melissa Warden

Assistant Professor and Miriam M. Salpeter Fellow

Educational Background

  • A.B., Princeton University
  • Ph.D., Massachusetts Institute of Technology
  • Postdoctoral Fellow, Stanford University

Website(s)

Overview

Melissa Warden is an Assistant Professor and Miriam M. Salpeter Fellow in the Department of Neurobiology and Behavior at Cornell University, and is a member of the Cornell Neurotech Advisory Group and the Biomedical Engineering and Psychology graduate fields. She received an A.B. in Molecular Biology from Princeton University and a Ph.D. in Systems Neuroscience from the Massachusetts Institute of Technology, where she investigated prefrontal neuronal encoding of multi-item short-term memory with Earl K. Miller. As a postdoctoral fellow with Karl Deisseroth at Stanford University she studied cortical control of neuromodulatory systems in motivated behavior. Her research at Cornell integrates imaging, neurophysiological, and cellular and molecular approaches to study the neural circuits mediating reward and motivated behavior and their dysfunction. She has received a number of awards including the NIH Director’s New Innovator Award, a Robertson Neuroscience Investigator Award from the New York Stem Cell Foundation, a NARSAD Young Investigator Award from the Brain and Behavior Research Foundation, a Sloan Research Fellowship from the Alfred P. Sloan Research Foundation, and a Research Grant from the Whitehall Foundation.

Research

Our lab seeks to understand the neural circuitry underlying complex cognition and behavior, with a focus on systems mediating reward and motivation.  We are interested in both the normal function of these circuits and how they become dysfunctional in depression.  We study these systems with an observational and causal approach, combining monitoring and decoding of neural activity with control of defined circuit elements.  Our primary current research goals are to determine how neural signals reflecting reward and motivation are constructed and used to control affective state and behavior.

Many of our research projects are focused on the serotonergic dorsal raphe nucleus (DRN) and the dopaminergic ventral tegmental area (VTA). These small, ancient brainstem systems send projections widely throughout the brain and are in a prime position to globally influence behavioral state.  Neurons in these regions encode quantities including reward prediction error, expected reward, the presence of acute stressors, and arousal.  What kind of information is transmitted to these regions, and how is this information used to construct these quantities?  How do these regions influence downstream neural signaling?  What behavioral and cognitive consequences result from changes in afferent and efferent information flow?

We investigate these fundamental questions by perturbing selected circuits and observing the effects on both neural activity and behavior.  Using this approach we hope to shed light on both the normal function of these systems and how dysfunction in information flow contributes to disease states such as depression.  In pursuit of these goals, the lab employs a multidisciplinary approach combining optogenetics, imaging, high-density freely moving neurophysiology, patch clamp electrophysiology, behavior, and computation.

Keywords

motivated behavior, reward, decisions, neural circuits, neuromodulators, prefrontal cortex, optogenetics, imaging, neurophysiology

Courses

Departments/Programs

  • Neurobiology and Behavior

Graduate Fields

  • Neurobiology and Behavior
  • Biomedical Engineering
  • Psychology

Affiliations

  • Cornell Neurotech

Publications

  • Lundqvist M, Herman P, Warden MR, Brincat SL, Miller EK. Gamma and beta bursts during working memory readout suggest roles in its volitional control. bioRxiv. 2017 122598; doi: https://doi.org/10.1101/122598.

  • Ferenczi EA, Zalocusky KA, Liston C, Grosenick L, Warden MR, Amatya D, Katovich K, Mehta H, Patenaude B, Ramakrishnan C, Kalanithi P, Etkin A, Knutson B, Glover GH, Deisseroth K. Prefrontal cortical regulation of brainwide circuit dynamics and reward-related behavior. Science. 2016 Jan 1;351(6268):aac9698.

  • Sidor MM, Spencer SM, Dzirasa K, Parekh PK, Tye KM, Warden MR, Arey RN, Enwright JF 3rd, Jacobsen JP, Kumar S, Remillard EM, Caron MG, Deisseroth K, McClung, CA. Daytime spikes in dopaminergic activity drive rapid moodcycling in mice. Mol Psychiatry. 2015 Nov;20(11):1406-19.

  • Guru A, Post RJ, Ho YY, Warden MR. Making sense of optogenetics. Int J Neuropsychoph. 2015 Jul 25:1-8.

  • Sidor MM, Davidson TJ, Tye KM, Warden MR, Deisseroth K, McClung CA. In vivo optogenetic stimulation of the rodent central nervous system. J Vis Exp. 2015 Jan 15;95:e51483.

  • Warden MR, Cardin JA, Deisseroth K. Optical Neural Interfaces. Annu Rev Biomed Eng. 2014 Jul 11;16:103-129.

  • Lammel S, Tye KM, Warden MR. Progress in understanding mood disorders: optogenetic dissection of neural circuits. Genes Brain Behav. 2014 Jan;13(1):38-51.

  • Rigotti M, Barak O, Warden MR, Wang XJ, Daw N, Miller EK, Fusi S. The importance of mixed selectivity in complex cognitive tasks. Nature. 2013 May 30;497(7451):585-590.

  • Kim SY*, Adhikari A*, Lee SY, Marshel JH, Kim CK, Mallory CS, Lo M, Pak S, Mattis J, Lim BK, Malenka RC, Warden MR, Neve R, Tye KM, Deisseroth K. Diverging neural pathways assemble a behavioral state from separable features in anxiety. Nature. 2013 Apr 11;496(7444):219-223.

  • Tye KM*, Mirzabekov JJ*, Warden MR*, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K. Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Nature. 2013 Jan 24;493(7433):537-541.  *equal contribution

  • Warden MR, Selimbeyoglu A, Mirzabekov JJ, Lo M, Thompson KR, Kim SY, Adhikari A, Tye KM, Frank LM, Deisseroth K. A prefrontal cortex-brainstem neuronal projection that controls response to behavioural challenge. Nature. 2012 Dec 20;492(7429):428-432.

  • Anikeeva P*, Andalman AS*, Witten I, Warden M, Goshen I, Grosenick L, Gunaydin LA, Frank LM, Deisseroth K. Optetrode: a multichannel readout for optogenetic control in freely moving mice. Nat Neurosci. 2012 Jan;15(1):163-70.

  • Warden MR, Miller EK. Task-dependent changes in short-term memory in the prefrontal cortex. J Neurosci. 2010 Nov 24;30(47):15801-10.

  • Siegel M, Warden MR, Miller EK. Phase-dependent neuronal coding of objects in short-term memory. Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21341-6.

  • Warden MR, Miller EK. The representation of multiple objects in prefrontal neuronal delay activity. Cereb Cortex. 2007 Sep;17 Suppl 1:i41-50.