Ilana Witten

Ilana B. Witten is an American neuroscientist and professor of psychology and neuroscience at Princeton University. Witten studies the mesolimbic pathway, with a focus on the striatal neural circuit mechanisms driving reward learning and decision making.

Early life and education Witten grew up in Princeton, New Jersey, where her parents were both professors at Princeton University. Her father, Edward Witten, is a theoretical physicist and professor of mathematics at Princeton University, and her mother, Chiara Nappi is a professor of physics.

At Princeton, Witten majored in physics, but it was during her undergraduate degree that she became fascinated by biology, specifically neuroscience. Later in her undergraduate degree, Witten joined the lab of Michael J. Berry, where she conducted research towards her undergraduate thesis in computational neuroscience. Her undergraduate honors thesis was titled "Testing for Metabolic Efficiency in the Neural Code of the Retina" and was awarded by the Department of Physics. Under the mentorship of Eric Knudsen, Witten explored the neurobiological mechanisms of attention and strategies of information processing in the central nervous system of owls.

Sensory Information Processing in Barn Owls Prediction is a fundamental neural computation performed by the brain to mediate appropriate behavioral responses to changing and uncertain environments. In Witten's early graduate work, she explored how a specific neural circuit in the barn owl predicts the location of motion auditory stimuli. Using a Hebbian Plasticity model, Witten proposed that the synaptic plasticity underlying object detection and representation in the brain results from the difference in spatial representations of one type of input relative to that of another. In a first author paper in Science, published in 2010, Witten dissected the role of cholinergic neurons in the nucleus accumbens which, although they make up only 1% of the local neurons, play significant roles in modulating circuitry and driving behavior. They proposed to first use the technology to better understand reward behaviors and addiction in rodent models, and later to target specific neural circuits in the treatment of addiction disorders in humans through the administration of opsin encoding polynucleotides into the striatum. With these novel driver lines, Witten injected viruses to express Cre-dependent opsins in the rat brain to clarify the causal relationship between dopamine neuron firing and positive reinforcement in her novel rate driver lines.

Career and research Following postdoctoral work in the Deisseroth Lab, Witten was recruited to Princeton University in 2012 to become an assistant professor of psychology and neuroscience within the Princeton Neuroscience Institute and Department of Psychology.

In addition to her role as a principal investigator, Witten is a member of the committee for PNI graduate student admissions, a member of committee to select URMs for PNI summer program, a member of the committee for redesigning the graduate student curriculum, as well as many other committee roles to support her Princeton neuroscience community.

Dissecting Reward Circuitry In 2016, Witten and her team at Princeton published a paper looking at the distinct functions of different populations of midbrain dopamine neurons defined by their striatal target region. They found that dopamine neurons that project to the ventral striatum have stronger responses to reward consumption and reward predicting cues where as the dopamine neurons that project to the dorsomedial striatum respond robustly to contralateral choices. Witten and her team found that activity of cholinergic neurons regulates extinction learned cocaine-context associations. Interestingly, activation of the PL-NAc projection lead to decreased social preference, so Witten and her team sought to understand what information this projection was conveying. Though these neurons are canonically associated with reward circuitry, they have been implicated in various other behavioral variables, so Witten was interested in looking at their ability to encode reward, reward predicting cues, reward history, spatial position, kinematics, and behavioral choice. 2017-2022 NYSCF-Robertson Neuroscience Investigator Award 2017-2022 Simons Collaboration on the Global Brain Investigator 2017-2022 Co-PI on BRAIN Initiative U19 2015-2019 NIH R01 (from NIMH) 2015 PNI Innovation Award 2014-2016 McKnight Scholars Award in Neuroscience 2014-2017 Co-PI on BRAIN Initiative U01 2014 Award from Essig and Enright '82 Innovation Fund 2013-2017 Pew Scholarship in the Biomedical Sciences 2013 Winter Conference Brain Research Travel Award 2012-2017 NIH Director's New Innovator Award 2009-2012 Helen Hay Whitney Foundation Postdoctoral Fellowship 2008 Swartz Travel Fellowship for CoSyNe 2008 2003-2006 NSF Graduate Research Fellowship 2002 Allen G. Shenstone Prize in physics 2002 High honors awarded by the Princeton Department of Physics 2002 Sigma Xi Research Honor Society nomination 2000 Lucent Technology Prize of the Princeton Department of Physics 1998 Edward J. Bloustein Scholarship

Select publications

Combined social and spatial coding in a descending projection from prefrontal cortex. Murugan M, Park M, Jang HJ, Miller E, Taliaferro J, Cox J, Parker NF, Bhave V, Nectow A, Pillow J, Witten IB. Cell. Dec 2017. Dissociated sequential activity and stimulus encoding in striatal neurons during spatial working memory. Akhlaghpour H, Wiskerke J, Choi JY, Taliaferro J, Au J, Witten IB. eLife. 2016; 10.7554/eLife.19507. Linking cholinergic interneurons, synaptic plasticity, and behavior during the extinction of a cocaine-context association. Lee J, Finkelstein J, Choi JY, Witten IB. Neuron. 2016 May 18. Reward and choice encoding in terminals of midbrain dopamine neurons depends on striatal target. Parker NF, Cameron C, Taliaferro J, Choi JY, Lee J, Davidson T, Daw ND, Witten IB. Nature Neuroscience. 2016 Apr 25. doi:10.1038/nn.4287. Mesolimbic dopamine dynamically tracks, and is causally linked to, discrete aspects of value-based decision making. Saddoris MP, Sugam JA, Stuber GD, Witten IB, Deisseroth K, Carelli RM. Biol Psychiatry. 2015 May 15;77(10):903-11. doi: 10.1016/j.biopsych.2014.10.024. Epub 2014 Nov 13. Optical suppression of drug-evoked phasic dopamine release. McCutcheon JE, Cone JJ, Sinon CG, Fortin SM, Kantak PA, Witten IB, Deisseroth K, Stuber GD, Roitman MF. Front Neural Circuits. 2014 Sep 17;8:114. doi: 10.3389/fncir.2014.00114. eCollection 2014. Recombinase-driver rat lines: tools, techniques, and optogenetic application to dopamine-mediated reinforcement. Witten IB*, Steinberg E*, Lee SY, DavidsoTJ, Zalocusky KA, Brodsky M, Yizhar O, Cho SL, Gong S, Ramakrishnan C, Stuber GD, Tye K, Janak P, Deisseroth K. Neuron. 2011 Dec 8;72(5):721-33. Cholinergic interneurons control local circuit activity and cocaine conditioning. Witten IB*, Lin S*, Brodsky M*, Prakash R*, Diester I, Anikeeva P, Gradinaru V, Ramakrishnan C, Deisseroth K. Science. 2010. 330(6011):1677-81. A dominance hierarchy of auditory spatial cues in barn owls. Witten IB, Knudsen PF, Knudsen EI. PLoS ONE. 2010; 5(4): e10396. A Hebbian learning rule mediates asymmetric plasticity in aligning sensory representations. Witten IB, Knudsen EI, Sompolinsky H. Journal of Neurophysiology. 2008; 100(2): 1067–79. Dynamic shifts in the owl's auditory space map predict moving sound location. Witten IB*, Bergan JF*, Knudsen EI. Nature Neuroscience. 2006; 9(11):1439- 45. Why seeing is believing: merging auditory and visual worlds. Witten IB, Knudsen EI. Neuron. 2005; 48(3):489-96.