Academic Appointments


Honors & Awards


  • Firmenich Next Generation Chair in Neuroscience, Stanford University (2017)
  • David Huntington Dean's Faculty Scholars, Stanford University (2015)
  • Scholar Award, Ajinomoto Innovation Alliance Program (2014)
  • Terman Scholar, Stanford University (2014)
  • Scholar Award, Whitehall Foundation (2013)

Current Research and Scholarly Interests


Our goal is to understand how brain circuits mediate motivated behaviors, and how maladaptive changes in these circuits cause mood disorders. To achieve this goal, we focus on studying the neural circuits for pain and addiction, as both trigger highly motivated behaviors, whereas, transitioning from acute to chronic pain or from recreational to compulsive drug use involves maladaptive changes of the underlying neuronal circuitry.

2018-19 Courses


Stanford Advisees


Graduate and Fellowship Programs


All Publications


  • Dynamic salience processing in paraventricular thalamus gates associative learning. Science (New York, N.Y.) Zhu, Y., Nachtrab, G., Keyes, P. C., Allen, W. E., Luo, L., Chen, X. 2018; 362 (6413): 423–29

    Abstract

    The salience of behaviorally relevant stimuli is dynamic and influenced by internal state and external environment. Monitoring such changes is critical for effective learning and flexible behavior, but the neuronal substrate for tracking the dynamics of stimulus salience is obscure. We found that neurons in the paraventricular thalamus (PVT) are robustly activated by a variety of behaviorally relevant events, including novel ("unfamiliar") stimuli, reinforcing stimuli and their predicting cues, as well as omission of the expected reward. PVT responses are scaled with stimulus intensity and modulated by changes in homeostatic state or behavioral context. Inhibition of the PVT responses suppresses appetitive or aversive associative learning and reward extinction. Our findings demonstrate that the PVT gates associative learning by providing a dynamic representation of stimulus salience.

    View details for PubMedID 30361366

  • The coding of cutaneous temperature in the spinal cord. Nature neuroscience Ran, C., Hoon, M. A., Chen, X. 2016; 19 (9): 1201-1209

    Abstract

    The spinal cord is the initial stage that integrates temperature information from peripheral inputs. Here we used molecular genetics and in vivo calcium imaging to investigate the coding of cutaneous temperature in the spinal cord in mice. We found that heating or cooling the skin evoked robust calcium responses in spinal neurons, and their activation threshold temperatures distributed smoothly over the entire range of stimulation temperatures. Once activated, heat-responding neurons encoded the absolute skin temperature without adaptation and received major inputs from transient receptor potential (TRP) channel V1 (TRPV1)-positive dorsal root ganglion (DRG) neurons. By contrast, cold-responding neurons rapidly adapted to ambient temperature and selectively encoded temperature changes. These neurons received TRP channel M8 (TRPM8)-positive DRG inputs as well as novel TRPV1(+) DRG inputs that were selectively activated by intense cooling. Our results provide a comprehensive examination of the temperature representation in the spinal cord and reveal fundamental differences in the coding of heat and cold.

    View details for DOI 10.1038/nn.4350

    View details for PubMedID 27455110

  • A thalamic input to the nucleus accumbens mediates opiate dependence NATURE Zhu, Y., Wienecke, C. F., Nachtrab, G., Chen, X. 2016; 530 (7589): 219-?

    Abstract

    Chronic opiate use induces opiate dependence, which is characterized by extremely unpleasant physical and emotional feelings after drug use is terminated. Both the rewarding effects of a drug and the desire to avoid withdrawal symptoms motivate continued drug use, and the nucleus accumbens is important for orchestrating both processes. While multiple inputs to the nucleus accumbens regulate reward, little is known about the nucleus accumbens circuitry underlying withdrawal. Here we identify the paraventricular nucleus of the thalamus as a prominent input to the nucleus accumbens mediating the expression of opiate-withdrawal-induced physical signs and aversive memory. Activity in the paraventricular nucleus of the thalamus to nucleus accumbens pathway is necessary and sufficient to mediate behavioural aversion. Selectively silencing this pathway abolishes aversive symptoms in two different mouse models of opiate withdrawal. Chronic morphine exposure selectively potentiates excitatory transmission between the paraventricular nucleus of the thalamus and D2-receptor-expressing medium spiny neurons via synaptic insertion of GluA2-lacking AMPA receptors. Notably, in vivo optogenetic depotentiation restores normal transmission at these synapses and robustly suppresses morphine withdrawal symptoms. This links morphine-evoked pathway- and cell-type-specific plasticity in the paraventricular nucleus of the thalamus to nucleus accumbens circuit to opiate dependence, and suggests that reprogramming this circuit holds promise for treating opiate addiction.

    View details for DOI 10.1038/nature16954

    View details for Web of Science ID 000369916700039

    View details for PubMedID 26840481

    View details for PubMedCentralID PMC4814115