Hao Li

Hao Li, Ph.D.
Assistant Professor
Principal Investigator

Dept. of Psychiatry & Behavioral Sciences
Dept. of Neuroscience
Feinberg School of Medicine
Northwestern University
hali at salk.edu

Hao was born and raised in Beijing, China, and then moved to the U.S. after he earned a bachelor's degree from Shandong University. He completed his Ph.D. in neuroscience with Dr. Thomas Jhou at the Medical University of South Carolina, studying circuit mechanisms underlying punishment processing.

In 2019, Hao started his postdoctoral training with Dr. Kay Tye at the Salk Institute, focusing on how neurotensin guides valence assignment in the amygdala during associative learning.

In his spare time, Hao enjoys playing soccer, rock climbing, watching animes, and spending time with his cats.

Curriculum Vitae

  • Employment & Education
  • Assistant Professor
    Northwestern University (Starting in 2023)
    Postdoctoral Fellow
    Salk Institute for Biological Studies (2019 - Present)
    with Dr. Kay Tye
    Doctor of Philosophy
    Medical University of South Carolina (2014 - 2019)
    with Dr. Thomas Jhou
    Research Technician
    Emory University (2013 - 2014)
    with Dr. David Walker
    Master of Science
    University of South Dakota (2011 - 2013)
    with Dr. Kenneth Renner
    Bachelor of Science
    Shandong University (2007 - 2011)
  • Awards
  • 2022
    Warren Alpert Distinguished Scholar Fellowship (awarded but declined)
  • 2022
    NIDA Pathway to Independence Award K99/R00
  • 2021
    American College of Neuropsychopharmacology (ACNP) Travel Award
  • 2019
    Chinese Government Award For Outstanding Students Abroad
  • 2019
    Medical University of South Carolina Research Excellence Award
  • 2018
    Medical University of South Carolina Travel Fellowship
  • 2018
    Winter Conference on Brain Research Travel Fellow
  • 2017
    RIKEN Brain Science Institute Travel Award
  • 2012
    University of South Dakota Cable Graduate Travel Award
  • Invited Talks
  • 2022
    NIDA Behavioral Neuroscience Research Branch, MD, USA
  • 2022
    Icahn School of Medicine at Mount Sinai, NY, USA
  • 2022
    Northwestern University, IL, USA
  • 2022
    Rutgers University, NJ, USA
  • 2019
    Massachusetts Institute of Technology, MA, USA
  • 2019
    Harvard University, MA, USA
  • 2018
    University of Washington, WA, USA
  • 2018
    Stanford University, CA, USA
  • 2018
    Cold Spring Harbor Laboratory, NY, USA

Previous Work

Click on each section to view detailed project summary

Neuropeptidergic modulation on valence assignment (Postdoc)

During associative learning, distinct of basolateral amygdala (BLA) neurons are assigned with positive and negative valence. However, the specific mechanism underlying the assignment of valence to the appropriate BLA neurons remains unclear.

My postdoctoral project has uncovered a neurotensin (NT) role in mediating valance assignment in the BLA (Li et al., 2022, Nature). Specifically, I found that NT released from the paraventricular nucleus of the thalamus (PVT) mediates BLA ensemble formation of both positive and negative valences and bi-directionally modulates reward and punishment learning in a dose-dependent manner. One challenge was to isolate NT from co-released glutamate, as we had identified that NT inputs to the BLA co-release glutamate. Typical approaches such as optogenetics would inevitably affect glutamate along with neuropeptides and could potentially confound the interpretation of the results. To overcome this, I collaborated with Drs. Feng Zhang and Yulong Li’s labs on adapting CRISPR-mediated Nt gene knockout and validating a genetically-encoded NT sensor. As both approaches showed high specificity to NT, I found that the Nt gene knockout in the PVTNT-BLA projection promotes punishment learning, while PVTNT-BLA optogenetic activation promotes reward learning. Consistently, both calcium dynamics in PVTNT axon terminals and NT sensor dynamics in the BLA are enhanced after reward learning and diminished after punishment learning.

Using functional clustering, and computational analysis, I found that Nt gene knockout in the PVT-BLA blunts BLA encoding of learned valences at both the single-unit and population levels. Furthermore, CRISPR and control groups showed a variety of different behavioral patterns in response to Sucrose and Shock CSs. To identify and quantify potentially different behavioral states, I performed an unsupervised trial-by-trial clustering of behavioral responses to CSs based on automatic pose estimation, and found that Nt knockout reduces the number of trials where mice showed active behavioral responses to CSs.

Taken together, these findings indicate a neuropeptide that signals valence in the BLA, and show that NT is a critical modulator for assigning positive and negative valence in amygdala neurons during associative learning.

Neural circuits encoding negative valence and punished reward seeking (Ph.D.)

Dopamine (DA) is one of the major neuromodulators that signal reward and motivation. Studies have shown that DA firing exhibits aphasic pause in response to aversive stimuli, which is thought to mediate behavioral avoidance and punishment learning. However, it was unclear how aversive stimuli could cause DA inhibition, largely because the underlying neural circuits were unknown.

In graduate school, I utilized multiple techniques including optogenetics, in vivo electrophysiology, and endoscopic calcium imaging, to illustrate the role of the rostromedial tegmental nucleus (RMTg), a major inhibitory input to DA neurons, in driving DA inhibition (Li et al., 2019a, Elife) and mediating punished reward-seeking behavior (Li et al., 2019, Neuron). By combining mono-synaptic rabies tracing with cFos immunostaining and in vivo electrophysiology, I identified that a di-synaptic input from the rostral entopeduncular nucleus to the RMTg via the lateral habenula encodes negative valence (Li et al., 2019b, Elife) and cocaine avoidance (Li et al., 2021, J Neurosci).

In collaboration with other lab members, we discovered that the individual differences in cocaine avoidance are correlated with their RMTg activity (Parrilla-Carrero et al., 2022, J Neurosci) and are highly heritable (Eid et al., 2019, BioRxiv).

Measuring serotonin release in response to acute stress (Pre-doc)

My main project during my master’s degree was to study the effects of chronic amphetamine withdrawal on stress-induced serotonin release to limbic structures. Using in vivo microdialysis, I found that restraint stress induced serotonin release into the central nucleus of amygdala and the ventral hippocampus. In rats underwent chronic amphetamine withdrawal, the stress-induced serotonergic response was enhanced in the amygdala and suppressed in the hippocampus, which was blocked by the local infusion of glucocorticoid receptors antagonists (Li et al., 2014, Eur J Neurosci).