MAR 11, 2020 1:30 PM PDT

PANEL: Dissecting the circuit logics in the amygdala underlying emotional learning (copy)

Presented at: Neuroscience 2020
  • Professor of Neuroscience, Cold Spring Harbor Laboratory
      Bo Li is Professor of Neuroscience at Cold Spring Harbor Laboratory. He received his Ph.D. in Neuroscience from the University of British Columbia in Canada and was a postdoctoral fellow at Cold Spring Harbor Laboratory and the University of California, San Diego. His laboratory focuses on studying the synaptic and circuit mechanisms underlying aspects of motivated behaviors, such as attention, motivation, and learning and memory, as well as synaptic and circuit dysfunctions that may underlie the pathophysiology of mental disorders, including anxiety disorders, depression and autism. His group integrates molecular, genetic, in vitro and in vivo electrophysiology, imaging, optogenetic and chemogenetic methodologies to probe and manipulate the function of specific neural circuits in the rodent brain, and has made fundamental contributions to our understanding of the cellular and circuit mechanisms underlying behaviors reinforced by punishment and reward, in heathy as well as in pathological conditions. Dr. Li's research has been supported by awards from the NIH, Dana Foundation, Brain & Behavior Research Foundation (NARSAD), Simons Foundation, Human Frontier Science Program and Cold Spring Harbor Laboratory.
    • Associate Professor, Vollum Institute, Oregon Health and Science University
        Dr. Mao is an Associate Professor at the Vollum Institute. She earned her B.S. degree in Biology from Tsinghua University in 1997, and Ph.D. degree in Neuroscience from Johns Hopkins School of Medicine in 2005. She carried out her postdoctoral training with Karel Svoboda, first at the Cold Spring Harbor Laboratory, and then at the Howard Hughes Medical Institute Janelia Research Campus. She established her laboratory at the Vollum Institute in 2010. Dr. Mao's laboratory is interested in elucidating brain circuit mechanisms underlying animal behaviors, such as sensori-motor interactions and motor control, and understanding how these circuits are changed and modulated by disease, brain state, and behavioral context.

        Dr. Mao's laboratory develops and implements cutting-edge technology including modern anatomy, computation and machine learning, genetics, imaging, and functional circuit mapping in the mouse model to examine the principles governing neuronal connectivity and their regulation. She serves on the Board of Reviewing Editor for eLife, the advisory board of Neuroscience Next, and the Editorial Board of Frontiers in Synaptic Neuroscience and Neural Circuits. She has received three Brain Initiative awards, as well as continuous support from traditional NIH-funding mechanisms.
      • Scientist/Associate Professor, Vollum Institute, Oregon Health & Science University
          Haining Zhong is a Scientist and Associate Professor at the Vollum Institute of Oregon Health & Science University. He received his Ph.D. in Neuroscience from Johns Hopkins School of Medicine and did postdoctoral training at the Cold Spring Harbor Laboratory and then at the Howard Hughes Medical Institute. Dr. Zhong's lab develops technologies that enable the real-time microscopic visualization of otherwise difficult-to-measure properties associated with brain connectivity and plasticity. His lab also uses these technologies to study the cellular and circuit mechanisms underlying animal behavior, learning and memory in rodents. Related to the current presentation, his lab was the first to achieve in vivo imaging of intracellular cAMP/PKA signaling activities with cellular resolution during animal behavior. This allows him and collaborators to investigate when and where the cAMP/PKA pathway and its upstream neuromodulator transmission happen during different animal behaviors. Dr. Zhong is the recipient of the NARSAD Young Investigator Award and NIH Director's New Investigator Award.


        Learning is often an emotional process. Emotional stimuli with different valences, such as threat and reward, can transform an otherwise neutral sensory input into one that can trigger distinct behavioral outcomes, such as defensive versus reward-seeking behaviors. The amygdala, a structure deep in the brain, plays an essential role in such emotional learning. By integrating sensory information with signals of negative or positive valences, the neuronal circuits within the amygdala are modified during emotional learning. However, how individual emotional stimuli differentially modify the amygdala to mediate the defined, sometimes opposite behavioral outcomes is largely unknown. The overarching goal of our collaborative project is to elucidate the logics and mechanisms underlying differential emotional learning at the level of neuronal circuits. A crucial step forward is to determine the activities of individual neurons within discrete amygdala circuits before, during, and after learning tasks. However, this goal is challenging to achieve. First, the amygdala is buried deep within the brain, making it difficult to access by imaging methods, such as calcium imaging, which is the technique of choice for interrogating neuronal activities with cellular resolution over large neuronal populations. Second, stress and reward signals are in part encoded as neuromodulatory activities, which have been difficult to measure especially in behaving animals. Adding to the difficulty, the identity of individual amygdala circuits, as well as where each circuit receives inputs and where it sends outputs, are only partially understood.

        In on-going progress, the team of three co-PIs meets these challenges by integrating the cutting-edge, complementary technological advances from each laboratory. In defined emotional learning behavioral paradigms we can now image calcium as a proxy for neuronal activity in the amygdala by performing two-photon imaging via a tiny GRIN lens (Φ~0.5 mm), which offers optical access to deep brain structures even in behaving animals. To establish a readout for stress/reward-induced neuromodulatory signals, we have successfully imaged the activity dynamics of the cAMP/protein kinase A (PKA) signaling pathway, which is a common downstream pathway for many neuromodulators, including norepinephrine and dopamine, by combining novel genetically-encoded sensors with two-photon fluorescence lifetime imaging microscopy and GRIN lenses. In conjunction, we are performing whole-brain high-resolution imaging and computation-based anatomical circuitry analyses to dissect novel functional subdivisions of the amygdala and identify the input-output of each subdivision with cell-type specificity. Looking forward, we will integrate the advances in these three aspects to systematically map circuits and determine how neurons in each amygdala circuit are recruited by and contribute to the generation of valence-specific behaviors.

        Learning Objectives:

        1. Introducing the important roles of amygdala in emotional learning and the challenges in understanding it.

        2. Presenting the ongoing progresses in meeting the challenges towards dissecting the circuit logics of amygdala-based emotional learning.

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