Laboratory of
Neural Circuits and Animal Behavior
Research Interests

Animals have numerous behaviors, which are controlled or modulated by the activities of neural circuits. Mechanistic understanding of animal behavior at the circuitry level is one of the ultimate challenges of Systems Neuroscience.  By combinatory use of techniques including multichannel recording, transgene, optogenetic / chemogenetic manipulation, single cell electrophysiology and behavioral study, we are investigating the relationship between the activities of neural circuits and several types of behaviors of Rat / Mouse. The research in our lab is aimed to illustrate the neural mechanism underlying certain mammalian behaviors at the level of neural circuit.

Mechanism of Mouse Defensive Behavior
Defense is a basic survival mechanism when animals are facing dangers. Previous studies have suggested that the midbrain periaqueductal gray (PAG) is essential for the generation of defensive reactions. Here we showed that optogenetic activation of pyramidal neurons in the PAG in mice was sufficient to induce a series of defensive responses (including running, freezing and avoidance). However, the endogenous neural dynamics of PAG underlying defensive behaviors still remains elusive. Using chronic extracellular recording, we recorded the spiking activities of PAG neurons in freely behaving mice exposed to natural threats (rats). We observed that there exist distinct neuronal subsets within PAG participating in different aspects of defensive behaviors. Our results demonstrate the important role of PAG neuronal activities in the control of different aspects of defensive behaviors, and provide novel insights for investigating defense from an electrophysiological perspective.

Mechanism underlying Waiting Control of Rat
The willingness to wait for delayed reward and information is of fundamental importance for deliberative behaviors. The orbitofrontal cortex (OFC) is thought to be a core component of the neural circuitry underlying the capacity to control waiting. However, the neural correlates of active waiting and the causal role of OFC in the control of waiting remain largely unknown. Here we trained rats to perform a waiting task, and recorded neuronal ensembles in OFC throughout the task. We observed that OFC neurons displayed heterogeneous neural dynamics to different phases of the waiting task. Activities of subset OFC neurons correlated with the waiting behavior, and even predicted the waiting outcomes. Furthermore, lesion or inactivation of OFC impaired the waiting performance, and optogenetic activation of OFC during waiting improved it. These findings reveal that the neural activity in OFC underlies the executive control of waiting and plays a causal role in this process.

Mechanism of Rats Attention and Attention Shift
The anterior cingulate cortex (ACC) has long been thought to function in detection of conflict between sustained attention to a task target and distractors. However, it is unclear whether ACC serves to sustain attention itself. Here, we devised a task in which the time course of sustained attention could be controlled in rats, and then, using lesion experiments, applied it to demonstrate an ACC function in sustained attention. We then identified specific ACC neurons either persistently activated or suppressed during that period of attention. We propose that these neurons underlie sustained attention based on the fact that target modality had minimal influence on their activities, and distracting external sensory input during the attention period did not perturb persistent neuronal activities.

In daily life, humans have to consistently process and integrate information of stimuli in different sensory modalities simultaneously. Voluntary top-down attention is a key mechanism to select relevant subsets of sensory information for detailed and effective processing and to actively suppress distracting irrelevant sensory information. Posterior parietal cortex (PPC) has been implicated to play a role in shift attention from one perceptual dimension of a stimulus to another. This study examined how PPC is involved in attention shifting from one modality to another. We trained rats to perform a bimodal attention shift task. In this task, subjects have to selectively attend to a stimulus in one modality and respond to it, whereas the stimulus in the other modality has to be ignored. The subjects must alternate which modality they select multiple times within each session. Neurons in PPC were recorded during this task. We found that PPC neurons showed similar response pattern to the attended stimulus either when it was presented alone or in combination with a distractor. Response to ignored distractor was inhibited. These results suggest that PPC may play an important role in modality gating.

Mechanism of Decision-Making in Rat
The neural mechanisms of decision-making in primates have been hot spots in neuroscience for decades. Previous studies show that the Lateral intraparietal area (LIP) of monkeys can receive and integrate visual signals, and these properties of LIP are essential to subsequent eye-movement responses. These results indicate that primates can accumulate evidence during perceptual (visual) decision-making and LIP plays key role in it. Recent studies demonstrate that rat can also optimally accumulate evidence for decision-making. We set out goal to dissect the circuit mechanism underlying evidence-accumulating decision-making process.We will examine the neuronal activities in orbitofrontal cortex, posterior parietal cortex and media prefrontal cortex during the task.  Pharmacological and optogenetic manipulation will be applied to test the relationship between the activities in different brain regions to the behavior. We aimed to 1) identify which brain region in the rat brain play the role similar to that of LIP in monkeys, 2) dissect the mechanism how accumulation of evidence of sensory signals is achieved by neural circuits in rat brain.

  

Wang, Zuo-Ren, Ph.D.

Deputy Director,Senior Investigator
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