Integrative Neurobiology

Synapse and circuit physiology

As a group, the Guoping Feng and Zhanyan Fu teams’ focus is to translate genetic findings of neuropsychiatric disorders into neurobiological mechanisms and facilitate the development of therapeutics. Their research so far has made major advances in understanding the cellular physiology and circuitry mechanisms that underlie neuropsychiatric disorders — in particular, autism spectrum disorder (ASD), schizophrenia, and attention-deficit/hyperactivity disorder (ADHD) — with the state-of-the-art combinations of behavior, circuits, physiology, and genetics.

The main goal of the Synapse and Circuit Physiology team is to understand how synapse and circuit functions are perturbed and the role of such perturbation in neuropsychiatric disorders such as ASD, schizophrenia and ADHD. Studies mainly involve comprehensive electrophysiological assessments ranging from classical to optical electrophysiological techniques. They are working to pinpoint the neuronal circuits involved in neuropsychiatric disorders and to ultimately provide insights into the search for electrophysiological biomarkers and novel effective treatments for the disorders.

Guoping Feng also leads the New Developmental Disease Models team, focusing on the creation of new animal disease models for understanding the pathological mechanisms of brain disorders and the development of new approaches to effective treatment. With the development of new genome engineering technologies such as CRISPR, it is becoming increasingly feasible to apply these molecular tools in a wider range of species. The team is characterizing and developing genetic models of social, learning, and other behaviors in different animals.

In addition, a group led by Bernardo Sabatini and Adam Granger is developing new methods for characterizing the cell-type specific synaptic connectivity in the cerebral cortex. Convergent lines of evidence indicate that neuropsychiatric disorders like schizophrenia involve disordered synaptic function in the cerebral cortex, but we lack robust methods to systematically measure changes in cell-type specific synaptic connections in the mouse brain. The Sabatini/Granger group is pursuing multiple methods for characterizing cortical circuit connectivity in an unbiased and standardized fashion, including viral-based approaches, spatial transcriptomics, slice electrophysiology, and optogenetics. The goal is to identify common circuit defects in mice carrying different schizophrenia and bipolar risk alleles to understand the neurobiological mechanisms of these disorders and identify promising therapeutic targets.

Neuroimmune Interactions

The research in the Stevens laboratory is devoted to understanding the mechanisms by which neuron-glia and neural immune interactions facilitate the formation, elimination, and plasticity of synapses in heath and disease. In particular, the lab is focused on the role of microglia and the classical complement cascade in synaptic pruning and circuit refinement using a combination of molecular, electrophysiological, biochemical, and high-resolution imaging approaches in several model systems. A deep understanding of the mechanisms by which these pruning pathways are regulated and dysregulated in the developing brain could provide new insight into novel biomarkers and therapies in neuropsychiatric, neurodegenerative, and other brain diseases.

Developmental Neurobiology

The goal of the Fishell laboratory is to understand how the vast variety of inhibitory interneuron subtypes are generated and how they subsequently integrate into the wide array of neural circuits that are embedded in different brain structures. Through exploring the molecular control of these events, it has become clear that perturbation of this process can result in a variety of brain dysfunctions including autism spectrum disorder (ASD), intellectual disability (ID) and schizophrenia. A new and growing interest in the laboratory is therefore aimed at seeing if better understanding of these developmental events can lead to the discovery of new treatments for these disorders.