Laboratory of
Neural Circuit Development
Research Interests

Deficits in neuronal connectivity have been implicated in many neurological disorders, highlighting the importance of understanding how the brain is progressively organized from billions of individual neurons. There is increasing evidence showing that neurons in local brain regions connect with one another in a specific manner to assemble different types of microcircuits. These local microcircuits from different brain regions are then linked by long-range projection neurons to form the brain circuits underlying various cognitive and motor functions. As basic building blocks of brain circuits, microcircuits represent a very attractive area for studying the development of brain circuits and to investigate the deficits underlying neurological disorders. Based on the combination of multiple whole-cell recording, long-term in vivo two-photon imaging,calcium imaging, optogenetics and genetic manipulations, our long-term research interest is to understand neural microcircuits embedded in the mammalian brain and their roles in health and disease.

Our current goals are:
1. To reveal the mechanisms underlying cell lineage-dependent microcircuit formation.
Minicolumns are perceived as the most basic information-processing unit in the neocortex. Recent studies on cell lineage have revealed that sister pyramidal cells provide the structural and functional basis for the minicolumns. However, the molecular mechanism underlying lineage-dependent microcircuit remains unclear. We aim to advance our understanding of the specification of synapse formation between neurons. This will also provide new insight into the pathogenesis of developmental brain disorders at the neural circuit level.

2. To investigate the capillary-related development of microcircuits.
Blood flow is tightly controlled by local neuronal activity. Many brain diseases, such as autism spectrum disorder and Alzheimer's disease, are characterized by abnormalities in regional cerebral blood flow. It is thus very interesting to understand how the development of microcircuits is coordinated with that of adjacent capillaries to locally control blood flow. By expanding our knowledge on neurovascular coupling, we may further understand the pathophysiology of some devastating neurological diseases, as well as the mechanisms underlying common brain imaging techniques such as functional MRI.

3. To elucidate the mechanisms linking different microcircuits.
We will also explore how different microcircuits from the same or different brain regions are linked together to form more complex neural circuits. Meanwhile, we will also examine whether deficits of many neurological diseases, such as autism spectrum disorders and Alzheimer's disease, result from the deficits in linking different microcircuits.


Xu, Hua-Tai, Ph.D.

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