Anatomy and Neuroscience
- Elucidation of functional integration in the cerebrum
- Elucidation of cerebral cortex construction by cell migration
- Elucidation of the molecular mechanism for neuron migration from the cerebral cortex
- Elucidation of cerebral cortex development and diseases that arise from its dysregulation
- Elucidation of synapse formation at the molecular level
Mechanisms that form and integrate neural circuits for brain function in the cerebral cortex
The human brain is the master control center of the body and controls how we act and think. One could easily argue that the brain makes us who we are, yet little is understood about how the brain functions. The cerebral neocortex, which exists only in higher animals, is the foundation of intelligence. It is also a structure with extreme complexity and can be considered a brain within the brain. Our lab aims to elucidate mechanisms that underlie functional integration in the brain, brain formation and development, and diseases caused by brain dysfunction as efforts to find new treatments.
It has been challenging to elucidate the mechanism of neural circuit formation in the neocortex by using conventional methods, owing to the complexity of the regions involved (e.g. visual and motor cortex). It is known that neurons do not work independently in the neocortex,, but in groups that make up functional units that interact with one another. Therefore, our group focuses on corticogenesis and studies how each of these units forms and functions.
The neocortex consists of approximately 80% glutamate excitatory neurons and the remaining are morphologically and functionally diverse GABAergic nerve cells. Excitatory neurons arise in the ventricular zone in the deep cerebral cortex, then migrate outward to form the neocortex. However, precise mechanism that regulates the initiation of migration from the ventricular zone is still unknown. The lab has identified and cloned FILIP, a molecule located in the ventricular zone in efforts to examine this mechanism. We found that FILIP promotes degradation of filamin A, an actin binding molecule, which in turn inhibits cell mobility. This was the first study in the world to demonstrate the negative regulation of neocortical cell migration [1].
Recently, there has been an emphasis on the type of information communicated from one unit to another, how these units work together, and how they regulate emotions and memories. Also, how the breakdown of such regulatory elements is related to disease (e.g. developmental disorders, psychiatric disorders, dementia, etc.) is also of immense interest (Figure 1: Two-photon microscopy images of axons forming connections in the cerebral cortex.)
Figure 1: An inter-areal connection visualized with GFP
The lab is studying the molecular mechanism of circuit formation in nerve fibers that extend from the cerebral cortex to the subcortex. Furthermore, research is being conducted on the limbic system and circuitry involved in bridging the cerebral cortex to the cerebellum. (Figure 2: Expression of fluorescent protein and visualization of the corticospinal tract).
Figure 2: Corticospinal tract
These research results will be used toward the treatment of disordered nerve fibers and nerve function.
Reference:
1. Nagano et al. Nature Cell Biology 4 (7): 495-501, 2002.
