Research in the lab of Dr. Izumi Sugihara
Analysis of projections of single axons
Individual neurons (nerve cells) are the basic morphological and
functional units of the nervous system. Therefore, understanding how the nervous system functions requires an
understanding of the morphology and physiology of individual neurons. Neurons often have a long process (axon) that
extends from the cell body and can project to places in the nervous system far
from where the cell body is located. The
rough projection patterns of many groups of neurons have been determined using
a variety of conventional techniques. The
projection patterns of individual neurons, however, have rarely been completely
determined. In other words, only for a
very limited number of kinds of neurons do we know exactly how the axon of an
individual cell extends and bifurcates, and where its branches terminate. Knowledge of the exact projection patterns of
individual neurons is much more useful than the general information about a
pathway obtained with conventional techniques; it represents the precise
organization of the nervous system.
We have developed a system to analyze the complete axonal morphology (projection pattern) of individual neurons efficiently. This system includes a way to label a small number of neurons, histochemical visualization of the labeled neurons in serial brain sections, and computer-aided reconstruction of the axonal trajectory of each labeled neuron. We have been investigating the input and output axons of the rat cerebellum. However, the methods, which we have been developing, are applicable to other brain areas. We have been publishing the results worked out by graduate and undergraduate students. Some of our results have been used in figures in famous international textbooks of neuroscience and neuroanatomy.
Analysis of the cerebellar compartmentalization
When cerebellar damage results from devastating "cerebellar degeneration" diseases, injury, or vascular diseases, it becomes difficult to move the body and/or extremities smoothly. These symptoms are collectively called "cerebellar ataxia". Unlike damage to motor regions in the
cerebrum, spinal cord or peripheral nervous system, cerebellar damage does not
cause paralysis, but causes movements to become unsmooth and clumsy. Cerebellar control of movement is a completely
unconscious yet sophisticated process; it is nearly impossible for someone with
a normal cerebellum to mimic the symptoms of cerebellar ataxia. How the cerebellum controls movement is a big
question that remains essentially unsolved. A hint to the answer to this question is that there is a fine functional
compartmentalization of the cerebellum. It is because of this compartmentalization that different types of
cerebellar ataxia (like ataxic gaits, ataxic hand/finger movements, problems in
reflexes or thick tongue) result depending on the cerebellar area that is
damaged. Our approach to investigating the cerebellum is focused on the mechanisms
of the cerebellar compartmentalization. We are trying to
determine exact compartmentalization of the entire cerebellum from different
aspects, including molecular expression patterns. We are also trying to determine
compartment-specific input and output neuronal connections by the single axon
reconstruction approach described above in order to understand how neuronal
connections are related to control of specific types of movements.