Email: keith [dot] murai [at] mcgill [dot] ca
Tel.: 514-934-1934 ext. 43477
Associate Professor | Neurology & Neurosurgery, Medicine (Dept. & Faculty)
Researcher | Research Institute of the McGill University Health Centre
In the laboratory, we use molecular, biochemical, and cell imaging approaches to study the synaptic function of proteins and signaling complexes. Understanding how synapses are modified will likely yield important insight into cognitive function and mental disease.
Regulation of synaptic morphology and function
Synapses are specialized sites of cell to cell attachment that are critical for neural cell communication. Information is stored in the brain by creating, remodeling, and modifying the effectiveness of synapses. Recently, the diversity of molecules that are localized at excitatory synapses has begun to be revealed. These proteins (cell surface, scaffolding, and signaling molecules) are networked together and establish the structural framework of the synapse. Many of these proteins are critical for synaptic transmission and/or long-term synaptic plasticity. In most cases, however, the mechanistic details behind their function at synapses remains unknown.
The major research interest of the laboratory is to understand how proteins (neural and glial) and their signaling complexes regulate synaptic morphology and function. Remarkably, in certain brain regions such as the hippocampus (an area important for learning and memory), neurons have the potential to undergo morphological changes into adulthood. In particular, the dendritic spines, the small protrusions on dendrites that receive the vast majority of excitatory input in the brain, show extensive geometrical remodeling. They can change their morphology on the order of minutes, suggesting that alterations in neural activity can quickly alter spine parameters. These modifications may enable rapid adjustments to ionic balance (i.e. Ca2+), biochemical, and protein signaling events that impact postsynaptic physiology. Proper spine structure, motility, and organization is likely critical for synaptic efficacy while abnormalities may be related to mental retardation associated with conditions such as Down, Williams, and fragile-X syndromes, and cognitive impairments linked to schizophrenia. Thus, identifying the mechanisms that regulate the structural features of spines is important for understanding elements of synaptic plasticity, cognitive function, and mental disease.
One project in the lab studies the role of Eph receptors and their ephrin ligands. The Eph receptors comprise a large family of receptor tyrosine kinases and are found in a wide variety of developing and mature tissues. Recently, the Eph receptors and ligands have been localized on postsynaptic membranes of neurons, especially in regions of the brain that show high neural plasticity. These proteins represent excellent candidates for defining synaptic morphology since they are important regulators of cellular interactions and morphology during development of the nervous system.
Another research interest in the lab is to understand how the relationship between neurons and glia influences brain plasticity. Glia can regulate synapse number and maturation during development and display calcium excitability, can handle neurotransmitter, and buffer the extracellular milieu. Indeed, the complex interplay between neurons and glia is necessary for synaptic transmission. We are interested in determining the mechanisms that are important for neuron to glia and glia to glia communication.