Welcome to the website of the laboratory of Kamran Khodakhah at Albert Einstein College of Medicine!
THE BIG PICTURE
The cerebellum coordinates movement and maintains balance by generating precise timing signals for the proper contraction of agonist and antagonist muscles. Failure of the cerebellum to generate precise timing signals results in movement disorders. In order to generate these precise timing signals, the cerebellum receives and integrates information from cortical areas and all sensory modalities. This information is processed primarily by the circuitry of the cerebellar cortex, the sole output of which are Purkinje cells. These spontaneously active cells encode the timing signals required for motor coordination and balance in their rate and pattern of activity. Purkinje cells relay processed information to the deep cerebellar nuclei (DCN), which further process and send signals to various target areas.
Our laboratory is interested in examining the cerebellum from the single-cell level up to the behaving animal. Specifically, we are interested in examining the intrinsic properties and information processing of Purkinje cells and DCN neurons under normal and pathological conditions. Our ultimate goal is to understand 1) how the cerebellum generates precise timing signals; and 2) how its dysfunction leads to motor impairments, namely ataxia and dystonia.
By elucidating the cellular and synaptic mechanisms of cerebellar function we hope to not only better understand the role of the cerebellum in motor coordination, but also to provide potential therapeutic targets against cerebellar diseases. Our studies on the mechanisms of regulation of intrinsic excitability in Purkinje cells have provided plausible explanations as to why mutations in certain ion channels cause ataxia in several human hereditary ataxia diseases.
Currently, our lab is interested in understanding:
◊ how alterations in calcium homeostasis modulate Purkinje cell activity
◊ the mechanisms that give rise to, and regulate, the intrinsic spontaneous activity of Purkinje cells
◊ how Purkinje cells integrate and encode synaptic input
◊ information transfer between the cerebellar cortex and the DCN
◊ the role of the cerebellum in dystonia ◊ the mechanisms underlying cerebellar ataxia
To address these issues, we use a combination of electrophysiological, optical, modeling, and behavioral methods. To complement our studies, we often take advantage of transgenic and mutant mice as animal models of human hereditary ataxias.