Neuronal Nicotinic Receptors (nAChRs) and Sleep-Related Epilepsy The cerebral cholinergic system contributes to the regulation of vigilance and cognition. Malfunction of cholinergic transmission is apparent in many neuropathologies, including neurodegenerative diseases, although its aetiologic and pathogenetic role is unclear.We are studying the main physiological and morphological features of the nicotinic branch of the cholinergic system, in the adult thalamocortical system. This focus is suggested by the possible application of our studies to understand some forms of autosomal dominant nocturnal frontal lobe epilepsy. This is the only neurologic disease in which solid evidence of an aetiologic role of altered cholinergic transmission is available, because of mutations of certain subunits of the nAChR.
Determining the cerebral nAChR physiology requires: i) distinguishing the role of the nAChR subunits, ii) profiling the nAChR expression and function in different cell populations (including glia and developmental stages of circuit maturation), iii) dissecting the pre-, post- and extrasynaptic receptor's functions and their modulation by other transmitters and neuropeptides, iv) clarifying the balance between tonic and phasic ACh actions, v) studying how these functional features contribute to the physiology of the thalamocortical network.
These aims will be carried out by applying electrophysiological, neuroanatomical and molecular biological methods (in collaboration with Dr. A. Amadeo, University of Milan) to brains extracted from normal mice and transgenic models of sleep-related epilepsy.
Other ongoing projects
Besides our studies of mutant receptors linked to mendelian sleep-related epilepsies, we have recently begun to address the nAChR involvement in lung cancer cells and the response of these receptors to tobacco-related carcinogens. Moreover, we are continuing a long-term project on the functional interaction between voltage-gated K+ channels, integrin-mediated signalling and cell migration and proliferation, with implications for neoplastic transformation and invasiveness (in collaboration with prof. A. Arcangeli, Univ. of Florence).
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