The proper functioning of oral-facial motor systems is necessary for the survival of humans. The ingestive behaviors of mammals begins with suckling and progresses to drinking and chewing. Presently, there are very few studies addressing how the brain is organized to produce these behaviors. Even less is known about the etiology of various oral-motor disorders such as tardive dyskinesia, bruxism, and myofacial pain dysfunction syndromes. The long-term goals of this research are to understand both the mechanisms underlying the central nervous system control of normal jaw movements that occur during activities such as drinking and chewing, as well as the abnormal jaw movements that occur during various disorders.
The specific aims of this proposal are to continue investigations, at the cellular level, into the neuronal mechanisms controlling trigeminal neuronal membrane excitability and burst discharge that are associated with the critical transition from primitive suckling behavior to adult-like mastication in the rat. We will combine whole cell patch clamp recording methods of neurons within the trigeminal nuclei responsible for oral-motor activity (mesencephalic V neurons and trigeminal interneurons) in brain slices with microstimulation, neurochemical, and mathematical modeling techniques to more fully elucidate 1) the mechanisms controlling excitability, and 2) the local chemical and electrical microcircuitry of these neurons. The project is divided into two Specific Aims.
In Specific Aim I we will determine the locations of, and ionic mechanisms underlying, intrinsic burst generation in Mes V and trigeminal interneurons in the vicinity of the trigeminal motor nucleus and test the hypothesis that the underlying conductances are substrates for modulation by metabotropic glutamate receptor (mGluR) and serotonergic (5-HT) receptor activation.
Specific Aim II focuses on characterizing the local excitatory and inhibitory chemical and electrical synaptic interactions that occur between distinct trigeminal neurons, and the modulation of these interactions by activation of mGluR and 5-HT receptors. The results of the proposed studies will provide insights into the local microcircuitry and the cellular mechanisms controlling discharge of distinct populations of trigeminal neurons involved in production of jaw movements at distinct developmental time points, and will serve as a cellular foundation for creation of neuronal models of masticatory rhythm and burst pattern generation.
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