|Institution||College of Medicine|
|Department||Neural and Behavioral Sciences|
|Address||500 University Drive Hershey PA 17033|
Assistant Professor of Neural and Behavioral Science
My laboratory has worked in conjunction with that of Dr Travagli for several years, exploring our common interest in the organization of autonomic homeostatic circuits. Our preliminary studies led us to propose that brainstem autonomic circuits are pathway specific. That is, a neuron’s properties (biophysical, neurochemical, pharmacological) in combination with its synaptic connections to and from other central nuclei define it as belonging to a distinct autonomic pathway. Under this proposal, autonomic circuits are segregated into distinct functional lines and subgroups of neurons are responsible for the integration of homeostatic functions. Our future studies will investigate these circuits with the aim of identifying the molecular and cellular determinants that malfunction or maladapt in pathological states such as obesity or diabetes and the role these factors play in the plasticity and adaptations necessary to respond to the changing environment.
More recently, the work of our laboratories has led us to propose that autonomic brainstem circuits are not the stereotyped relay networks they have been assumed to be but, instead, are capable of rapid adaptation in response to changing conditions. Those factors that malfunction in diabetes, for example, involve a different set of neurons and circuits with respect to the factors that are altered in cardiovascular disorders such as hypertension or respiratory disorders such as chronic cough or airway hyperreactivity. These adaptations are highly specific in terms of the neuronal populations they target and imply that the visceral parasympathetic output can be tailored to homeostatic requirements in an on-demand fashion. These adaptations may also be triggered inappropriately, however, suggesting that peripheral injury (inflammation, mechanical or chemical insult) or disease (diabetes or obesity) may induce longer-term or unwelcome alterations in autonomic brainstem circuits.
Plasticity within the parasympathetic autonomic system does not appear to be restricted to circuits within the brainstem, though. My own laboratory has begun to focus on the sensory vagus and the role that plasticity plays with respect to alterations in peripheral sensation and signaling. This has led to the hypothesis that the vagal sensory neurons and nerve terminals are open to constant modulation by humoral, paracrine and feeding-related hormones. I have focused my efforts in particular to the study of hyperglycemia, as a pre-diabetic state. Glucose, for instance modulates the number and function of neurotransmitter/modulator receptors (5-HT3 and GLP-1 receptors, for example) on vagal afferent neurons and nerve terminals, hence regulates the magnitude or duration of the sensory response. Short-term exposure to a diet high in fat, however, attenuates this ability of glucose to modulate the responsiveness of vagal afferents to glucose, however, long before development of obesity or loss of glycemic control suggesting that loss of glucoregulation precedes, and may even contribute to, these conditions.
To investigate these hypotheses, our laboratories use the following techniques
? Patch clamp electrophysiology (from brain slices and dissociated primary culture)
? Morphological analyses
? Single-cell RT-PCR
? In vivo studies of visceral (mainly subdiaphragmatic) functions including gastric motility and emptying
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