This proposal describes a high risk, high impact project using an optogenetic approach to determine how visceral neurons associated with satiey modulate the taste system. We have created a novel viral vector (AAV-9, PRSx8-ChR2(h134r)-mCherry) that expresses channelrhodopsin-2 (Chr2) and mCherry under the control of a Phox2-selective promoter that labels catecholaminergic neurons containing norepinephrine and other non-GABAergic viscerosenory neurons. A second optogenetic approach will target catecholamine neurons more specifically using a transgenic mouse that expresses Cre under the control of a dopamine-? hydroxylase promoter (D?HCre/0) and a cre-dependent virus driving ChR2 expression. Neurons in the caudal brainstem including catecholamine neurons are intimately associated with visceral signaling underlying satiey mechanisms and glucoprivic-induced feeding, but where and how they modulate taste signals is unknown. Although catecholamine neurons are clustered in groups, e.g. A1 &A2, these clusters are embedded in a more heterogeneous population of cells making it difficult to study specific neural pathways. Optogenetic techniques allow defined neuron types to be specifically activated. Neuronal DNA is modified by inserting a gene expressing a light-sensitive channel (protein) capable of depolarizing the neuron membrane. Following neuronal transduction with the genetic construct, optical stimulation with a laser or high-intensity LED tuned to the optimal frequency of the light-sensitive channel will subsequently stimulate and depolarize those neurons genetically defined by the promoter. Recent work suggests that significant interactions between caudal solitary nucleus neurons sensitive to visceral signals and feeding circuits occur through local brainstem pathways including intrasolitary pathways. The outcomes of our proposal will thus (1) provide a novel technical approach to determine how a specific group of visceral-sensitive neurons modulate gustatory neurons and (2) determine if a previously unexplored brainstem intrasolitary pathway contibutes to taste/visceral integration.

Public Health Relevance

Taste and visceral input from the gut are two of the many factors that control ingestive behavior and dysfunction of this interaction can contribute to feeding disorders. Because catecholamines are part of the limited pharmacological approach to treating obesity, determining how and where catecholamines modulate taste/visceral interactions is relevent to therapeutic approaches to clinical conditions associated with obesity, cachexia and the postsurgical effects of bariatric surgery

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Exploratory/Developmental Grants (R21)
Project #
1R21DC013676-01A1
Application #
8773145
Study Section
Somatosensory and Chemosensory Systems Study Section (SCS)
Program Officer
Sullivan, Susan L
Project Start
2014-06-01
Project End
2016-05-31
Budget Start
2014-06-01
Budget End
2015-05-31
Support Year
1
Fiscal Year
2014
Total Cost
$231,000
Indirect Cost
$81,000
Name
Ohio State University
Department
Dentistry
Type
Schools of Dentistry
DUNS #
832127323
City
Columbus
State
OH
Country
United States
Zip Code
43210