Michael S. King - US grants

Taste information travels from the mouth to the brain within nerves that terminate in a part of the medulla oblongata called the nucleus of the solitary tract (NST). The NST is interconnected with another part of the brainstem called the parabrachial nucleus (PBN). Both the PBN and NST act as processing and distribution centers for taste information. They send some taste information to higher brain centers so that the taste quality can be perceived. The PBN and NST also send outputs to motor centers in the brainstem that produce motor responses to the taste input.
Within the PBN, there are two distinct regions that respond to taste input. One of these regions (CM/VL) responds best to salt on the anterior tongue while the other (EM/EL) responds best to bitter taste on the posterior tongue. Due to this difference in responses to taste input, it is hypothesized that the two PBN areas control different motor responses. Specifically, it is hypothesized that CM/VL controls ingestive behaviors (like mouth movements and tongue protrusions) while EM/EL controls aversive behaviors (like gapes).
Undergraduate Biology and Psychology students and their faculty mentors, will address these hypotheses by stimulating discrete areas of the PBN while observing motor responses. This procedure will allow the construction of a functional map of the PBN. Specifically, CM/VL and EM/EL will be stimulated in separate groups of conscious rats using implanted electrode-cannula systems. First, these areas will be electrically stimulated while oral motor behaviors are videotaped. Following electrical stimulation, injection of glutamate (an excitatory neurotransmitter) through the cannula into the same location within the PBN will occur. The combination of electrical and chemical stimulation will allow accurate assessment of the specific neural elements responsible for the behavioral effects. The motor responses will be correlated with the histological localization of the stimulation sites. As mentioned, based on previous findings, it is hypothesized that stimulation of CM/VL will generate ingestive behaviors, while stimulation of EM/EL will evoke aversive responses.
This study employs a straightforward strategy to define the effects of taste-responsive PBN regions on oral motor behaviors. The potential impact of the project on the understanding of central processing of taste input and the function of the PBN is substantial. Specifically, elucidation of a functional topography (map) within the PBN would significantly improve the understanding of the central mechanisms producing oral motor responses to taste input.

DESCRIPTION (provided by applicant): The long-term goal of this research is to elucidate the central neural mechanisms underlying feeding-related behaviors initiated by taste input in the rat. Recent studies have focused on the neurochemistry of two brainstem areas that receive gustatory sensory information, the rostral nucleus of the solitary tract and the parabrachial nucleus (PBN). The role of the PBN in the processing of sensory information and the initiation of oromotor responses is particularly intriguing since neurons in the PBN process taste-related sensory information and project to the network of motor neurons in the medulla that controls oromotor behaviors. Suggesting a role for glutamatergic neurotransmission within the PBN in the initiation of oromotor behaviors, microinjection of glutamate directly into the taste regions of the PBN in conscious rats elicits ingestive behaviors like mouth movements and tongue protrusions. Therefore, the first specific aim of the proposed study is to determine the role of glutamate receptors within the PBN in oromotor behaviors elicited by taste stimulation. It is hypothesized that the activitation of glutamate receptors is necessary for normal behavioral responses. Cholecystokinin (CCK) is a gut peptide that has satiety effects. There is some evidence that CCK modulates ingestive behaviors but a specific functional role for CCK and its receptors within the PBN has not been addressed. Therefore, the second specific aim of the proposed study is to determine the role of CCK in the PBN in oromotor behaviors elicited by intra-oral infusion of taste solutions in conscious rats. The hypothesis is that, consistent with its role in satiety, CCK will reduce ingestive oromotor responses to taste input. Both specific aims will be addressed by implanting cannula into the PBN as well as into the oral cavity so that glutamate or CCK receptor blockers can be injected into the PBN immediately prior to infusing taste solutions into the oral cavity in conscious rats. The proposed research is relevant to public health because it will improve the understanding of the neural circuits within the brainstem that control behavioral responses to taste input. These behavioral responses are critical to survival since they result in the acceptance of appropriate foods and rejection of potential toxins. Specifically, data collected during the proposed investigation will determine if glutamate and CCK in the PBN play a critical role in the assessment of ingested substances and subsequent behavioral responses.

DESCRIPTION (provided by applicant): The long-term goal of this research is to elucidate the central neural mechanisms underlying feeding-related behaviors initiated by taste input in the rat. Recent studies have focused on the neurochemistry of two brainstem areas that receive gustatory sensory information, the rostral nucleus of the solitary tract and the parabrachial nucleus (PBN). The role of the PBN in the processing of sensory information and the initiation of oromotor responses is particularly intriguing since neurons in the PBN process taste-related sensory information and project to the network of motor neurons in the medulla that controls oromotor behaviors. Suggesting a role for glutamatergic neurotransmission within the PBN in the initiation of oromotor behaviors, microinjection of glutamate directly into the taste regions of the PBN in conscious rats elicits ingestive behaviors like mouth movements and tongue protrusions. Therefore, the first specific aim of the proposed study is to determine the role of glutamate receptors within the PBN in oromotor behaviors elicited by taste stimulation. It is hypothesized that the activitation of glutamate receptors is necessary for normal behavioral responses. Cholecystokinin (CCK) is a gut peptide that has satiety effects. There is some evidence that CCK modulates ingestive behaviors but a specific functional role for CCK and its receptors within the PBN has not been addressed. Therefore, the second specific aim of the proposed study is to determine the role of CCK in the PBN in oromotor behaviors elicited by intra-oral infusion of taste solutions in conscious rats. The hypothesis is that, consistent with its role in satiety, CCK will reduce ingestive oromotor responses to taste input. Both specific aims will be addressed by implanting cannula into the PBN as well as into the oral cavity so that glutamate or CCK receptor blockers can be injected into the PBN immediately prior to infusing taste solutions into the oral cavity in conscious rats. The proposed research is relevant to public health because it will improve the understanding of the neural circuits within the brainstem that control behavioral responses to taste input. These behavioral responses are critical to survival since they result in the acceptance of appropriate foods and rejection of potential toxins. Specifically, data collected during the proposed investigation will determine if glutamate and CCK in the PBN play a critical role in the assessment of ingested substances and subsequent behavioral responses.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

The proposal seeks funding to renovate a natural science research facility in the institution's Sage Hall. The project will result in 3370 sf of renovated research space serving the Chemistry and Biology Departments. The facility will provided renovated laboratories for Chemistry, Synthetic Chemistry, Computational Chemistry, Aquatic Biology, and Behavioral Neuroscience.

The institution is a small, private university serving 2,222 undergraduate students. Every natural sciences major must complete a research project that spans several semesters as a part of his or her degree requirements. Additional student research is supported by Stetson Undergraduate Research Experience (SURE) grants, and SURE grantees must present their research at both professional conferences and Stetson's own campus-wide annual research symposium.

Research topics planned for the renovated labs include: the binding of organic thiophenes to copper centers with a goal of gaining a better understanding of the copper-thiophene interactions relevant to the desulfurization of fuels; the binding of alkenes to copper centers with a goal of understanding the chemistry of ethylene binding to the plant enzyme ETR1; curcumin and its role in inhibiting oxidative stress in biosystems; drug delivery hydrogels based upon copolymerization of 2-hydroxyethyl methacrylate (HEMA) and 2-hydroxyethyl acrylate (HEA); the neural control of behavioral responses to taste input, the neurophysiology of the rat gustatory system, the influence of catfish biology on the impact of invasive loricariid catfish on a Florida ecosystem, and freshwater ecology.

In addition to providing infrastructure for research by faculty members, the renovation will result in an increase in research opportunities for students from Stetson and for students from a nearby State College who wish to spend a summer working on a research project.

Behavioral responses to taste stimuli include those leading to ingestion (mouth movements, tongue protrusion, etc.) and rejection (gapes, etc.). The neural circuitry required for these behaviors is contained within the brainstem. Several forebrain regions are connected to brainstem taste centers, but the functional roles of these connections have not been determined. Therefore, the specific goal of this study is to determine the behavioral roles of the descending projections from forebrain structures to gustatory centers in the brainstem. The general experimental approach will be to activate the descending projections with implanted electrodes in conscious rats and to observe changes in taste-related behaviors (particularly to salty and bitter stimuli). To understand the mechanisms of the behavioral effects, changes in the location, number and type of neurons in the gustatory brainstem, activated by forebrain stimulation, will be determined using a combination of anatomical and molecular techniques. It is expected that the results of this study will improve our understanding of the neural mechanisms underlying taste-related behaviors and provide a foundation for future research on the role of these pathways in more complex behaviors. The broader impacts of the proposed activities include the involvement of a diverse undergraduate student population in scientific research, enhanced undergraduate student preparation for graduate work in the Biological Sciences, and published findings to disseminate the results of the experiments. Beyond those impacts, the proposed activities will increase interaction among scientists and students at Stetson University, enhance learning, teaching and training in classrooms and laboratories, and promote outreach to local middle- and high-school teachers and their students.