RESEARCH

The McIntyre Lab is part of the Department of Neuroscience and the University Center for Smell and Taste at the University of Florida College of Medicine.  We study the cellular and molecular mechanisms underlying olfactory function. The lab is interested in mechanisms to treat the loss of the sense of smell (anosmia), and how odor information is modulated in the olfactory bulb. We use employ a wide variety of techniques including gene therapy, confocal microscopy, calcium imaging, electrophysiology molecular and cell biology and transgenic mouse models.

Gene therapy for Congenital Anosmia
Olfactory disorders affect a significant portion of the population. Disorders in the sense of smell can be caused by aging, traumatic injuries, infections and genetic mutations. Defects in ion channel function underlie an emerging class of human genetic diseases, termed channelopathies. In addition to other sensory defects, channelopathies have been shown to cause the loss of the sense of smell. Our research aims to identify mechanisms by which specific ion channels regulate olfactory signaling, how these are disrupted in disease states and the ability to correct channel defects. We are applying gene therapy approaches to study the ability to restore olfactory function in animals models of channelopathy induced anosmia. These studies will combine behavioral tests to assay olfactory function at the system level as well as electrophysiology and molecular techniques to address changes on the cellular level. The ultimate goal of this work is to demonstrate functional recovery of olfactory function in channelopathy models for the further development of treatments for human patients. This work is funded by a R00 award through the National Institute on Deafness and Other Communication Disorders. Read More Here

Neuromodulation of olfactory bulb neurons
Primary cilia are ubiquitous organelles found on many cell types, including neurons of the CNS. These structures are a type of cellular “antenna” that function to sense cues in the extracellular environment. However the precise roles for these organelles on neurons in the brain remain unknown. Many of these cilia possess G-protein coupled receptors for neuromodulatory signals. We are working to identify the particular GPCRs found in the cilia of different subtypes of olfactory bulb neurons. We will be using calcium imaging, electrophysiology and behavior testing to analyze the importance of cilia, and the receptors localized there, on these neurons The aim of this project is to elucidate the role for cilia in modulating neuronal function in the olfactory bulb.

Cilia mediated neuromodulation of reward pathways

Substance use disorders are a significant health issue in the US, costing tens of thousands of lives and hundreds of billions of dollars annually. The neural mechanisms that underlie substance use disorders are complex, and impacted by numerous outside factors. These additional actors include several neuromodulatory peptides that are associated with physiological states such as hunger and satiety. Within the past ten years it has been discovered that several of the receptors for these neuromodulators are enriched in the primary cilia of neurons.  The goal of this research is to determine how signaling through the primary cilium contributes to integration of neuromodulatory signals that regulate responsiveness to drugs of abuse and related behaviors.  We are using pharmacological and viral-mediated gene delivery approaches to study the role of cilia on GABAergic and dopaminergic neruons in regulating these behaviors. We are interested in understanding the consequences of cilia loss, particularly in the nucleus accumbens, for the rewarding effects of cocaine and morphine. In addition to using ciliary signaling to identify novel modulators of these behaviors. This project uses a variety of techniques including behavior experiments, viral manipulations, calcium imaging and microscopy. Cilia represent a unique neuronal signaling environment and a better understanding of this could lead to novel targets for therapies aimed at reducing substance use.

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