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Principal Investigator: Karina Alvina
Organization: UNIVERSITY OF FLORIDA
Fiscal Year: 2024
Award: $295,048
Funding agency: National Institute on Deafness and Other Communication Disorders
Project Summary
The sense of smell is essential for maintaining full human health and quality of life. It plays an
important role in the detection of environmental dangers as well guiding decisions such as what
foods to eat. However, olfactory processing is influenced by the physiological state of an organism.
Both sleep deprivation and changes in satiety are connected with changes in the function of the
olfactory system. Physiological changes such as these are integrated in the hypothalamus, where
different neuropeptides are expressed by specific populations of neurons. These peptides can
regulate transitions between wakefulness and sleep, or promote feeding behaviors. One peptide
that functions in both promoting feeding and sleep is melanin-concentrating hormone (MCH).
Neurons expressing MCH project to several areas of the brain including the olfactory bulb (OB),
where the MCH receptor, MCHR1, is expressed. This connection represents a previously
understudied pathway providing a potential mechanism for sleep or satiety induced changes in
olfactory function. The proposed research will investigate the role of MCH signaling and
hypothalamic MCH neurons in contributing to odor processing. The aims of this proposal will test
the central hypothesis centrifugal MCH neurons integrate physiological states and regulate
olfactory function. Aim 1 will use molecular and biochemical techniques to investigate changes in
MCH levels in the OB in response to food restriction. It will also use complementary mouse
models to determine the cellular targets of hypothalamic MCH neurons in olfactory regions. Aim
2 will investigate the effects of MCH on the activity of mitral cells in the olfactory bulb, and how
changes in MCH effect odor threshold detection and cross-habituation in animals that lack
components of the MCH signaling pathway. It will also test how activation of hypothalamic MCH
neurons modulates these behaviors. Using AAV mediated approaches, we will target MCHR1
removal specifically in the OB to isolate its contribution to regulating behavioral changes. Finally,
in Aim 3 we will investigate how disruption of primary cilia, the cellular site of MCHR1
localization, on neurons in the OB impacts an animal's ability to detect and discriminate odors.
Completion of the proposed studies will provide new mechanistic insight into the role of the lateral
hypothalamus in regulating olfactory function. The results from the proposed research will be
important for understanding how changes in satiety or in wakefulness can impact the sense of
smell. It will also provide insight into mechanisms of sensory dysfunction that occur in some
ciliopathy patients. Completion of this project will establish future experiments to address the
molecular mechanisms of MCH modulation in the OB.
Terms: <Ablation><Abscission><Acute><Address><Affect><Animals><Anterior><Area><Assay><Axon><Behavior><Behavioral><Bioassay><Biochemical><Biological Assay><Brain><Brain Nervous System><Brain region><CNS Nervous System><Cell Body><Cell Communication and Signaling><Cell Signaling><Cells><Central Nervous System><Chemicals><Cilia><Connector Neuron><Detection><Dysfunction><Eating><Encephalon><Environment><Excision><Extirpation><Fast-Wave Sleep><Feeding behaviors><Food><Food Deprivation><Food Intake><Food deprivation (experimental)><Functional disorder><Future><Gene Expression><Genes><Genetic><Goals><Grant><Health><Human><Hunger><Hypothalamic structure><Hypothalamus><Image><Immediate-Early Genes><Immunoblotting><Ingestive Behavior><Intercalary Neuron><Intercalated Neurons><Interneurons><Internuncial Cell><Internuncial Neuron><Intracellular Communication and Signaling><Lateral><MCH receptor><MCH1R><MCHR1><MCHR1 gene><Maps><Mediating><Mice><Mice Mammals><Modeling><Modern Man><Molecular><Monitor><Murine><Mus><Mutant Strains Mice><Nasal cavity><Nerve Cells><Nerve Unit><Neural Cell><Neuraxis><Neurocyte><Neurons><Neuropeptides><Neurophysiology - biologic function><Obesity><Odors><Olfaction><Olfactory Epithelium><Olfactory Pathways><Olfactory system><Olfactory tubercle><Organelles><Organism><Paradoxical Sleep><Pathway interactions><Patients><Peptides><Phenotype><Physiologic><Physiological><Physiopathology><Play><Population><Process><QOL><Quality of life><REM Sleep><Receptor Protein><Regulation><Removal><Research><Rhombencephalic Sleep><Role><SLC1><Satiation><Sensory><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Site><Sleep><Sleep Deprivation><Smell><Smell Perception><Surgical Removal><Techniques><Testing><Transmission><Viral><Volatilization><Wakefulness><Western Blotting><Western Immunoblotting><Whole Body Plethysmography><adiposity><behavior outcome><behavior response><behavior test><behavioral outcome><behavioral response><behavioral test><biological signal transduction><cellular targeting><ciliopathy><circadian><corpulence><deficient sleep><deprived of food><design><designing><dreaming sleep><experiment><experimental research><experimental study><experiments><feeding><feeding-related behaviors><food restriction><gene manipulation><genetic manipulation><genetically manipulate><genetically perturb><glutamate signaling><glutamatergic dendrodendritic synapses><glutamatergic signaling><habituation><hormonal signals><hormone signals><hypothalamic><imaging><inadequate sleep><insight><insufficient sleep><living system><melanin-concentrating hormone><melanin-concentrating hormone receptor><melanin-concentrating hormone receptor 1><melanine-concentrating hormone receptor><melanophore-concentrating hormone><melanosome concentrating hormone><mitral cell><mouse model><mouse mutant><murine model><mutant><neural control><neural function><neural regulation><neuromodulation><neuromodulatory><neuronal><neuroregulation><nutrient intake activity><odor discrimination><odor perception><olfactory bulb><olfactory circuitry><olfactory circuits><olfactory nuclei><olfactory perception><olfactory sensory neurons><open field behavior><pathophysiology><pathway><pharmacologic><piriform cortex><protein blotting><rapid eye movement sleep><receptor><resection><response><satiety><sensory mechanism><sensory system><sleep debt><sleep deficiency><sleep deficit><sleep insufficiency><sleep loss><sleep pattern><smell discrimination><social role><transmission process>