A5016604588- Neurobiology and Insect Physiology Research
- Biochemical Analysis and Sensing Techniques
- Alzheimer's disease research and treatments
- Neuroscience and Neuropharmacology Research
- Insect Utilization and Effects
- Olfactory and Sensory Function Studies
- Pancreatic function and diabetes
- Dementia and Cognitive Impairment Research
- Vagus Nerve Stimulation Research
- Cholinesterase and Neurodegenerative Diseases
- Neurological Disease Mechanisms and Treatments
- Diabetes Management and Research
- Ion channel regulation and function
- Insect and Arachnid Ecology and Behavior
- Biochemical effects in animals
- Sleep and Wakefulness Research
- Physiological and biochemical adaptations
- Neurological Disorders and Treatments
- Epilepsy research and treatment
- Odor and Emission Control Technologies
- Bipolar Disorder and Treatment
- Computational Drug Discovery Methods
- Neuroinflammation and Neurodegeneration Mechanisms
- Advanced Chemical Sensor Technologies
- Memory and Neural Mechanisms
University of Vermont
2023-2025
Washington University in St. Louis
2015-2023
Allen Institute
2022
University of British Columbia
2018-2022
Hope Center for Neurological Disorders
2015-2017
Marymount University
2010-2013
Candid
2010-2013
American Chemistry Council
2000
Epidemiological studies show that patients with type 2 diabetes (T2DM) and individuals a diabetes-independent elevation in blood glucose have an increased risk for developing dementia, specifically dementia due to Alzheimer's disease (AD). These observations suggest abnormal metabolism likely plays role some aspects of AD pathogenesis, leading us investigate the link between aberrant metabolism, T2DM, murine models. Here, we combined two techniques – clamps vivo microdialysis as means...
Each taste modality is generally encoded by a single, molecularly defined, population of sensory cells. However, salt stimulates multiple pathways in mammals and insects, suggesting more complex code for taste. Here, we examine coding Drosophila. After creating comprehensive molecular map comprised five discrete neuron classes across the fly labellum, find that four are activated salt: two exhibiting characteristics ‘low salt’ cells, ‘high classes. Behaviorally, low attraction depends...
Aerobic glycolysis and lactate production in the brain plays a key role memory, yet of this metabolism cognitive decline associated with Alzheimer's disease (AD) remains poorly understood. Here we examined relationship between cerebral levels memory performance an APP/PS1 mouse model AD, which progressively accumulates amyloid-β. In vivo 1 H-magnetic resonance spectroscopy revealed age-dependent within frontal cortex control mice, whereas remained unaltered mice from 3 to 12 months age....
Hyperinsulinemia is a risk factor for late-onset Alzheimer9s disease (AD). <i>In vitro</i> experiments describe potential connections between insulin, insulin signaling, and amyloid-β (Aβ), but <i>in vivo</i> are needed to validate these relationships under physiological conditions. First, we performed hyperinsulinemic-euglycemic clamps with concurrent hippocampal microdialysis in young, awake, behaving <i>APP<sub>swe</sub></i>/<i>PS1<sub>dE9</sub></i> transgenic mice. Both postprandial...
Alzheimer's disease (AD) is a devastating neurodegenerative disorder characterized by pathological brain lesions and decline in cognitive function. β-Amyloid peptides (Aβ), derived from proteolytic processing of amyloid precursor protein (APP), play central role AD pathogenesis. β-Site APP cleaving enzyme 1 (BACE1), the transmembrane aspartyl protease which initiates Aβ production, axonally transported neurons accumulates dystrophic neurites near cerebral deposits AD. BACE1 modified...
Elevated blood glucose levels, or hyperglycemia, can increase brain excitability and amyloid-β (Aβ) release, offering a mechanistic link between type 2 diabetes Alzheimer's disease (AD). Since the cellular mechanisms governing this relationship are poorly understood, we explored whether ATP-sensitive potassium (KATP) channels, which couple changes in energy availability with excitability, play role AD pathogenesis. First, demonstrate that KATP channel subunits Kir6.2/KCNJ11 SUR1/ABCC8 were...
Chemosensory cells across the body of Drosophila melanogaster evaluate environment to prioritize certain behaviors. Previous mapping gustatory receptor neurons (GRNs) on fly labellum identified a set in L-type sensilla that express Ionotropic Receptor 94e (IR94e), but impact IR94e GRNs behavior remains unclear. We used optogenetics and chemogenetics activate found they drive mild feeding suppression enhance egg laying. In vivo calcium imaging revealed respond strongly amino acids, including...
ABSTRACT Artificial sweeteners are highly sweet, non-nutritive compounds that have become increasingly popular over recent decades despite research suggesting their consumption has unintended consequences. Specifically, there is evidence some of these chemicals interact with bitter taste receptors, implying likely generate complex chemosensory signals. Here, we report the basic sensory characteristics in Drosophila , a common model system used to study impacts diet, and find all noncaloric...
For nearly two decades, in vivo calcium imaging has been an effective method for measuring cellular responses to taste stimuli the fruit fly model organism, Drosophila melanogaster. A key strength of this methodology is its ability record taste-induced neural awake animals without need anesthesia. This approach employs binary expression systems (e.g., Gal4-UAS) express indicator GCaMP specific neurons interest. protocol describes a procedure which flies expressing are mounted with labellum...
Amino acids (AAs) are essential dietary macronutrients that impact an organism's fitness in a concentration-dependent manner, but the mechanisms mediating AA detection to drive consumption less clear. In Drosophila, we identified full repertoire of taste cells and receptors involved feeding initiation towards glutamate-rich mixture, tryptone, using vivo calcium imaging proboscis extension response (PER). We found attraction occurs through sweet cells, whereas aversion is mediated Ionotropic...
ABSTRACT Chemosensory cells across the body of Drosophila melanogaster evaluate environment and play a crucial role in neural circuits that prioritize feeding, mating, or egg laying. Previous mapping gustatory receptor neurons (GRNs) on fly labellum identified set L-type sensilla defined by expression Ionotropic Receptor 94e (IR94e), but impact IR94e GRNs behavior remained unclear. To understand their behavioral output, we used optogenetics chemogenetics to activate found they drive mild...
Abstract Taste is crucial for many innate and learned behaviors. In the fly, taste impacts feeding, oviposition, locomotion, mating, memory formation, to name a few. These diverse roles may necessitate apparent distributed nature of responses across different circuits in fly brain, leading complexity that has hindered attempts deduce unifying principles processing coding. Here, we combine information from whole brain connectome with functional calcium imaging examine neural representation at...
Recently there have been reports of liver and kidney tumors in rodents following long-term exposure to di(isononyl) phthalate (DINP). Mechanistic studies suggested that the were a consequence peroxisomal proliferation, whereas (found only male rats) associated with induction α2u-globulin. Because both proliferation α2u-globulin are considered be non-genotoxic carcinogenic processes, it seemed appropriate investigate genotoxic potential DINP. Additional also conducted on di(isodecyl) (DIDP),...
Abstract The sleep-wake cycle is a master regulator of metabolic and neuronal activity when altered, can have profound effects on health disease. Although consideration given to how fluctuations in blood glucose affect peripheral physiology metabolism, less known about dysregulation impacts the intrinsic cooperation between brain metabolism regulate sleep. To understand effect hyper- hypoglycemia these relationships, we paired biosensors measuring hippocampal interstitial fluid (ISF) levels...
ABSTRACT Hyperexcitability is a defining feature of Alzheimer’s disease (AD), where aberrant neuronal activity both cause and consequence AD. Therefore, identifying novel targets that modulate cellular excitability an important strategy for treating ATP-sensitive potassium (K ATP ) channels are metabolic sensors excitability. Sulfonylureas K channel antagonists traditionally used to combat hyperglycemia in diabetic patients by inhibiting pancreatic channels, thereby stimulating insulin...
Abstract An animal’s sensory percepts are not raw representations of the outside world. Rather, they constructs influenced by many factors including species, past experiences, and internal states. One source perceptual variability that has fascinated researchers for decades is effect losing one modality on performance another 1 . Typically, dysfunction sense been associated with elevated function others, creating a type homeostasis 2 For example, people vision loss have reported to...
ABSTRACT Increased neuronal excitability contributes to amyloid-β (Aβ) production and aggregation in the Alzheimer’s disease (AD) brain. Previous work from our lab demonstrated that hyperglycemia, or elevated blood glucose levels, increased brain Aβ release potentially through inward rectifying, ATP-sensitive potassium (K ATP ) channels. K channels are present on several different cell types help maintain excitatory thresholds throughout sensitive changes metabolic environment, which coupled...
SUMMARY Dietary salt detection and consumption are crucial to maintaining fluid ionic homeostasis. To optimize intake, animals employ salt-dependent activation of multiple taste pathways. Generally, sodium activates attractive cells, but attraction is overridden at high concentrations by cation non-selective aversive cells. In flies, avoidance driven both ‘bitter’ neurons a class glutamatergic ‘high salt’ expressing pickpocket23 (ppk23). Although the cellular basis has been described, many...