A5049100062- Neurotransmitter Receptor Influence on Behavior
- Sleep and Wakefulness Research
- Neuroscience and Neuropharmacology Research
- Sleep and related disorders
- Receptor Mechanisms and Signaling
- Regulation of Appetite and Obesity
- Circadian rhythm and melatonin
- Neural dynamics and brain function
- Memory and Neural Mechanisms
- Nerve injury and regeneration
- Stress Responses and Cortisol
- Neurological disorders and treatments
- Parkinson's Disease Mechanisms and Treatments
- Neuroscience and Neural Engineering
- Neural and Behavioral Psychology Studies
- HIV Research and Treatment
- HIV/AIDS Research and Interventions
- Attention Deficit Hyperactivity Disorder
- HIV-related health complications and treatments
- Neuroendocrine regulation and behavior
- Cannabis and Cannabinoid Research
- Photoreceptor and optogenetics research
- Spinal Cord Injury Research
- Pharmacological Receptor Mechanisms and Effects
- Mind wandering and attention
Drexel University
2015-2024
Pontificia Universidad Católica de Chile
2017
University of Colorado Denver
2017
Wake Forest University
2007-2014
University of Wisconsin–Madison
2000-2008
Beth Israel Deaconess Medical Center
2004-2007
Harvard University
2004-2006
Stanford University
2005
University of Wisconsin System
2003
Abstract Emotions, stress, hunger, and circadian rhythms all promote wakefulness behavioral arousal. Little is known about the pathways mediating these influences, but orexin‐producing neurons of hypothalamus may play an essential role. These cells heavily innervate many wake‐promoting brain regions, mice lacking orexin have narcolepsy fail to rouse in response hunger (Yamanaka et al. [ 2003 ] Neuron 38:701–713). To identify afferents neurons, we first injected a retrograde tracer into...
Clozapine N-oxide (CNO) is a ligand for powerful chemogenetic system that can selectively inhibit or activate neurons; the so-called Designer Receptors Exclusively Activated by Drugs (DREADD) system. This consists of synthetic G-protein-coupled receptors, which are not believed to be activated any endogenous ligand, but otherwise inert CNO. However, it has previously been shown administration CNO in humans and rats leads detectable levels bioactive compounds clozapine N-desmethylclozapine...
<h3>Abstract</h3> In December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, Hubei Province, China. No specific treatment has been established against disease-2019 (COVID-19) so far. Therefore, it is urgently needed to identify effective antiviral agents for the of this disease, and several approved drugs such as lopinavir have evaluated. Here, we report that nelfinavir, an HIV-1 protease inhibitor, potently inhibits replication SARS-CoV-2. The...
Abstract Recent evidence suggests that the hypocretin–orexin system participates in regulation of reinforcement processes. The current studies examined extent to which hypocretin neurotransmission regulates behavioral and neurochemical responses cocaine, food reinforcement. These used a combination fixed ratio, discrete trials, progressive ratio threshold self‐administration procedures assess whether 1 receptor antagonist, SB‐334867, reduces cocaine rats. Progressive sucrose were also...
The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to extracellular levels, or tone, their respective neurotransmitter. Diurnal variation dopamine tone has also been demonstrated within the striatum, but this is unique, likely not related firing; largely because observation midbrain neurons do display diurnal fluctuations rates. Therefore, we conducted a systematic investigation possible mechanisms for tone. Using...
Abstract Social isolation ( SI ) rearing, a model of early life stress, results in profound behavioral alterations, including increased anxiety‐like behavior, impaired sensorimotor gating and self‐administration addictive substances. These changes are accompanied by alterations mesolimbic dopamine function, such as metabolite tissue content, responses to cues psychostimulants, neuron burst firing. Using voltammetric techniques, we examined the effects rearing on transporter activity,...
Ventral tegmental area (VTA) dopamine (DA) neurons perform diverse functions in motivation and cognition, but their precise roles addiction-related behaviors are still debated. Here, we targeted VTA DA for bidirectional chemogenetic modulation during specific tests of cocaine reinforcement, demand, relapse-related male rats, querying the neuron inhibitory excitatory G-protein signaling these processes. Designer receptor stimulation G q signaling, not s enhanced seeking via functionally...
Many neurochemically distinct systems interact to regulate wakefulness and sleep. Wakefulness is promoted by brainstem hypothalamic neurons producing acetylcholine, norepinephrine, dopamine, serotonin, histamine, orexin/hypocretin. Each of these arousal capable increasing wakefulness, but coordinated activity in all pathways required for complete alertness cortical activation. Neurons the pons preoptic area control rapid eye movement non-rapid Mutual inhibition between wake- sleep-regulating...
Abstract Hypocretin/orexin neurons give rise to an extensive projection system, portions of which innervate multiple regions associated with the regulation behavioral state. These include locus coeruleus, medial septal area, preoptic and substantia innominata. Evidence indicates that hypocretin modulates state via actions within each these terminal fields. To understand better circuitry underlying hypocretin‐dependent modulation state, present study characterized degree there exists: 1)...
Study Objective:People with narcolepsy and mice lacking orexin/hypocretin have disrupted sleep/wake behavior reduced physical activity. Our objective was to identify physiologic mechanisms through which orexin deficiency reduces locomotor
Extensive evidence suggests that the hypocretins/orexins influence cocaine reinforcement and dopamine signaling via actions at hypocretin receptor 1. By comparison, involvement of 2 in reward processes has received relatively little attention. Thus, although there is some regulates intake drugs abuse, it currently unclear to what extent participates regulation or self-administration, particularly under high effort conditions. To address this, we examined effects 1, and/or blockade on...
Abstract Orexins (‘hypocretins’) are peptides produced by neurons of the hypothalamus that project to structures implicated in reward and emotion processing. Converging evidence demonstrates functional roles orexin signaling arousal, sleep/wakefulness motivated behaviors for natural drug rewards. Suvorexant, a dual receptor antagonist, recently received approval from US Food Drug Administration treat insomnia. In Experiment 1, rats self‐administered cocaine under progressive‐ratio schedule...
Norepinephrine acts within select basal forebrain regions to modulate behavioral state and/or state-dependent processes, including the general encompassing medial septal area, preoptic and substantia innominata. The present study examined origin organization of noradrenergic efferents these by using combined immunohistochemical identification neurons with retrograde tracing. Results indicate that locus coeruleus provides majority input regions. Lesser, although at times substantial,...
The hypocretins/orexins are comprised of two neuroexcitatory peptides that synthesized exclusively within a circumscribed region the lateral hypothalamus. These project widely throughout brain and interact with variety regions involved in regulation arousal-related processes including those associated motivated behavior. current review focuses on emerging evidence indicating hypocretins influence reward reinforcement processing via actions mesolimbic dopamine system. We discuss contemporary...
The classic motor deficits of Parkinson's disease are caused by degeneration dopaminergic neurons in the substantia nigra pars compacta, resulting loss their long-distance axonal projections that modulate striatum. Current treatments only minimize symptoms this disconnection as there is no approach capable replacing nigrostriatal pathway. We applying microtissue engineering techniques to create living, implantable constructs mimic architecture and function These consist with long tracts...