A5014981127- Neuroscience and Neuropharmacology Research
- Epilepsy research and treatment
- Sleep and Wakefulness Research
- Neuroscience of respiration and sleep
- Circadian rhythm and melatonin
- Photoreceptor and optogenetics research
- EEG and Brain-Computer Interfaces
- Ion channel regulation and function
- Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Sulfur Compounds in Biology
- Mitochondrial Function and Pathology
- Neurogenesis and neuroplasticity mechanisms
- Neuroendocrine regulation and behavior
- Pharmacological Effects and Toxicity Studies
- Metabolism and Genetic Disorders
- Heart Rate Variability and Autonomic Control
- Advanced Chemical Sensor Technologies
- Anesthesia and Neurotoxicity Research
- Neuroinflammation and Neurodegeneration Mechanisms
- Sleep and related disorders
- Genetics and Neurodevelopmental Disorders
- Ion Transport and Channel Regulation
- Stress Responses and Cortisol
- Adenosine and Purinergic Signaling
- Obstructive Sleep Apnea Research
University of Iowa
2016-2025
Carver Bible College
2020-2024
Yeditepe University
2024
University of Michigan
2024
University of Miami
2024
Baylor College of Medicine
2024
GTx (United States)
2023
Brigham and Women's Hospital
2021
Harvard University
2021
Yale University
2008-2020
Light is a prominent stimulus that synchronizes endogenous circadian rhythmicity to environmental light/dark cycles. Nocturnal light elevates mRNA of the <i>Period1</i>(<i>Per1</i>) gene and induces long term state changes, expressed as phase shifts rhythms. The cellular mechanism for<i>Per1</i> elevation light-induced advance in suprachiasmatic nucleus (SCN), process initiated primarily by glutamatergic neurotransmission from retinohypothalamic tract, was examined. Glutamate (GLU)-induced...
There is a long-standing controversy about the role of serotonin in sleep/wake control, with competing theories that it either promotes sleep or causes arousal. Here, we show there marked increase wakefulness when all neurons are genetically deleted mice hemizygous for ePet1-Cre and homozygous floxed Lmx1b ( f/f/p ). However, this only occurs at cool ambient temperatures can be explained by thermoregulatory defect leads to an motor activity generate heat. Because some stimulated CO 2 ,...
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of patients with refractory epilepsy. Defects central control breathing are important contributors to pathophysiology SUDEP, and serotonin (5-HT) system dysfunction may be involved. Here we examined effect 5-HT neurone elimination or reduction on seizure risk seizure-induced mortality. Adult Lmx1b(f/f/p) mice, which lack >99% neurones CNS, littermate controls (Lmx1b(f/f)) were subjected acute induction by maximal electroshock...
Impaired breathing, cardiac function, and arousal during after seizures are important causes of morbidity mortality. Previous work suggests that these changes associated with depressed brainstem function in the ictal post-ictal periods. Lower serotonergic systems postulated to play an role cardiorespiratory seizures, whereas upper other regulate arousal. However, direct demonstration seizure-associated neuronal activity regions has been lacking. Here, we performed multiunit single-unit...
Abstract Focal cortical dysplasia (FCD), a local malformation of development, is the most common cause pharmacoresistant epilepsy associated with life-long neurocognitive impairments. It remains unclear whether neuronal misplacement required for seizure activity. Here we show that dyslamination and white matter heterotopia are not necessary generation in murine model type II FCDs. These experimental FCDs generated by increasing mTOR activity layer 2/3 neurons medial prefrontal cortex...
The circadian clock in the suprachiasmatic nucleus (SCN) of hypothalamus organizes behavioral rhythms, such as sleep–wake cycle, on a near 24-h time base and synchronizes them to environmental day night. Light information is transmitted SCN by direct retinal projections via retinohypothalamic tract (RHT). Both glutamate (Glu) pituitary adenylyl cyclase-activating peptide (PACAP) are localized within RHT. Whereas Glu an established mediator light entrainment, role PACAP unknown. To understand...
Acid-sensing ion channels (ASICs) generate H(+) -gated Na(+) currents that contribute to neuronal function and animal behavior. Like ASIC1, ASIC2 subunits are expressed in the brain multimerize with ASIC1 influence acid-evoked facilitate localization dendritic spines. To better understand how contributes function, we localized protein tested behavioral consequences of gene disruption. For comparison, also studied ASIC1(-/-) mice. was prominently areas high synaptic density, a few exceptions,...
Arousal from sleep in response to CO 2 is a critical protective phenomenon. Dysregulation of -induced arousal contributes morbidity and mortality prevalent diseases, such as obstructive apnea sudden infant death syndrome. Despite the nature this reflex, precise mechanism for unknown. Because major regulator breathing, prevailing theories suggest that activation respiratory chemo- mechano-sensors required arousal. However, populations neurons are not involved regulation breathing also...
Background The growth arrest-specific transcript 5 gene (GAS5) encodes a long noncoding RNA (lncRNA) and hosts number of small nucleolar RNAs (snoRNAs) that have recently been implicated in multiple cellular processes cancer. Here, we investigate the relationship between DNA damage, p53, GAS5 snoRNAs to gain further insight into potential role this locus cell survival oncogenesis both vivo vitro. Methods We used quantitative techniques analyse effect damage on snoRNA expression assess p53...
Hypercapnia-induced arousal from sleep is an important protective mechanism pertinent to a number of diseases. Most notably among these are the sudden infant death syndrome, obstructive apnea and unexpected in epilepsy. Serotonin (5-HT) plays significant role hypercapnia-induced arousal. The 5-HT's this response unknown. Here we sought identify specific 5-HT receptor subtype(s) involved response. Wild-type mice were pretreated with antagonists against subtypes, as well adrenergic,...
Abstract The current diagnostic criteria of the Diagnostic and Statistical Manual Mental Disorders are being challenged by heterogeneity symptom overlap psychiatric disorders. Therefore, a framework toward more etiology-based classification has been initiated US National Institute Health, research domain project. basic neurobiology human disorders is often studied in rodent models. However, differences outcome measurements hamper translation knowledge. Here, we aimed to present translational...
Hydrogen sulfide (H2S) is a toxin affecting the cardiovascular, respiratory, and central nervous systems. Acute H2S exposure associated with high rate of mortality morbidity. The precise pathophysiology H2S-induced death controversial topic; however, inhibition respiratory center in brainstem commonly cited as cause death. There knowledge gap on toxicity toxic mechanisms acute poisoning brainstem, brain region responsible for regulating many reflective vital functions. Serotonin (5-HT),...
We investigated a role for cAMP/protein kinase A (PKA) in light/glutamate (GLU)-stimulated state changes of the mammalian circadian clock suprachiasmatic nucleus (SCN). Nocturnal GLU treatment elevated [cAMP]; however, agonists cAMP/PKA did not mimic effects light/GLU. Coincident activation enhanced GLU-stimulated early night but blocked light/GLU-induced late night, whereas inhibition reversed these effects. These responses are distinct from those mediated by mitogen-activated protein...
Study Objective:Serotonin (5-hydroxytryptamine, 5-HT) neurons are now thought to promote wakefulness. Early experiments using the tryptophan hydroxylase inhibitor para-chlorophenylalanine (PCPA) had led opposite conclusion, that 5-HT causes sleep, but those studies were subsequently contradicted by electrophysiological and behavioral data. Here we tested hypothesis difference in conclusions was due failure of early PCPA control for recently recognized role thermoregulation.
Summary Focal temporal lobe seizures often cause impaired cortical function and loss of consciousness. Recent work suggests that the mechanism for depressed during focal may depend on decreased subcortical cholinergic arousal, which leads to a sleep‐like state slow‐wave activity. To test this hypothesis, we sought directly activate neurons limbic determine effects function. Here used an optogenetic approach selectively stimulate brainstem in pedunculopontine tegmental nucleus induced lightly...
Sudden unexpected death in epilepsy (SUDEP) is the leading cause of patients with refractory epilepsy. SUDEP occurs more commonly during nighttime sleep. The details why at night are not well understood. Understanding sleep might help to better understand all and hasten development preventive strategies. Here we aimed circumstances causing seizures that occur result death. Groups 12 adult male mice were instrumented for EEG, EMG, EKG recording subjected seizure induction via maximal...
Summary Objective Sudden unexpected death in epilepsy ( SUDEP ) is the leading cause of patients with refractory epilepsy. Although mechanisms for are incompletely understood, seizure‐induced respiratory arrest (S‐ IRA has been strongly and consistently implicated. A body evidence indicates that serotonin (5‐ HT ), a modulator breathing, plays critical role . Because 5‐ norepinephrine NE systems interact many biologic processes known to modulate breathing seizures, we hypothesized may play...
Abstract Acute exposure to high concentrations of hydrogen sulfide (H2S) leads sudden death and, if survived, lingering neurological disorders. Clinical signs include seizures, loss consciousness, and dyspnea. The proximate mechanisms underlying H2S-induced acute toxicity have not been clearly elucidated. We investigated electrocerebral, cardiac, respiratory activity during H2S using electroencephalogram (EEG), electrocardiogram, plethysmography. suppressed electrocerebral disrupted...