A5054021194- Sleep and Wakefulness Research
- Neuroscience and Neuropharmacology Research
- Neural dynamics and brain function
- Photoreceptor and optogenetics research
- Circadian rhythm and melatonin
- Sleep and related disorders
- Memory and Neural Mechanisms
- Neuroscience of respiration and sleep
- Olfactory and Sensory Function Studies
- Ion channel regulation and function
- Neurotransmitter Receptor Influence on Behavior
- Neurogenesis and neuroplasticity mechanisms
- Silk-based biomaterials and applications
- EEG and Brain-Computer Interfaces
- Regulation of Appetite and Obesity
- Anesthesia and Sedative Agents
- Cancer-related cognitive impairment studies
- Mechanical Engineering and Vibrations Research
- Epilepsy research and treatment
- Photochromic and Fluorescence Chemistry
VA Boston Healthcare System
2018-2024
Harvard University
2018-2024
Broad Institute
2017
Imperial College London
2015
Histaminergic neurons in the tuberomammilary nucleus (TMN) of hypothalamus form a widely projecting, wake-active network that sustains arousal. Yet most histaminergic contain GABA. Selective siRNA knockdown vesicular GABA transporter (vgat, SLC32A1) produced hyperactive mice with an exceptional amount sustained wakefulness. Ablation vgat gene throughout TMN further sharpened this phenotype. Optogenetic stimulation caudate-putamen and neocortex "histaminergic" axonal projections from evoked...
The thalamic reticular nucleus (TRN) is implicated in schizophrenia pathology. However, it remains unclear whether alterations of TRN activity can account for abnormal electroencephalographic observed patients, namely reduced spindles (10-15 Hz) during sleep and increased delta (0.5-4 gamma-band (30-80 wakefulness. Here, we utilized optogenetic reverse-microdialysis approaches to modulate the major subpopulation GABAergic neurons, which express calcium-binding protein parvalbumin (PV), are...
Optochemistry, an emerging pharmacologic approach in which light is used to selectively activate or deactivate molecules, has the potential alleviate symptoms, cure diseases, and improve quality of life while preventing uncontrolled drug effects. The development in-vivo applications for optochemistry render brain cells photoresponsive without relying on genetic engineering been progressing slowly. nucleus accumbens (NAc) a region regulation slow-wave sleep (SWS) through integration...
Abstract Study Objectives Sleep spindles are abnormal in several neuropsychiatric conditions and have been implicated associated cognitive symptoms. Accordingly, there is growing interest elucidating the pathophysiology behind spindle abnormalities using rodent models of such disorders. However, whether sleep can reliably be detected mouse electroencephalography (EEG) controversial necessitating careful validation detection analysis techniques. Methods Manual procedures were developed...
The ability to rapidly arouse from sleep is important for survival. However, increased arousals in patients with apnea and other disorders prevent restful contribute cognitive, metabolic, physiologic dysfunction [1Durmer J.S. Dinges D.F. Neurocognitive consequences of deprivation.Semin. Neurol. 2005; 25: 117-129Crossref PubMed Scopus (1038) Google Scholar, 2Shamsuzzaman A.S. Gersh B.J. Somers V.K. Obstructive apnea: implications cardiac vascular disease.JAMA. 2003; 290: 1906-1914Crossref...
Poor sleep quality is associated with age-related cognitive decline, and whether reversal of these alterations possible unknown. In this study, we report how deprivation (SD) affects hippocampal representations, patterns, memory in young old mice. After training a hippocampus-dependent object-place recognition (OPR) task, control animals ad libitum, although experimental undergo 5 h SD, followed by recovery sleep. Young controls SD mice exhibit successful OPR memory, whereas are impaired....
Abstract Identification of mechanisms which increase deep sleep could lead to novel treatments promote the restorative effects sleep. Here, we show that knockdown α3 GABA A -receptor subunit from parvalbumin neurons in thalamic reticular nucleus using CRISPR-Cas9 gene editing increased thalamocortical delta (1.5–4 Hz) oscillations are implicated many health-promoting Inhibitory synaptic currents were strongly reduced vitro. Further analysis revealed power long NREM bouts prior NREM-REM...
Zolpidem, a GABAA receptor-positive modulator, is the gold-standard drug for treating insomnia. Zolpidem prolongs IPSCs to decrease sleep latency and increase time, effects that depend on α2 and/or α3 subunit-containing receptors. Compared with natural NREM sleep, zolpidem also decreases EEG power, an effect depends α1 receptors, which may make zolpidem-induced less optimal. In this paper, we investigate whether needs potentiate only particular GABAergic pathways induce without reducing...
Abstract CACNA1I , a schizophrenia risk gene, encodes subtype of voltage-gated T-type calcium channel Ca V 3.3. We previously reported that patient-derived missense de novo mutation (R1346H) impaired 3.3 function. Here, we generated 3.3-RH knock-in animals, along with mice lacking 3.3, to investigate the biological impact R1346H (RH) variation. found RH altered cellular excitability in thalamic reticular nucleus (TRN), where is abundantly expressed. Moreover, produced marked deficits sleep...
Here, we describe a group of basal forebrain (BF) neurons expressing neuronal Per-Arnt-Sim (PAS) domain 1 (Npas1), developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1 + are distinct from well-studied parvalbumin or cholinergic neurons. GAD67-GFP knock-in confirmed that the vast majority GABAergic, with minimal colocalization glutamatergic vGlut1-cre-tdTomato vGlut2-cre-tdTomato mice. The density...
Sleep-wake scoring is a time-consuming, tedious but essential component of clinical and preclinical sleep research. Sleep even more laborious challenging in rodents due to the smaller EEG amplitude differences between states rapid state transitions which necessitate shorter epochs. Although many automated rodent methods exist, they do not perform as well when new datasets, especially those involve changes EEG/EMG profile. Thus, manual by expert scorers remains gold standard. Here we take...
Abstract Introduction Insomnia, characterized by problems falling asleep, less sleep, and a lower quality is more prevalent among individuals with autism spectrum disorders (ASD) compared to typical development. Insomnia in ASD predicts severity of symptoms impacts life, however the mechanisms linking poor sleep are not well understood. Genetic mouse models have been essential understanding ASD. We previously showed that mice deletion exon 21 Shank3 (Shank3ΔC), high confidence gene,...
ABSTRACT Sleep-wake scoring is a time-consuming, tedious but essential component of clinical and pre-clinical sleep research. Sleep even more laborious challenging in rodents due to the smaller EEG amplitude differences between states rapid state transitions which necessitate shorter epochs. Although many automated rodent methods exist, they do not perform as well when new data sets, especially those involve changes EEG/EMG profile. Thus, manual by expert scorers remains gold-standard. Here...
ABSTRACT Here we describe a novel group of basal forebrain (BF) neurons expressing neuronal PAS domain 1 (Npas1), developmental transcription factor linked to neuropsychiatric disorders. Immunohistochemical staining in Npas1-cre-2A-TdTomato mice revealed BF Npas1 + are distinct from well-studied parvalbumin or cholinergic neurons. GAD67-GFP knock-in confirmed that the vast majority GABAergic, with minimal colocalization glutamatergic vGlut1-cre-tdTomato vGlut2-cre-tdTomato mice. The density...
Sleep-spindles are waxing and waning EEG oscillations (10 - 15 Hz), that characteristic of NREM-sleep. generated when GABAergic reticular thalamic nucleus (TRN) neurons release a barrage inhibition onto thalamocortical neurons. This inhibitory is caused by ‘rebound bursting’ the TRN mediated low-threshold ‘T-Type’ Ca channels. CACNA1I encodes CaV3.3 T-type calcium channels its expression enriched in TRN. associated with cognitive deficits schizophrenia (Wamsley et al., 2013). risk gene, de...
The GABAergic neurons of the thalamic reticular nucleus (TRN) are critical in regulating thalamocortical oscillations, particularly waxing and waning 10-15Hz spindle-oscillations non-rapid-eye-movement (NREM) sleep. Spindles important for sleep-dependent memory consolidation impaired neuropsychiatric disorders such as schizophrenia. Thus, there is considerable interest understanding their regulation. TRN receive inhibitory inputs from basal forebrain hypothalamus, acting on GABAA receptors...
Summary Age-related changes in sleep patterns have been linked to cognitive decline. Specifically, increasing age is associated with fragmentation of and wake cycles. However, it remains unknown if improvements architecture can ameliorate cellular deficits. We evaluated how following restriction affected hippocampal representations memory young old mice. After training a hippocampus- dependent object/place recognition task, control animals were allowed ad libitum , while experimental...
Abstract Introduction Neuronal gap-junctions are extensively expressed in mammalian forebrain and suggested to contribute state-regulation thalamocortical network activity. However, the physiological role of on these processes remains poorly understood. Connexin-36 (Cxn36) is highly brain, representing a mechanism for electrical coupling inhibitory neurons. We examined effects global Cnx36 deletion sleep/wake spontaneous evoked EEG Methods recorded vivo EEG/EMG Cxn36KO mice littermate...
Abstract Identification of mechanisms which increase deep sleep could lead to novel treatments promote the restorative effects sleep. Here, knockdown α3 GABA A -receptor subunit from parvalbumin neurons in thalamic reticular nucleus using CRISPR-Cas9 gene editing increased thalamocortical delta oscillations implicated many health-promoting Inhibitory synaptic currents were strongly reduced vitro . Effects most pronounced mouse (light) period. Further analysis identified a deep-sleep state...
Age-related changes in sleep patterns have been linked to cognitive decline. Specifically, increasing age is associated with fragmentation of and wake cycles. However, it remains unknown if improvements architecture can ameliorate cellular deficits. We evaluated how following restriction affected hippocampal representations memory young old mice. After training a hippocampus-dependent object/place recognition task, control animals were allowed ad libitum, while experimental underwent 5 hours...