A5041779895- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Neuroscience and Neural Engineering
- Neurological disorders and treatments
- EEG and Brain-Computer Interfaces
- Receptor Mechanisms and Signaling
- Genetic Neurodegenerative Diseases
- Treatment of Major Depression
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal Respiratory Health Research
- Parkinson's Disease Mechanisms and Treatments
- stochastic dynamics and bifurcation
- Photoreceptor and optogenetics research
- Biochemical Analysis and Sensing Techniques
- Respiratory and Cough-Related Research
- Motor Control and Adaptation
- Cerebrospinal fluid and hydrocephalus
- Inhalation and Respiratory Drug Delivery
- Tryptophan and brain disorders
- Neuroendocrine regulation and behavior
- Fetal and Pediatric Neurological Disorders
- Asthma and respiratory diseases
- Estrogen and related hormone effects
- Stress Responses and Cortisol
Boston University
2015-2024
University of Southern California
2024
The University of Tokyo
2023
University of California, Los Angeles
2007
AstraZeneca (Brazil)
2001
Wilmington University
1988-1991
Enhanced oscillations at beta frequencies (8-30 Hz) are a signature neural dynamic pathology in the basal ganglia and cortex of Parkinson's disease patients. The mechanisms underlying these pathological remain elusive. Here, using mathematical models, we find that robust can emerge from inhibitory interactions between striatal medium spiny neurons. interaction synaptic GABAa currents intrinsic membrane M-current promotes population frequency range. Increased levels cholinergic drive,...
Abstract The glymphatic movement of fluid through the brain removes metabolic waste 1–4 . Noninvasive 40 Hz stimulation promotes neural activity in multiple regions and attenuates pathology mouse models Alzheimer’s disease 5–8 Here we show that multisensory gamma influx cerebrospinal efflux interstitial cortex 5XFAD model disease. Influx was associated with increased aquaporin-4 polarization along astrocytic endfeet dilated meningeal lymphatic vessels. Inhibiting clearance abolished removal...
Propofol, like most general anesthetic drugs, can induce both behavioral and electroencephalographic (EEG) manifestations of excitation, rather than sedation, at low doses. Neuronal excitation is unexpected in the presence this GABA A -potentiating drug. We construct a series network models to understand paradox. Individual neurons have ion channel conductances with Hodgkin–Huxley-type formulations. Propofol increases maximal conductance time constant decay synaptic current. Networks range...
Significance Exaggerated beta oscillations within the cortico-basal ganglia-thalamic (CBT) network are putative electrophysiological signatures of bradykinesia and rigidity in Parkinson’s disease (PD). However, it is unclear how exaggerated emerge such oscillation patterns related to PD motor deficits. In this study, we demonstrate that a single cell type, striatal cholinergic interneuron, mediates emergence CBT circuits normal mice induces parkinsonian-like Because system uninhibited by...
Significance We investigated the therapeutic mechanisms of high-frequency stimulation (HFS) in Parkinson’s disease by developing a computational model cortico-basal ganglia-thalamo-cortical loop normal and parkinsonian conditions under effects at several frequencies. found that injected elicits neural perturbations travel along multiple pathways with different latencies rendezvous striatum (one basal ganglia). If frequency is high enough, these overlap (reinforcement) cause more regular,...
Significance Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is highly effective for treating motor symptoms of Parkinson’s disease (PD). However, neural mechanisms by which DBS acts are unknown. PD tied to altered rhythms basal ganglia (BG) and particularly striatum. We develop a biophysical model BG pathway show how beta oscillations can emerge throughout PD. then establish mechanism STN interrupt these abnormal restore brain’s capability produce regulate normal lost with...
We investigate firing threshold manifolds in a mathematical model of an excitable neuron. The analyzed investigates the phenomenon post-inhibitory rebound spiking due to propofol anesthesia and is adapted from McCarthy et al. (SIAM J. Appl. Dyn. Syst. 11(4):1674–1697, [2012]). Propofol modulates decay time-scale inhibitory GABAa synaptic current. Interestingly, this system gives rise within specific range doses. Using techniques geometric singular perturbation theory, we identify structures,...
The anesthetic propofol elicits many different spectral properties on the EEG, including alpha oscillations (8–12 Hz), Slow Wave Oscillations (SWO, 0.1–1.5 and dose-dependent phase-amplitude coupling (PAC) between SWO. Propofol is known to increase GABAA inhibition decrease H-current strength, but how it generates these rhythms their interactions still unknown. To investigate both generation of rhythm its PAC SWO, we simulate a Hodgkin-Huxley network model hyperpolarized thalamus...
Ketamine is an N-methyl-D-aspartate (NMDA)-receptor antagonist that produces sedation, analgesia, and dissociation at low doses profound unconsciousness with antinociception high doses. At doses, ketamine can generate gamma oscillations (>25 Hz) in the electroencephalogram (EEG). The are interrupted by slow-delta (0.1 to 4 Ketamine’s primary molecular targets its oscillatory dynamics have been characterized. However, how actions of subcellular level give rise observed network remains...
Striatal oscillatory activity is associated with movement, reward, and decision-making, observed in several interacting frequency bands. Local field potential recordings rodent striatum show dopamine- reward-dependent transitions between two states: a "spontaneous" state involving β (∼15-30 Hz) low γ (∼40-60 Hz), θ (∼4-8 high (∼60-100 response to dopaminergic agonism reward. The mechanisms underlying these rhythmic dynamics, their interactions, functional consequences are not well...
Early-life experience enduringly sculpts thalamocortical (TC) axons and sensory processing. Here, we identify the very first synaptic targets that initiate critical period plasticity, heralded by altered cortical oscillations. Monocular deprivation (MD) acutely induced a transient (<3 h) peak in EEG γ-power (~40 Hz) specifically within visual cortex, but only when was open (juvenile mice or adults after dark-rearing, Lynx1 -deletion, diazepam-rescued GAD65-deficiency). Rapid TC input loss...
GABAergic anesthetics induce alpha/low-beta and slow oscillations in the EEG, which interact dose-dependent ways. We constructed a thalamocortical model to investigate how these interdependent change with propofol dose. find two dynamic states of coordination, on timescale seconds dose-dependently mirror known changes EEG. Thalamocortical feedback determines oscillatory coupling power seen each state, this is primarily driven by cortical synchrony brain stem neuromodulation.
Theta (4-8 Hz) and gamma (30-80 rhythms in the brain are commonly associated with memory learning (Kahana J Neurosci 26:1669-1672, 2006; Quilichini et al. 30:11128-11142, 2010). The precision of co-firing between neurons incoming inputs is critical these cognitive functions. We consider an inhibitory neuron model M-current under forcing from pulses a sinusoidal current theta frequency. has long time constant (∼90 ms) it been shown to generate resonance at frequencies (Hutcheon Yarom Trends...
Classical accounts of biased competition require an input bias to resolve the between neuronal ensembles driving downstream processing. However, flexible and reliable selection behaviorally relevant can occur with unbiased stimulation: striatal D1 D2 spiny projection neurons (SPNs) receive balanced cortical input, yet their activity determines choice GO NO-GO pathways in basal ganglia. We here present a corticostriatal model identifying three mechanisms that rely on physiological asymmetries...
The tachykinins, substance P, neurokinin A, and B, have been implicated in many diseases. present study evaluated the pharmacological properties of a novel tachykinin antagonist ZD6021 [3-cyano-N-((2S)-2-(3,4-dichlorophenyl)-4-[4-[2-(methyl-(S)-sulfinyl)-phenyl]piperidino]butyl)-N-methyl-]-napthamide]. affinity (K(i)) for cloned human (NK)1, NK2, NK3 receptors was 0.12 +/- 0.01, 0.64 0.08, 74 13 nM, respectively. Mucin secretion by Chinese hamster ovary cells transfected with NK1 receptor...
The anesthetic propofol potentiates GABAa (inhibitory) receptors in the central nervous system. Paradoxically, low doses of create manifestations excitation rather than sedation. Previous computational modeling work suggests that postinhibitory rebound spiking may be responsible for this paradoxical excitation. In our models, emerges from an interaction between inhibitory current and a slow potassium (M-current). contrast to previous studies spiking, inhibition is not required strong or...
Abstract Cortico‐basal ganglia‐thalamic ( CBT ) β oscillations (15–30 Hz) are elevated in Parkinson's disease and correlated with movement disability. To date, no experimental paradigm outside of loss dopamine has been able to specifically elevate the loop. Here, we show that activation striatal cholinergic receptors selectively increased mouse striatum motor cortex. In individuals showing simultaneous increases both M1, partial directed coherence PDC from M1 (but not reverse direction). did...
The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3–6 Hz), high (~6–12 and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it not understood what role these play supporting Here, we create biophysically detailed model of circuit to show that several classes interneurons (PV, SOM, VIP) can be critically involved producing rhythms; promote formation dedicated...
The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (∼3-6 Hz), high (∼6-12 and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it not understood what role these play supporting Here, we create biophysically detailed model of circuit to show that several classes interneurons (PV+, SOM+, VIP+) can be critically involved producing rhythms; promote formation dedicated...
The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (~3–6 Hz), high (~6–12 and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it not understood what role these play supporting Here, we create biophysically detailed model of circuit to show that several classes interneurons (PV, SOM, VIP) can be critically involved producing rhythms; promote formation dedicated...
Abstract The basolateral amygdala (BLA) is a key site where fear learning takes place through synaptic plasticity. Rodent research shows prominent low theta (∼3-6 Hz), high (∼6-12 and gamma (>30 Hz) rhythms in the BLA local field potential recordings. However, it not understood what role these play supporting Here, we create biophysically detailed model of circuit to show that several classes interneurons (PV, SOM, VIP) can be critically involved producing rhythms; promote formation...
Abstract Ketamine is an NMDA-receptor antagonist that produces sedation, analgesia and dissociation at low doses profound unconsciousness with antinociception high doses. At doses, ketamine can generate gamma oscillations ( > 25 Hz) in the electroencephalogram (EEG). The are interrupted by slow-delta (0.1-4 Ketamine’s primary molecular targets its oscillatory dynamics have been characterized. However, how actions of subcellular level give rise to observed network remains unknown. By...