A5060634869- Neural dynamics and brain function
- Neuroscience and Neuropharmacology Research
- Memory and Neural Mechanisms
- Photoreceptor and optogenetics research
- stochastic dynamics and bifurcation
- Neuroscience and Neural Engineering
- Neuroinflammation and Neurodegeneration Mechanisms
- Ion channel regulation and function
- Receptor Mechanisms and Signaling
- Gene Regulatory Network Analysis
- Advanced Memory and Neural Computing
- Neural Networks and Applications
- EEG and Brain-Computer Interfaces
- Neurobiology and Insect Physiology Research
- Electrochemical Analysis and Applications
- Nonlinear Dynamics and Pattern Formation
- Diet and metabolism studies
- Cell Image Analysis Techniques
- Functional Brain Connectivity Studies
- Sleep and Wakefulness Research
- Target Tracking and Data Fusion in Sensor Networks
- Lipid Membrane Structure and Behavior
- Genetics and Neurodevelopmental Disorders
- Cholesterol and Lipid Metabolism
- Ecosystem dynamics and resilience
University of Toronto
2015-2024
University Health Network
2015-2024
Krembil Research Institute
2016-2024
Brain (Germany)
2023-2024
Krembil Foundation
2020-2024
Ontario Brain Institute
2020-2023
Health Net
2008-2018
Western Research Institute
2002-2015
Toronto Western Hospital
1998-2014
Canada Research Chairs
2013
The M-current ( I M ), comprised of Kv7 channels, is a voltage-activated K + conductance that plays key role in the control cell excitability. In hippocampal principal cells, controls action potential (AP) accommodation and contributes to medium-duration afterhyperpolarization, but interneuron excitability remains unclear. Here, we investigated stratum oriens (SO) interneurons, both from wild-type transgenic mice which green fluorescent protein (GFP) was expressed somatostatin-containing...
A1 Functional advantages of cell-type heterogeneity in neural circuits Tatyana O. Sharpee A2 Mesoscopic modeling propagating waves visual cortex Alain Destexhe A3 Dynamics and biomarkers mental disorders Mitsuo Kawato F1 Precise recruitment spiking output at theta frequencies requires dendritic h-channels multi-compartment models oriens-lacunosum/moleculare hippocampal interneurons Vladislav Sekulić, Frances K. Skinner F2 Kernel methods reconstruction current sources from extracellular...
1. The dynamic clamp was used to create reciprocally inhibitory two-cell circuits from pairs of pharmacologically isolated gastric mill neurons the stomatogastric ganglion crab, Cancer borealis. 2. We this system study how systematic alterations in intrinsic and synaptic parameters affected network behavior. This has previously only been possible purely computational systems. 3. In absence additional hyperpolarization-activated inward current (IH), stable half-center oscillatory behavior not...
Theta oscillations are essential for learning and memory, their generation requires GABAergic interneurons. To better understand how theta is generated, we explored parvalbumin (PV) somatostatin (SOM) interneurons in CA1 stratum oriens/alveus fire during hippocampal investigated synaptic mechanisms underlying behavior. Combining the use of transgenic mice to visually identify PV SOM intact preparation that can generate vitro without cholinergic agonists, performed simultaneous field...
Bursting in inhibitory interneuronal networks: a role for gap-junctional coupling. Much work now emphasizes the concept that networks play critical roles generating synchronized, oscillatory behavior. Experimental has shown functional alone can produce synchronized activity, and theoretical demonstrated how synchrony could occur mutually networks. Even though gap junctions are known to exist between interneurons, their is far from clear. We present mechanism by which bursting be produced...
It is well known that interneurons are heterogeneous in their morphologies, biophysical properties, pharmacological sensitivities and electrophysiological responses, but it unknown how best to understand this diversity. Given critical roles shaping brain output, important try the functionality of computational characteristics. To do this, we focus on specific interneuron subtypes. In particular, has recently been shown long‐term potentiation induced specifically oriens‐lacunosum/moleculare...
The coupling of high frequency oscillations (HFOs; >100 Hz) and theta (3-12 in the CA1 region rats increases during REM sleep, indicating that it may play a role memory processing. However, is unclear whether itself capable providing major contributions to generation HFOs, or if they are strictly driven through input projections. Parvalbumin-positive (PV+) interneurons an essential these due their extensive connections with neighboring pyramidal cells, characteristic fast-spiking. Thus, we...
Abstract Disinhibition is a widespread circuit mechanism for information selection and transfer. In the hippocampus, disinhibition of principal cells provided by interneuron-specific interneurons that express vasoactive intestinal polypeptide (VIP-IS) innervate selectively inhibitory interneurons. By combining optophysiological experiments with computational models, we determined impact synaptic inputs onto network state-dependent recruitment VIP-IS cells. We found fire spikes in response to...
Characterizing theta rhythms in the hippocampus provides a window into understanding memory processing. An inquiry that arises when an animal sustains pathological state is how are affected. In states like epilepsy or Alzheimer's, these change specific ways. Statistically robust changes could serve as potential biomarkers, indicating severity of animal's condition and effectiveness drug. However, this depends on data analyzed. There currently no standard criteria for recognizing dominance...
Perfusion of rat brain slices with low millimole CsCl elicits slow oscillations </=1 Hz in hippocampal CA1 pyramidal neurons. These are GABAA receptor-mediated hyperpolarizations that permit a coherent fire-pause pattern population They can persist without the activation ionotropic glutamate receptors but require adenosine-dependent inhibition transmission. In response to external Cs+, multiple interneurons region display rhythmic discharges correlate The interneuronal arise spontaneously...
Recent experimental literature has revealed that GABAergic interneurons exhibit increased activity prior to seizure onset, alongside additional evidence such is synchronous and may arise abruptly. These findings have led some hypothesize this interneuronal serve a causal role in driving the sudden change brain heralds onset. However, mechanisms predisposing an inhibitory network toward activity, specifically ictogenesis, without permanent inputs system remain unknown. We address question by...
Rodent hippocampal slices of ≤0.5 mm thickness have been widely used as a convenient in vitro model since the 1970s. However, spontaneous population rhythmic activities do not consistently occur this preparation due to limited network connectivity. To overcome limitation, we develop novel slice 1 from adult mouse hippocampus by separating dentate gyrus CA3/CA1 areas but preserving dentate–CA3-CA1 While superfused at 32 or 37°C, thick exhibits robust rhythms 1–4 Hz that originate CA3 area....
Gap junctions allow direct electrical communication between CNS neurons. From theoretical and modeling studies, it is well known that although gap can act to synchronize network output, they also give rise many other dynamic patterns including antiphase phase-locked states. The particular pattern arises depends on cellular, intrinsic properties affect firing frequencies as the strength location of junctions. Interneurons or GABAergic neurons in hippocampus are diverse their cellular...
During slow wave sleep and consummatory behaviors, electroencephalographic recordings from the rodent hippocampus reveal large amplitude potentials called sharp waves. The waves originate CA3 circuitry their generation is correlated with coherent discharges of pyramidal neurons dependent on activities mediated by AMPA glutamate receptors. To model in a relatively hippocampal vitro, we developed thick (1 mm) mouse slices separating dentate gyrus CA2/CA1 areas while keeping functional...
Slow population activities (SPAs) exist in the brain and have frequencies below ∼5 Hz. Despite SPAs being prominent several cortical areas serving many putative functions, their mechanisms are not well understood. We studied a specific type of <i>in vitro</i> GABAergic, inhibition-based SPA exhibited by C57BL/6 murine hippocampus. used multipronged approach consisting experiment, simulation, mathematical analyses to uncover responsible for hippocampal SPAs. Our results show that an emergent...
Hippocampal theta is a 4-12 Hz rhythm associated with episodic memory, and although it has been studied extensively, the cellular mechanisms underlying its generation are unclear. The complex interactions between different interneuron types, such as those oriens-lacunosum-moleculare (OLM) interneurons bistratified cells (BiCs), make their contribution to network rhythms difficult determine experimentally. We created models that tied experimental work at both levels explore how these affect...
Although biophysical details of inhibitory neurons are becoming known, it is challenging to map these onto function. Oriens-lacunosum/moleculare (O-LM) cells in the hippocampus that gate information flow, firing while phase-locked theta rhythms. We build on our existing computational model database O-LM link with place models high-conductance states and modulate inputs at a wide range frequencies. find preferred spiking recruitment high (4–9 Hz) or low (2–5 depending on, respectively,...
Abstract Scientists have observed local field potential theta rhythms (3–12 Hz) in the hippocampus for decades, but understanding mechanisms underlying their generation is complicated by diversity pharmacological and frequency profiles. In addition, interactions with other brain structures oscillatory drives to during distinct states has made it difficult identify hippocampus-specific properties directly involved generation. To overcome this, we develop cellular-based network models using a...
Oscillations in local field potentials (LFPs) are prevalent and contribute to brain function. An understanding of the cellular correlates pathways affecting LFPs is needed, but many overlapping vivo make this difficult achieve. A LFP rhythm hippocampus associated with memory processing spatial navigation θ (3-12 Hz) oscillation. rhythms emerge intrinsically an vitro whole preparation reduced makes it possible assess contribution different cell types generation. We focus on...