Andrea Slézia - Academia.edu (original) (raw)

Papers by Andrea Slézia

Research paper thumbnail of Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

bioRxiv (Cold Spring Harbor Laboratory), Mar 10, 2023

Research paper thumbnail of Corticothalamic 5-9 Hz oscillations are more pro-epileptogenic than sleep spindles in rats

The Journal of Physiology, Jun 19, 2006

Research paper thumbnail of An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

Advanced biosystems, Nov 27, 2018

Research paper thumbnail of Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice

Journal of Visualized Experiments, May 16, 2019

Research paper thumbnail of Contrasting the Functional Properties of GABAergic Axon Terminals with Single and Multiple Synapses in the Thalamus

The Journal of Neuroscience, Nov 12, 2008

Research paper thumbnail of Transparent neural interfaces: challenges and solutions of microengineered multimodal implants designed to measure intact neuronal populations using high-resolution electrophysiology and microscopy simultaneously

Microsystems & Nanoengineering

The aim of this review is to present a comprehensive overview of the feasibility of using transpa... more The aim of this review is to present a comprehensive overview of the feasibility of using transparent neural interfaces in multimodal in vivo experiments on the central nervous system. Multimodal electrophysiological and neuroimaging approaches hold great potential for revealing the anatomical and functional connectivity of neuronal ensembles in the intact brain. Multimodal approaches are less time-consuming and require fewer experimental animals as researchers obtain denser, complex data during the combined experiments. Creating devices that provide high-resolution, artifact-free neural recordings while facilitating the interrogation or stimulation of underlying anatomical features is currently one of the greatest challenges in the field of neuroengineering. There are numerous articles highlighting the trade-offs between the design and development of transparent neural interfaces; however, a comprehensive overview of the efforts in material science and technology has not been repor...

Research paper thumbnail of Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson’s disease

Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by ... more Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early o...

Research paper thumbnail of Two-photon GCaMP6f imaging of infrared neural stimulation evoked calcium signals in mouse cortical neurons in vivo

Scientific Reports, 2021

Infrared neural stimulation is a promising tool for stimulating the brain because it can be used ... more Infrared neural stimulation is a promising tool for stimulating the brain because it can be used to excite with high spatial precision without the need of delivering or inserting any exogenous agent into the tissue. Very few studies have explored its use in the brain, as most investigations have focused on sensory or motor nerve stimulation. Using intravital calcium imaging with the genetically encoded calcium indicator GCaMP6f, here we show that the application of infrared neural stimulation induces intracellular calcium signals in Layer 2/3 neurons in mouse cortex in vivo. The number of neurons exhibiting infrared-induced calcium response as well as the amplitude of those signals are shown to be both increasing with the energy density applied. By studying as well the spatial extent of the stimulation, we show that reproducibility of the stimulation is achieved mainly in the central part of the infrared beam path. Stimulating in vivo at such a degree of precision and without any ex...

Research paper thumbnail of Multimodal Characterization of Neural Networks Using Highly Transparent Electrode Arrays

eneuro, 2018

Transparent and flexible materials are attractive for a wide range of emerging bioelectronic appl... more Transparent and flexible materials are attractive for a wide range of emerging bioelectronic applications. These include neural interfacing devices for both recording and stimulation, where low electrochemical electrode impedance is valuable. Here the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is used to fabricate electrodes that are small enough to allow unencumbered optical access for imaging a large cell population with two-photon (2P) microscopy, yet provide low impedance for simultaneous high quality recordings of neural activityin vivo. To demonstrate this, pathophysiological activity was induced in the mouse cortex using 4-aminopyridine (4AP), and the resulting electrical activity was detected with the PEDOT:PSS-based probe while imaging calcium activity directly below the probe area. The induced calcium activity of the neuronal network as measured by the fluorescence change in the cells correlated well with the electrophysiological...

Research paper thumbnail of In vivo characterization of neurophysiological diversity in the lateral supramammillary nucleus during hippocampal sharp-wave ripples of adult rats

The extent of the networks that control the genesis and modulation of hippocampal sharp-wave ripp... more The extent of the networks that control the genesis and modulation of hippocampal sharp-wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R unchanged according to whether or not they increased their firing during SPW-Rs. We show that lSuM SPW-R-active neurons increase their firing prior SPW-Rs peak power and prior hippocampal pyramidal cell activation. Moreover, lSuM SPW-R-active neurons show increased firing activity during theta and slow oscillations as compared to unchanged-neurons. SPW-R-active neurons are more active during high peak power SPW-Rs, whereas SPW-R-unchanged neurons are more active during long SPW-Rs. These results suggest that a sub-population of lSuM neurons can interact with the h...

Research paper thumbnail of Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice

Journal of Visualized Experiments, 2019

Research paper thumbnail of A bilayered PVA/PLGA-bioresorbable shuttle to improve the implantation of flexible neural probes

Journal of Neural Engineering, 2018

Research paper thumbnail of An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

Advanced Biosystems, 2018

The challenge of treating neurological disorders has motivated the development of implantable dev... more The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug‐delivery systems.

Research paper thumbnail of NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural r... more Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology ...

Research paper thumbnail of A szenzoros információ átvitel szelektív szabályzása magasabbrendű talamikus magvakban = Selective control of sensory transmission in higher order thalamic relays

Research paper thumbnail of Ongoing network state controls the length of sleep spindles via inhibitory activity

Neuron, Jan 18, 2014

Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in... more Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in the thalamus; however, what determines their duration is presently unclear. Here, we measured somatic activity of excitatory thalamocortical (TC) cells together with axonal activity of reciprocally coupled inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle alterations in their firing in vivo. We found that spindles with different durations were paralleled by distinct nRT activity, and nRT firing sharply dropped before the termination of all spindles. Both initial nRT and TC activity was correlated with spindle length, but nRT correlation was more robust. Analysis of spindles evoked by optogenetic activation of nRT showed that spindle probability, but not spindle length, was determined by the strength of the light stimulus. Our data indicate that during natural sleep a dynamically fluctuating thalamocortical network controls the duration of sleep spindles via the ma...

Research paper thumbnail of Magasabbrendű talamikus magvak serkentő és gátló kontrollja= Excitatory and inhibitory control of higher order thalamic nuclei

Research paper thumbnail of Corticothalamic 5–9 Hz oscillations are more pro‐epileptogenic than sleep spindles in rats

The Journal of Physiology, 2006

Absence‐related spike‐and‐wave discharges (SWDs) occur in the thalamocortical system during quiet... more Absence‐related spike‐and‐wave discharges (SWDs) occur in the thalamocortical system during quiet wakefulness or drowsiness. In feline generalized penicillin epilepsy, SWDs develop from sleep spindles. In contrast, in genetic absence epilepsy rats from Strasbourg (GAERS), SWDs develop from wake‐related 5–9 Hz oscillations, which are distinct from spindle oscillations (7–15 Hz). Since these two oscillation types share common frequency bands and may contribute to SWD genesis, it is important to compare their thalamic cellular mechanisms. Under neuroleptic analgesia, in GAERS and control non‐epileptic rats barbiturates abolished both SWDs and 5–9 Hz oscillations but increased the incidence of spindle‐like oscillations. Within the thalamocortical circuit 5–9 Hz oscillations occurred more coherently than spindle‐like oscillations. Intracellular events associated with 5–9 Hz and spindle‐like oscillations were distinctively different in both thalamic relay and reticular neurons. In both ce...

Research paper thumbnail of Contrasting the Functional Properties of GABAergic Axon Terminals with Single and Multiple Synapses in the Thalamus

The Journal of Neuroscience, 2008

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct in... more Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one “extrareticular” input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The...

Research paper thumbnail of Phasic, Nonsynaptic GABA-A Receptor-Mediated Inhibition Entrains Thalamocortical Oscillations

The Journal of Neuroscience, 2014

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating ph... more GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs.In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically dur...

Research paper thumbnail of Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson's disease

bioRxiv (Cold Spring Harbor Laboratory), Mar 10, 2023

Research paper thumbnail of Corticothalamic 5-9 Hz oscillations are more pro-epileptogenic than sleep spindles in rats

The Journal of Physiology, Jun 19, 2006

Research paper thumbnail of An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

Advanced biosystems, Nov 27, 2018

Research paper thumbnail of Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice

Journal of Visualized Experiments, May 16, 2019

Research paper thumbnail of Contrasting the Functional Properties of GABAergic Axon Terminals with Single and Multiple Synapses in the Thalamus

The Journal of Neuroscience, Nov 12, 2008

Research paper thumbnail of Transparent neural interfaces: challenges and solutions of microengineered multimodal implants designed to measure intact neuronal populations using high-resolution electrophysiology and microscopy simultaneously

Microsystems & Nanoengineering

The aim of this review is to present a comprehensive overview of the feasibility of using transpa... more The aim of this review is to present a comprehensive overview of the feasibility of using transparent neural interfaces in multimodal in vivo experiments on the central nervous system. Multimodal electrophysiological and neuroimaging approaches hold great potential for revealing the anatomical and functional connectivity of neuronal ensembles in the intact brain. Multimodal approaches are less time-consuming and require fewer experimental animals as researchers obtain denser, complex data during the combined experiments. Creating devices that provide high-resolution, artifact-free neural recordings while facilitating the interrogation or stimulation of underlying anatomical features is currently one of the greatest challenges in the field of neuroengineering. There are numerous articles highlighting the trade-offs between the design and development of transparent neural interfaces; however, a comprehensive overview of the efforts in material science and technology has not been repor...

Research paper thumbnail of Behavioral, neural and ultrastructural alterations in a graded-dose 6-OHDA mouse model of early-stage Parkinson’s disease

Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by ... more Studying animal models furthers our understanding of Parkinson’s disease (PD) pathophysiology by providing tools to investigate detailed molecular, cellular and circuit functions. Different versions of the neurotoxin-based 6-hydroxydopamine (6-OHDA) model of PD have been widely used in rats. However, these models typically assess the result of extensive and definitive dopaminergic lesions that reflect a late stage of PD, leading to a paucity of studies and a consequential gap of knowledge regarding initial stages, in which early interventions would be possible. Additionally, the better availability of genetic tools increasingly shifts the focus of research from rats to mice, but few mouse PD models are available yet. To address these, we characterize here the behavioral, neuronal and ultrastructural features of a graded-dose unilateral, single-injection, striatal 6-OHDA model in mice, focusing on early-stage changes within the first two weeks of lesion induction. We observed early o...

Research paper thumbnail of Two-photon GCaMP6f imaging of infrared neural stimulation evoked calcium signals in mouse cortical neurons in vivo

Scientific Reports, 2021

Infrared neural stimulation is a promising tool for stimulating the brain because it can be used ... more Infrared neural stimulation is a promising tool for stimulating the brain because it can be used to excite with high spatial precision without the need of delivering or inserting any exogenous agent into the tissue. Very few studies have explored its use in the brain, as most investigations have focused on sensory or motor nerve stimulation. Using intravital calcium imaging with the genetically encoded calcium indicator GCaMP6f, here we show that the application of infrared neural stimulation induces intracellular calcium signals in Layer 2/3 neurons in mouse cortex in vivo. The number of neurons exhibiting infrared-induced calcium response as well as the amplitude of those signals are shown to be both increasing with the energy density applied. By studying as well the spatial extent of the stimulation, we show that reproducibility of the stimulation is achieved mainly in the central part of the infrared beam path. Stimulating in vivo at such a degree of precision and without any ex...

Research paper thumbnail of Multimodal Characterization of Neural Networks Using Highly Transparent Electrode Arrays

eneuro, 2018

Transparent and flexible materials are attractive for a wide range of emerging bioelectronic appl... more Transparent and flexible materials are attractive for a wide range of emerging bioelectronic applications. These include neural interfacing devices for both recording and stimulation, where low electrochemical electrode impedance is valuable. Here the conducting polymer poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) is used to fabricate electrodes that are small enough to allow unencumbered optical access for imaging a large cell population with two-photon (2P) microscopy, yet provide low impedance for simultaneous high quality recordings of neural activityin vivo. To demonstrate this, pathophysiological activity was induced in the mouse cortex using 4-aminopyridine (4AP), and the resulting electrical activity was detected with the PEDOT:PSS-based probe while imaging calcium activity directly below the probe area. The induced calcium activity of the neuronal network as measured by the fluorescence change in the cells correlated well with the electrophysiological...

Research paper thumbnail of In vivo characterization of neurophysiological diversity in the lateral supramammillary nucleus during hippocampal sharp-wave ripples of adult rats

The extent of the networks that control the genesis and modulation of hippocampal sharp-wave ripp... more The extent of the networks that control the genesis and modulation of hippocampal sharp-wave ripples (SPW-Rs), which are involved in memory consolidation, remains incompletely understood. Here, we performed a detailed in vivo analysis of single cell firing in the lateral supramammillary nucleus (lSuM) during theta and slow oscillations, including SPW-Rs, in anesthetized rats. We classified neurons as SPW-R-active and SPW-R unchanged according to whether or not they increased their firing during SPW-Rs. We show that lSuM SPW-R-active neurons increase their firing prior SPW-Rs peak power and prior hippocampal pyramidal cell activation. Moreover, lSuM SPW-R-active neurons show increased firing activity during theta and slow oscillations as compared to unchanged-neurons. SPW-R-active neurons are more active during high peak power SPW-Rs, whereas SPW-R-unchanged neurons are more active during long SPW-Rs. These results suggest that a sub-population of lSuM neurons can interact with the h...

Research paper thumbnail of Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice

Journal of Visualized Experiments, 2019

Research paper thumbnail of A bilayered PVA/PLGA-bioresorbable shuttle to improve the implantation of flexible neural probes

Journal of Neural Engineering, 2018

Research paper thumbnail of An Electrocorticography Device with an Integrated Microfluidic Ion Pump for Simultaneous Neural Recording and Electrophoretic Drug Delivery In Vivo

Advanced Biosystems, 2018

The challenge of treating neurological disorders has motivated the development of implantable dev... more The challenge of treating neurological disorders has motivated the development of implantable devices that can deliver treatment when and where it is needed. This study presents a novel brain implant capable of electrophoretically delivering drugs and recording local neural activity on the surface of the brain. The drug delivery is made possible by the integration of a microfluidic ion pump (µFIP) into a conformable electrocorticography (ECoG) device with recording cites embedded next to the drug delivery outlets. The µFIP ECoG device can deliver a high capacity of several biologically important cationic species on demand. The therapeutic potential of the device is demonstrated by using it to deliver neurotransmitters in a rodent model while simultaneously recording local neural activity. These developments represent a significant step forward for cortical drug‐delivery systems.

Research paper thumbnail of NeuroRoots, a bio-inspired, seamless Brain Machine Interface device for long-term recording

Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural r... more Minimally invasive electrodes of cellular scale that approach a bio-integrative level of neural recording could enable the development of scalable brain machine interfaces that stably interface with the same neural populations over long period of time.In this paper, we designed and created NeuroRoots, a bio-mimetic multi-channel implant sharing similar dimension (10µm wide, 1.5µm thick), mechanical flexibility and spatial distribution as axon bundles in the brain. A simple approach of delivery is reported based on the assembly and controllable immobilization of the electrode onto a 35µm microwire shuttle by using capillarity and surface-tension in aqueous solution. Once implanted into targeted regions of the brain, the microwire was retracted leaving NeuroRoots in the biological tissue with minimal surgical footprint and perturbation of existing neural architectures within the tissue. NeuroRoots was implanted using a platform compatible with commercially available electrophysiology ...

Research paper thumbnail of A szenzoros információ átvitel szelektív szabályzása magasabbrendű talamikus magvakban = Selective control of sensory transmission in higher order thalamic relays

Research paper thumbnail of Ongoing network state controls the length of sleep spindles via inhibitory activity

Neuron, Jan 18, 2014

Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in... more Sleep spindles are major transient oscillations of the mammalian brain. Spindles are generated in the thalamus; however, what determines their duration is presently unclear. Here, we measured somatic activity of excitatory thalamocortical (TC) cells together with axonal activity of reciprocally coupled inhibitory reticular thalamic cells (nRTs) and quantified cycle-by-cycle alterations in their firing in vivo. We found that spindles with different durations were paralleled by distinct nRT activity, and nRT firing sharply dropped before the termination of all spindles. Both initial nRT and TC activity was correlated with spindle length, but nRT correlation was more robust. Analysis of spindles evoked by optogenetic activation of nRT showed that spindle probability, but not spindle length, was determined by the strength of the light stimulus. Our data indicate that during natural sleep a dynamically fluctuating thalamocortical network controls the duration of sleep spindles via the ma...

Research paper thumbnail of Magasabbrendű talamikus magvak serkentő és gátló kontrollja= Excitatory and inhibitory control of higher order thalamic nuclei

Research paper thumbnail of Corticothalamic 5–9 Hz oscillations are more pro‐epileptogenic than sleep spindles in rats

The Journal of Physiology, 2006

Absence‐related spike‐and‐wave discharges (SWDs) occur in the thalamocortical system during quiet... more Absence‐related spike‐and‐wave discharges (SWDs) occur in the thalamocortical system during quiet wakefulness or drowsiness. In feline generalized penicillin epilepsy, SWDs develop from sleep spindles. In contrast, in genetic absence epilepsy rats from Strasbourg (GAERS), SWDs develop from wake‐related 5–9 Hz oscillations, which are distinct from spindle oscillations (7–15 Hz). Since these two oscillation types share common frequency bands and may contribute to SWD genesis, it is important to compare their thalamic cellular mechanisms. Under neuroleptic analgesia, in GAERS and control non‐epileptic rats barbiturates abolished both SWDs and 5–9 Hz oscillations but increased the incidence of spindle‐like oscillations. Within the thalamocortical circuit 5–9 Hz oscillations occurred more coherently than spindle‐like oscillations. Intracellular events associated with 5–9 Hz and spindle‐like oscillations were distinctively different in both thalamic relay and reticular neurons. In both ce...

Research paper thumbnail of Contrasting the Functional Properties of GABAergic Axon Terminals with Single and Multiple Synapses in the Thalamus

The Journal of Neuroscience, 2008

Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct in... more Diverse sources of GABAergic inhibition are a major feature of cortical networks, but distinct inhibitory input systems have not been systematically characterized in the thalamus. Here, we contrasted the properties of two independent GABAergic pathways in the posterior thalamic nucleus of rat, one input from the reticular thalamic nucleus (nRT), and one “extrareticular” input from the anterior pretectal nucleus (APT). The vast majority of nRT-thalamic terminals formed single synapses per postsynaptic target and innervated thin distal dendrites of relay cells. In contrast, single APT-thalamic terminals formed synaptic contacts exclusively via multiple, closely spaced synapses on thick relay cell dendrites. Quantal analysis demonstrated that the two inputs displayed comparable quantal amplitudes, release probabilities, and multiple release sites. The morphological and physiological data together indicated multiple, single-site contacts for nRT and multisite contacts for APT axons. The...

Research paper thumbnail of Phasic, Nonsynaptic GABA-A Receptor-Mediated Inhibition Entrains Thalamocortical Oscillations

The Journal of Neuroscience, 2014

GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating ph... more GABA-A receptors (GABA-ARs) are typically expressed at synaptic or nonsynaptic sites mediating phasic and tonic inhibition, respectively. These two forms of inhibition conjointly control various network oscillations. To disentangle their roles in thalamocortical rhythms, we focally deleted synaptic, γ2 subunit-containing GABA-ARs in the thalamus using viral intervention in mice. After successful removal of γ2 subunit clusters, spontaneous and evoked GABAergic synaptic currents disappeared in thalamocortical cells when the presynaptic, reticular thalamic (nRT) neurons fired in tonic mode. However, when nRT cells fired in burst mode, slow phasic GABA-AR-mediated events persisted, indicating a dynamic, burst-specific recruitment of nonsynaptic GABA-ARs.In vivo, removal of synaptic GABA-ARs reduced the firing of individual thalamocortical cells but did not abolish slow oscillations or sleep spindles. We conclude that nonsynaptic GABA-ARs are recruited in a phasic manner specifically dur...