Thalamic Relay Neurons Research Articles

Subunit-specific mechanisms of isoflurane-induced acute tonic inhibition in dentate gyrus granule neuron

Prolonged exposure to volatile anesthetics may raise the risk of developing cognitive impairment by acting on gamma-a Aminobutyric acid A receptors (GABAAR). The dentate gyrus plays an important role in the hippocampus and has a high potential for neural plasticity. However, it is unknown whether prolonged anesthesia induces a change in acute phasic or tonic inhibition in dentate gyrus granule cells (DGGCs) by acting on GABAAR. In order to verify the effects of volatile anesthetics on the current in DGGCs, a whole-cell patch was applied to record acute brain slices, and this study indicated that 4 h but not 2 h of isoflurane (ISO) exposure induced significantly larger tonic currents in DGGCs other than hippocampal CA1 pyramidal and thalamic relay neurons. Furthermore, this study demonstrated that the increased tonic current in DGGCs was dependent on the δ subunit-containing GABAARs by using transgenic δ subunit knockout mice. In conclusion, the δ subunit specific GABAAR is the key element that increased acute tonic inhibition in DGGCs of mice after prolonged ISO exposure, which may be one of the mechanisms of ISO neurotoxicity to the developing brain.

Action Sequence Learning Is Impaired in Genetically Modified Mice with the Suppressed GABAergic Transmission from the Thalamic Reticular Nucleus to the Thalamus.

The thalamic reticular nucleus (TRN) is a thin sheet of GABAergic neurons surrounding the thalamus, and it regulates the activity of thalamic relay neurons. The TRN has been reported to be involved in sensory gating, attentional regulation, and some other functions. However, little is known about the contribution of the TRN to sequence learning. In the present study, we examined whether the TRN is involved in reward-based learning of action sequence with no eliciting stimuli (operant conditioning), by analyzing the performance of male and female Avp-Vgat-/- mice (Vgatflox/flox mice crossed to an Avp-Cre driver line) on tasks conducted in an operant box having three levers. Our histological and electrophysiological data demonstrated that in adult Avp-Vgat-/- mice, vesicular GABA transporter (VGAT) was absent in most TRN neurons and the GABAergic transmission from the TRN to the thalamus was largely suppressed. The performance on a task in which mice needed to press an active lever for food reward showed that simple operant learning of lever pressing and learning of win-stay and lose-shift strategies are not affected in Avp-Vgat-/- mice. In contrast, the performance on a task in which mice needed to press three levers in a correct order for food reward showed that learning of the order of lever pressing (action sequence learning) was impaired in Avp-Vgat-/- mice. These results suggest that the TRN plays an important role in action sequence learning.

Healthy and pathological pallidal regulation of thalamic burst versus tonic mode firing: a computational simulation.

The mechanisms by which the basal ganglia influence the pallidal-receiving thalamus remain to be adequately defined. Our prior in vivo recordings in fully alert normal and dystonic rats revealed that normally fast tonic discharging entopeduncular [EP, rodent equivalent of the globus pallidus internus (GPi)] neurons are pathologically slow, highly irregular, and bursty under dystonic conditions. This, in turn, induces pallidal-receiving thalamic movement-related neurons to change from a healthy burst predominant to a pathological tonic-predominant resting firing mode. This study aims to understand the pallidal influence on thalamic firing modes using computational simulations. We inputted various combinations of healthy and pathological (dystonic) in vivo neuronal recordings to the Rubin and Terman's computational model of low threshold spiking pallidothalamic neurons. The input sets consist of representative tonic, burst, irregular tonic and irregular burst inputs collected from EP/GPi in our animal lab. Initial test combinations of EP/ GPi input to the model were identical to the neuronal population distributions observed in vivo. The thalamic neuron model outputted similar firing rate and mode as observed in corresponding in-vivo thalamus. Further influence of each individual patterns was also delineated. By simulating the firing properties of encountered neurons, the basal ganglia output is suggested to critically act as firing mode selector for thalamic motor relay neurons. By selecting and determining the timing and extent of opening of thalamic T-type calcium channels via GABAergic hyperpolarizing input, GPi neurons are in position to precisely orchestrate thalamocortical burst motor signaling.

Suppression of seizure in childhood absence epilepsy using robust control of deep brain stimulation: a simulation study

Deep brain stimulation (DBS) is a promising technique to relieve the symptoms in patients with intractable seizures. Although the DBS therapy for seizure suppression dates back more than 40 years, determining stimulation parameters is a significant challenge to the success of this technique. One solution to this challenge with application in a real DBS system is to design a closed-loop control system to regulate the stimulation intensity using computational models of epilepsy automatically. The main goal of the current study is to develop a robust control technique based on adaptive fuzzy terminal sliding mode control (AFTSMC) for eliminating the oscillatory spiking behavior in childhood absence epilepsy (CAE) dynamical model consisting of cortical, thalamic relay, and reticular nuclei neurons. To this end, the membrane voltage dynamics of the three coupled neurons are considered as a three-input three-output nonlinear state delay system. A fuzzy logic system is developed to estimate the unknown nonlinear dynamics of the current and delayed states of the model embedded in the control input. Chattering-free control input (continuous DBS pulses) without any singularity problem is the superiority of the proposed control method. To guarantee the bounded stability of the closed-loop system in a finite time, the upper bounds of the external disturbance and minimum estimation errors are updated online with adaptive laws without any offline tuning phase. Simulation results are provided to show the robustness of AFTSMC in the presence of uncertainty and external disturbances.

Metabolic modulation of synaptic failure and thalamocortical hypersynchronization with preserved consciousness in Glut1 deficiency.

Individuals with glucose transporter type I deficiency (G1D) habitually experience nutrient-responsive epilepsy associated with decreased brain glucose. However, the mechanistic association between blood glucose concentration and brain excitability in the context of G1D remains to be elucidated. Electroencephalography (EEG) in G1D individuals revealed nutrition time-dependent seizure oscillations often associated with preserved volition despite electrographic generalization and uniform average oscillation duration and periodicity, suggesting increased facilitation of an underlying neural loop circuit. Nonlinear EEG ictal source localization analysis and simultaneous EEG/functional magnetic resonance imaging converged on the thalamus-sensorimotor cortex as one potential circuit, and 18F-deoxyglucose positron emission tomography (18F-DG-PET) illustrated decreased glucose accumulation in this circuit. This pattern, reflected in a decreased thalamic to striatal 18F signal ratio, can aid with the PET imaging diagnosis of the disorder, whereas the absence of noticeable ictal behavioral changes challenges the postulated requirement for normal thalamocortical activity during consciousness. In G1D mice, 18F-DG-PET and mass spectrometry also revealed decreased brain glucose and glycogen, but preserved tricarboxylic acid cycle intermediates, indicating no overall energy metabolism failure. In brain slices from these animals, synaptic inhibition of cortical pyramidal neurons and thalamic relay neurons was decreased, and neuronal disinhibition was mitigated by metabolic sources of carbon; tonic-clonic seizures were also suppressed by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor inhibition. These results pose G1D as a thalamocortical synaptic disinhibition disease associated with increased glucose-dependent neuronal excitability, possibly in relation to reduced glycogen. Together with findings in other metabolic defects, inhibitory neuron dysfunction is emerging as a modulable mechanism of hyperexcitability.

Morphology, physiology and synaptic connectivity of local interneurons in the mouse somatosensory thalamus.

The thalamic reticular nucleus (TRN) neurons, projecting across the external medullary lamina, have long been considered to be the only significant source of inhibition of the somatosensory ventral posterior (VP) nuclei of the thalamus. Here we report for the first time effective local inhibition and disinhibition in the VP. Inhibitory interneurons were found in GAD67–GFP‐expressing mice and studied using in vitro multiple patch clamp. Inhibitory interneurons have expansive bipolar or tripolar morphologies, reach across most of the VP nucleus and display low threshold bursting behaviour. They form triadic and non‐triadic synaptic connections onto thalamocortical relay neurons and other interneurons, mediating feedforward inhibition and disinhibition. Synaptic inputs arrive before those expected from the TRN neurons, suggesting that local inhibition plays an early and significant role in the functioning of the somatosensory thalamus. Key points The physiology and structure of local interneurons in the mouse somatosensory thalamus is described for the first time.Inhibitory interneurons have extensive dendritic arborization providing significant local dendro‐dendritic inhibition in the somatosensory thalamus.Triadic and non‐triadic synaptic connectivity onto thalamic relay neurons and other interneurons provides both local feedforward inhibition and disinhibition.Interneurons of the somatosensory thalamus provide inhibition before the thalamic reticular nucleus, suggesting they play an important role in sensory perception.

Tyrosine hydroxylase containing neurons in the thalamic reticular nucleus of male equids

Here we report the unusual presence of thalamic reticular neurons immunoreactive for tyrosine hydroxylase in equids. The diencephalons of one adult male of four equid species, domestic donkey (Equus africanus asinus), domestic horse (Equus caballus), Cape mountain zebra (Equus zebra zebra) and plains zebra (Equus quagga), were sectioned in a coronal plane with series of sections stained for Nissl substance, myelin, or immunostained for tyrosine hydroxylase, and the calcium-binding proteins parvalbumin, calbindin and calretinin. In all equid species studied the thalamic reticular nucleus was observed as a sheet of neurons surrounding the rostral, lateral and ventral portions of the nuclear mass of the dorsal thalamus. In addition, these thalamic reticular neurons were immunopositive for parvalbumin, but immunonegative for calbindin and calretinin. Moreover, the thalamic reticular neurons in the equids studied were also immunopositive for tyrosine hydroxylase. Throughout the grey matter of the dorsal thalamus a terminal network also immunoreactive for tyrosine hydroxylase was present. Thus, the equid thalamic reticular neurons appear to provide a direct and novel potentially catecholaminergic innervation of the thalamic relay neurons. This finding is discussed in relation to the function of the thalamic reticular nucleus and the possible effect of a potentially novel catecholaminergic pathway on the neural activity of the thalamocortical loop.

Sensory Experience Engages Microglia to Shape Neural Connectivity through a Non-Phagocytic Mechanism

Sensory experience remodels neural circuits in the early postnatal brain through mechanisms that remain to be elucidated. Applying a new method of ultrastructural analysis to the retinogeniculate circuit, we find that visual experience alters the number and structure of synapses between the retina and the thalamus. These changes require vision-dependent transcription of the receptor Fn14 in thalamic relay neurons and the induction of its ligand TWEAK in microglia. Fn14 functions to increase the number of bulbous spine-associated synapses at retinogeniculate connections, likely contributing to the strengthening of the circuit that occurs in response to visual experience. However, at retinogeniculate connections near TWEAK-expressing microglia, TWEAK signals via Fn14 to restrict the number of bulbous spines on relay neurons, leading to the elimination of a subset of connections. Thus, TWEAK and Fn14 represent an intercellular signaling axis through which microglia shape retinogeniculate connectivity in response to sensory experience.

In-Depth Characterization of Layer 5 Output Neurons of the Primary Somatosensory Cortex Innervating the Mouse Dorsal Spinal Cord.

Neuronal circuits of the spinal dorsal horn integrate sensory information from the periphery with inhibitory and facilitating input from higher central nervous system areas. Most previous work focused on projections descending from the hindbrain. Less is known about inputs descending from the cerebral cortex. Here, we identified cholecystokinin (CCK) positive layer 5 pyramidal neurons of the primary somatosensory cortex (CCK + S1-corticospinal tract [CST] neurons) as a major source of input to the spinal dorsal horn. We combined intersectional genetics and virus-mediated gene transfer to characterize CCK+ S1-CST neurons and to define their presynaptic input and postsynaptic target neurons. We found that S1-CST neurons constitute a heterogeneous population that can be subdivided into distinct molecular subgroups. Rabies-based retrograde tracing revealed monosynaptic input from layer 2/3 pyramidal neurons, from parvalbumin positive cortical interneurons, and from thalamic relay neurons in the ventral posterolateral nucleus. Wheat germ agglutinin-based anterograde tracing identified postsynaptic target neurons in dorsal horn laminae III and IV. About 60% of these neurons were inhibitory and about 60% of all spinal target neurons expressed the transcription factor c-Maf. The heterogeneous nature of both S1-CST neurons and their spinal targets suggest complex roles in the fine-tuning of sensory processing.

A model based investigation of the period doubling behavior in human steady-state visual evoked potentials

Objective. This study aims at investigating the potential mechanism of period doubling (PD) (subharmonic generation) in human steady-state visual evoked potentials (SSVEPs) by using a mathematical model. Approach. Robinson’s Corticothalamic Model, which includes three main neuronal populations (cortical, thalamic reticular, and thalamic relay neurons) was employed. SSVEP experiments were simulated using this model and dependence of PD behavior in relation to the values of model parameters was investigated. The feedback loop in the model that is responsible for the generation of subharmonic components was thus identified, and this loop was isolated from the rest of the model and analyzed with a describing function approach. Main Results. It has been found in general, for a wide range of parameter values, that if the excitation frequency or half of it is close to the native oscillation frequency of the system, the native oscillation ceases to exist and oscillations at either the excitation frequency or half of it are observed. This observation is in line with the experimental findings except for some discrepancies which are also discussed. The intrathalamic feedback loop is identified to be the potential source of subharmonic oscillations. When isolated from the rest of the model and simulated by itself, it has been found that this feedback loop can show a resonance phenomenon at the subharmonic frequency. By deriving a set of equations based on the necessary conditions for a resonance phenomenon, a semi-analytical method was developed by which one can predict the existence of subharmonic generation for a given set of parameters and stimulus frequency. Significance. This study is the first model-based investigation of the mechanism of subharmonic oscillations. The proposed semi-analytical method can replace extensive time and memory consuming parameter sweep studies.

Current Controversy: Spikes, Bursts, and Synchrony in Generalized Absence Epilepsy: Unresolved Questions Regarding Thalamocortical Synchrony in Absence Epilepsy.

Absence epilepsy is a disorder of thalamocortical networks. Animal models have provided detailed information regarding the core cellular, synaptic, and network features that contribute to the electroencephalogram spike and wave discharge characteristic of typical absence epilepsy. Understanding of seizure networks and dynamics is a critical step toward improving treatments, yet competing conceptual models have evolved to explain seizure initiation and propagation. Recent studies have questioned 2 key model concepts: (1) T-type Ca2+ channel-dependent burst firing in thalamic relay neurons may not be essential for seizure generation, bringing into question the proposed mechanism for the antiepileptic drug ethosuximide in reducing thalamic bursting and (2) widespread synchronized neural activity may not be a core feature of the seizures, indicating that reductions in synchrony would not be a productive therapeutic goal. In this review, I will discuss these current findings, highlight the innovative approaches that have enabled these insights, and provide a unified framework that incorporates these sometimes-conflicting ideas. Finally, I lay out future work that will be necessary to finally resolve the remaining issues.

The Superior Function of the Subplate in Early Neocortical Development.

During early development the structure and function of the cerebral cortex is critically organized by subplate neurons (SPNs), a mostly transient population of glutamatergic and GABAergic neurons located below the cortical plate. At the molecular and morphological level SPNs represent a rather diverse population of cells expressing a variety of genetic markers and revealing different axonal-dendritic morphologies. Electrophysiologically SPNs are characterized by their rather mature intrinsic membrane properties and firing patterns. They are connected via electrical and chemical synapses to local and remote neurons, e.g., thalamic relay neurons forming the first thalamocortical input to the cerebral cortex. Therefore SPNs are robustly activated at pre- and perinatal stages by the sensory periphery. Although SPNs play pivotal roles in early neocortical activity, development and plasticity, they mostly disappear by programmed cell death during further maturation. On the one hand, SPNs may be selectively vulnerable to hypoxia-ischemia contributing to brain damage, on the other hand there is some evidence that enhanced survival rates or alterations in SPN distribution may contribute to the etiology of neurological or psychiatric disorders. This review aims to give a comprehensive and up-to-date overview on the many functions of SPNs during early physiological and pathophysiological development of the cerebral cortex.

Electrical synapses between inhibitory neurons shape the responses of principal neurons to transient inputs in the thalamus: a modeling study

As multimodal sensory information proceeds to the cortex, it is intercepted and processed by the nuclei of the thalamus. The main source of inhibition within thalamus is the reticular nucleus (TRN), which collects signals both from thalamocortical relay neurons and from thalamocortical feedback. Within the reticular nucleus, neurons are densely interconnected by connexin36-based gap junctions, known as electrical synapses. Electrical synapses have been shown to coordinate neuronal rhythms, including thalamocortical spindle rhythms, but their role in shaping or modulating transient activity is less understood. We constructed a four-cell model of thalamic relay and TRN neurons, and used it to investigate the impact of electrical synapses on closely timed inputs delivered to thalamic relay cells. We show that the electrical synapses of the TRN assist cortical discrimination of these inputs through effects of truncation, delay or inhibition of thalamic spike trains. We expect that these are principles whereby electrical synapses play similar roles in regulating the processing of transient activity in excitatory neurons across the brain.

Thalamic inhibition regulates critical-period plasticity in visual cortex and thalamus

During critical periods of development, experience shapes cortical circuits, resulting in the acquisition of functions used throughout life. The classic example of critical-period plasticity is ocular dominance (OD) plasticity, which optimizes binocular vision but can reduce the responsiveness of the primary visual cortex (V1) to an eye providing low-grade visual input. The onset of the critical period of OD plasticity involves the maturation of inhibitory synapses withinV1, specifically those containing the GABAA receptor α1 subunit. Here we show that thalamic relay neurons in mouse dorsolateral geniculate nucleus (dLGN) also undergo OD plasticity. This process depends on thalamic α1-containing synapses and is required for consolidation of the OD shift in V1 during long-term deprivation. Our findings demonstrate that thalamic inhibitory circuits play a central role in the regulation of the critical period. This has far-reaching consequences for the interpretation of studies investigating the molecular and cellular mechanisms regulating critical periods of brain development.

GABAB receptors suppress burst-firing in reticular thalamic neurons

ABSTRACTBurst-firing in thalamic neurons is known to play a key role in mediating thalamocortical (TC) oscillations that are associated with non-REM sleep and some types of epileptic seizure. Within the TC system the primary output of GABAergic neurons in the reticular thalamic nucleus (RTN) is thought to induce the de-inactivation of T-type calcium channels in thalamic relay (TR) neurons, promoting burst-firing drive to the cortex and the propagation of TC network activity. However, RTN neurons also project back onto other neurons within the RTN. The role of this putative negative feedback upon the RTN itself is less well understood, although is hypothesized to induce de-synchronization of RTN neuron firing leading to the suppression of TC oscillations. Here we tested two hypotheses concerning possible mechanisms underlying TC oscillation modulation. Firstly, we assessed the burst-firing behavior of RTN neurons in response to GABAB receptor activation using acute brain slices. The selective GABAB receptor agonist baclofen was found to induce suppression of burst-firing concurrent with effects on membrane input resistance. Secondly, RTN neurons express CaV3.2 and CaV3.3 T-type calcium channel isoforms known to contribute toward TC burst-firing and we examined the modulation of these channels by GABAB receptor activation. Utilizing exogenously expressed T-type channels we assessed whether GABAB receptor activation could directly alter T-type calcium channel properties. Overall, GABAB receptor activation had only modest effects on CaV3.2 and CaV3.3 isoforms. The only effect that could be predicted to suppress burst-firing was a hyperpolarized shift in the voltage-dependence of inactivation, potentially causing lower channel availability at membrane potentials critical for burst-firing. Conversely, other effects observed such as a hyperpolarized shift in the voltage-dependence of activation of both CaV3.2 and CaV3.3 as well as increased time constant of activation of the CaV3.3 isoform would be expected to enhance burst-firing. Together, we hypothesize that GABAB receptor activation mediates multiple downstream effectors that combined act to suppress burst-firing within the RTN. It appears unlikely that direct GABAB receptor-mediated modulation of T-type calcium channels is the major mechanistic contributor to this suppression.

Bidirectional Control of Generalized Epilepsy Networks via Rapid Real-Time Switching of Firing Mode

Thalamic relay neurons have well-characterized dual firing modes: bursting and tonic spiking. Studies in brain slices have led to a model in which rhythmic synchronized spiking (phasic firing) in a population ofrelay neurons leads to hyper-synchronous oscillatory cortico-thalamo-cortical rhythms that result in absence seizures. This model suggests that blocking thalamocortical phasic firing would treat absence seizures. However, recent invivo studies in anesthetized animals have questioned this simple model. Here we resolve this issue by developing a real-time, mode-switching approach to drive thalamocortical neurons into or out of a phasic firing mode in two freely behaving genetic rodent models of absence epilepsy. Toggling between phasic and tonic firing in thalamocortical neurons launched and aborted absence seizures, respectively. Thus, a synchronous thalamocortical phasic firing state is required for absence seizures, and switching to tonic firing rapidly halts absences. This approach should be useful for modulating other networks that have mode-dependent behaviors.

Tectal-derived interneurons contribute to phasic and tonic inhibition in the visual thalamus.

The release of GABA from local interneurons in the dorsal lateral geniculate nucleus (dLGN-INs) provides inhibitory control during visual processing within the thalamus. It is commonly assumed that this important class of interneurons originates from within the thalamic complex, but we now show that during early postnatal development Sox14/Otx2-expressing precursor cells migrate from the dorsal midbrain to generate dLGN-INs. The unexpected extra-diencephalic origin of dLGN-INs sets them apart from GABAergic neurons of the reticular thalamic nucleus. Using optogenetics we show that at increased firing rates tectal-derived dLGN-INs generate a powerful form of tonic inhibition that regulates the gain of thalamic relay neurons through recruitment of extrasynaptic high-affinity GABAA receptors. Therefore, by revising the conventional view of thalamic interneuron ontogeny we demonstrate how a previously unappreciated mesencephalic population controls thalamic relay neuron excitability.

Cortex dynamically modulates responses of thalamic relay neurons through prolonged circuit-level disinhibition in rat thalamus in vivo.

Cortex actively modulates the responses of thalamic relay neurons through corticothalamic (CT) projections. Here we investigated the temporal precision of CT modulation on sensory responses of relay neurons in rat ventral posterior medial thalamus (VPM) to direction-specific whisker stimuli. CT feedback levels were either augmented by cortical electrical microstimulation or depressed by cortical application of muscimol, a potent agonist of γ-aminobutyric acid A-type (GABAA) receptors. To evaluate the temporal specificity of CT influence, we compared the early (3-10 ms after stimulus onset) and late (10-100 ms) response components of VPM single units to whisker deflections in preferred or nonpreferred directions before and after altering CT feedback levels under urethane anesthesia. The data showed that cortical feedback most strongly affected the late responses of single VPM units to whisker stimulation. That is, cortical stimulation consistently increased the late responses of VPM units in the corresponding (homologous) barreloids to the stimulus direction preferred by neurons in the cortical locus stimulated. However, cortical stimulation could either increase or decrease the early response, depending on whether or not cortical and thalamic loci were tuned to the same direction. Such bidirectional regulation of the early and late VPM responses is consistent with a mechanism of circuit-level disinhibition in vivo. The results support the theory that CT feedback on thalamic sensory responses is mediated by a time-dependent shift of the excitation-inhibition balance in the thalamo-cortico-thalamic loop, such as would occur during sensory feature integration, plasticity, and learning in the awake state.

Cortical Feedback Regulates Feedforward Retinogeniculate Refinement

According to the prevailing view of neural development, sensory pathways develop sequentially in a feedforward manner, whereby each local microcircuit refines and stabilizes before directing the wiringof its downstream target. In the visual system, retinalcircuits are thought to mature first and direct refinement in the thalamus, after which cortical circuits refine with experience-dependent plasticity. Incontrast, we now show that feedback from cortex to thalamus critically regulates refinement of the retinogeniculate projection during a discrete window indevelopment, beginning at postnatal day 20 in mice. Disrupting cortical activity during this window, pharmacologically or chemogenetically, increases the number of retinal ganglion cells innervating each thalamic relay neuron. These results suggest that primary sensory structures develop through the concurrent and interdependent remodeling of subcortical and cortical circuits in response to sensory experience, rather than through a simple feedforward process. Our findings also highlight an unexpected function for the corticothalamic projection.

The Impact of Cortical Lesions on Thalamo-Cortical Network Dynamics after Acute Ischaemic Stroke: A Combined Experimental and Theoretical Study.

The neocortex and thalamus provide a core substrate for perception, cognition, and action, and are interconnected through different direct and indirect pathways that maintain specific dynamics associated with functional states including wakefulness and sleep. It has been shown that a lack of excitation, or enhanced subcortical inhibition, can disrupt this system and drive thalamic nuclei into an attractor state of low-frequency bursting and further entrainment of thalamo-cortical circuits, also called thalamo-cortical dysrhythmia (TCD). The question remains however whether similar TCD-like phenomena can arise with a cortical origin. For instance, in stroke, a cortical lesion could disrupt thalamo-cortical interactions through an attenuation of the excitatory drive onto the thalamus, creating an imbalance between excitation and inhibition that can lead to a state of TCD. Here we tested this hypothesis by comparing the resting-state EEG recordings of acute ischaemic stroke patients (N = 21) with those of healthy, age-matched control-subjects (N = 17). We observed that these patients displayed the hallmarks of TCD: a characteristic downward shift of dominant α-peaks in the EEG power spectra, together with increased power over the lower frequencies (δ and θ-range). Contrary to general observations in TCD, the patients also displayed a broad reduction in β-band activity. In order to explain the genesis of this stroke-induced TCD, we developed a biologically constrained model of a general thalamo-cortical module, allowing us to identify the specific cellular and network mechanisms involved. Our model showed that a lesion in the cortical component leads to sustained cell membrane hyperpolarization in the corresponding thalamic relay neurons, that in turn leads to the de-inactivation of voltage-gated T-type Ca2+-channels, switching neurons from tonic spiking to a pathological bursting regime. This thalamic bursting synchronises activity on a population level through divergent intrathalamic circuits, and entrains thalamo-cortical pathways by means of propagating low-frequency oscillations beyond the restricted region of the lesion. Hence, pathological stroke-induced thalamo-cortical dynamics can be the source of diaschisis, and account for the dissociation between lesion location and non-specific symptoms of stroke such as neuropathic pain and hemispatial neglect.