scholarly journals Propagation of cortical activity via open-loop intrathalamic architectures: a computational analysis

2019 ◽  
Author(s):  
Jeffrey W. Brown ◽  
Aynaz Taheri ◽  
Robert V. Kenyon ◽  
Tanya Berger-Wolf ◽  
Daniel A. Llano
Keyword(s):  
Closed Loop ◽  
Neural Model ◽  
Signal Propagation ◽  
Open Loop ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Dorsal Thalamus ◽  
In Series ◽  
Intracortical Connectivity

AbstractPropagation of signals across the cerebral cortex is a core component of many cognitive processes and is generally thought to be mediated by direct intracortical connectivity. The thalamus, by contrast, is considered to be devoid of internal connections and organized as a collection of parallel inputs to the cortex. Here, we provide evidence that “open-loop” intrathalamic connections involving the thalamic reticular nucleus (TRN) can support propagation of oscillatory activity across the cortex. Recent studies support the existence of open-loop thalamo-reticulo-thalamic (TC-TRN-TC) synaptic motifs in addition to traditional closed-loop architectures. We hypothesized that open-loop structural modules, when connected in series, might underlie thalamic and, therefore cortical, signal propagation. Using a supercomputing platform to simulate thousands of permutations of a thalamo-reticular-cortical network and allowing select synapses to vary both by class and individually, we evaluated the relative capacities of closed- and open-loop TC-TRN-TC synaptic configurations to support both propagation and oscillation. We observed that 1) signal propagation was best supported in networks possessing strong open-loop TC-TRN-TC connectivity; 2) intrareticular synapses were neither primary substrates of propagation nor oscillation; and 3) heterogeneous synaptic networks supported more robust propagation of oscillation than their homogeneous counterparts. These findings suggest that open-loop heterogeneous intrathalamic architectures complement direct intracortical connectivity to facilitate cortical signal propagation.Significance StatementInteractions between the dorsal thalamus and thalamic reticular nucleus (TRN) are speculated to contribute to phenomena such as arousal, attention, sleep, and seizures. Despite the importance of the TRN, the synaptic microarchitectures forming the basis for dorsal thalamus-TRN interactions are not fully understood. The computational neural model we present incorporates “open-loop” thalamo-reticular-thalamic (TC-TRN-TC) synaptic motifs, which have been experimentally observed. We elucidate how open-loop motifs possess the capacity to shape the propagative properties of signals intrinsic to the thalamus and evaluate the wave dynamics they support relative to closed-loop TC-TRN-TC pathways and intrareticular synaptic connections. Our model also generates predictions regarding how different spatial distributions of reticulothalamic and intrareticular synapses affect these signaling properties.

scholarly journals Open-loop organization of thalamic reticular nucleus and dorsal thalamus: a computational model

2015 ◽  
Vol 114 (4) ◽  
pp. 2353-2367 ◽  
Author(s):  
Adam M. Willis ◽  
Bernard J. Slater ◽  
Ekaterina D. Gribkova ◽  
Daniel A. Llano
Keyword(s):  
Closed Loop ◽  
Open Loop ◽  
Tunable Filter ◽  
Cortical Activation ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Loop Model ◽  
Dependent Manner ◽  
Dorsal Thalamus ◽  
Low Threshold

The thalamic reticular nucleus (TRN) is a shell of GABAergic neurons that surrounds the dorsal thalamus. Previous work has shown that TRN neurons send GABAergic projections to thalamocortical (TC) cells to form reciprocal, closed-loop circuits. This has led to the hypothesis that the TRN is responsible for oscillatory phenomena, such as sleep spindles and absence seizures. However, there is emerging evidence that open-loop circuits are also found between TRN and TC cells. The implications of open-loop configurations are not yet known, particularly when they include time-dependent nonlinearities in TC cells such as low-threshold bursting. We hypothesized that low-threshold bursting in an open-loop circuit could be a mechanism by which the TRN could paradoxically enhance TC activation, and that enhancement would depend on the relative timing of TRN vs. TC cell stimulation. To test this, we modeled small circuits containing TC neurons, TRN neurons, and layer 4 thalamorecipient cells in both open- and closed-loop configurations. We found that open-loop TRN stimulation, rather than universally depressing TC activation, increased cortical output across a broad parameter space, modified the filter properties of TC neurons, and altered the mutual information between input and output in a frequency-dependent and T-type calcium channel-dependent manner. Therefore, an open-loop model of TRN-TC interactions, rather than suppressing transmission through the thalamus, creates a tunable filter whose properties may be modified by outside influences onto the TRN. These simulations make experimentally testable predictions about the potential role for the TRN for flexible enhancement of cortical activation.

Characterizing rare mis-sense variations of CACNA1I identified in a Swedish schizophrenia cohort

2016 ◽  
Vol 33 (S1) ◽  
pp. S182-S183
Author(s):  
J. Pan ◽  
A. Allen ◽  
L. huang ◽  
D. Daez
Keyword(s):  
Calcium Influx ◽  
Association Studies ◽  
Expression System ◽  
Single Copy ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Patient Specific ◽  
Genome Wide Association Studies ◽  
The Impact

CACNA1I (hCaV3.3) encodes the α1 pore-forming subunit of human voltage-gated T-type calcium channels. CaV3.3 is expressed in a limited subset of neurons including GABAergic neurons of the thalamic reticular nucleus (TRN) where they support oscillatory activity essential for sleep spindle generation. CACNA1I is implicated in schizophrenia risk by emerging genetics including genome-wide association studies (PGC, 2014), and exome sequencing of trio samples (Gulsuner et al., 2013). In order to understand the impact of disease-associated sequence variation on the function of CaV3.3, we set out to analyze a complete set of rare mis-sense coding variations in CACNA1I in a Swedish cohort, including 15 variations identified in patients, 20 identified in control subjects, and 23 in both. We established a heterologous expression system of isogenic cell lines, each carrying single-copy inducible cDNA variants of hCaV3.3, and evaluated their functional impact on channel function by electrophysiology, calcium imaging, and biochemistry. We found at least five coding variations impaired overall channel protein abundance, as well as whole cell current density. In addition, we identified hCaV3.3 variants with altered voltage-dependence of channel activation and inactivation. Overall, we found that reduced calcium influx through hCaV3.3 is associated with the group of variants identified in patients, compared to those in both patients and controls. Our findings suggest that patient-specific rare variations of CACNA1I may influence channel-dependent functions, including rebound bursting in TRN neurons, with potential implications for schizophrenia pathophysiology.Disclosure of interestThe authors have not supplied their declaration of competing interest.

scholarly journals Closed-loop Controller Based on Reference Signal Tracking for Absence Seizures

2021 ◽  
Author(s):  
Hudong Zhang ◽  
Yuting Chen ◽  
Yan Xie ◽  
Yuan Chai
Keyword(s):  
Firing Rate ◽  
Closed Loop ◽  
Reference Signal ◽  
Absence Epilepsy ◽  
Open Loop ◽  
Recursive Least Squares ◽  
Biophysical Model ◽  
Reticular Nucleus ◽  
Cortical Region ◽  
Absence Seizures

Abstract Deep brain stimulation (DBS) targeting thalamus reticular nucleus (TRN) brain regions has been proven to play an irreplaceable role in the treatment of absence seizures. Compared with open-loop DBS, closed-loop DBS has been recognized by researchers for its advantages of significantly inhibiting seizures and having fewer side effects. However, due to the complexity of the nervous system, the mechanism of DBS control epilepsy is still unclear, which hinders the study of closed-loop DBS. In our study, based on the biophysical model jointly constituted by cortical, thalamic, and basal ganglia, we selected the 2-4 Hz spike and wave discharges (SWDs) of the cortical region as a biomarker for response to absence epilepsy, and the mean firing rate (MFR) of substantia nigra pars reticulata (SNr) was used as a reference signal for modulation of closed-loop DBS. Moreover, to obtain the linear relationship between the stimulus and the response, we adopted an algorithm that combines controlled auto-regressive (CAR) and recursive least squares (RLS), and we built a proportional integral (PI) controller to make the DBS stimulus parameters self-update to control the seizures. The numerical simulation results show that the closed-loop DBS controllers based on frequency modulation and amplitude modulation respectively not only successfully track the firing rate (FR) of SNr, but also significantly destroy the SWDs of cerebral cortex and restore it to the other two normal discharge modes.

scholarly journals Spindle oscillations are generated in the dorsal thalamus and modulated by the thalamic reticular nucleus

2008 ◽  
Author(s):  
Chun-Hua Liu ◽  
Yi Ping Guo ◽  
Xian-Kai Meng ◽  
Yan-Qin Yu ◽  
Ying Xiong ◽  
...  
Keyword(s):  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Dorsal Thalamus

scholarly journals Functional topographic organization of the motor reticulothalamic pathway

2015 ◽  
Vol 113 (9) ◽  
pp. 3090-3097 ◽  
Author(s):  
Ying-Wan Lam ◽  
S. Murray Sherman
Keyword(s):  
Laser Scanning ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Thalamic Nuclei ◽  
Dorsal Thalamus ◽  
Thalamic Relay ◽  
Thalamocortical Projections ◽  
Motor Information ◽  
Laser Scanning Photostimulation ◽  
Similar Organization

The thalamic reticular nucleus (TRN) is a thin layer of GABAergic cells lying rostral and lateral to the dorsal thalamus, and its projection to thalamic relay cells (i.e., the reticulothalamic pathway) strongly inhibits these cells. In an attempt to extend earlier studies of reticulothalamic connections to sensory thalamic nuclei, we used laser-scanning photostimulation to study the reticulothalamic projections to the main motor thalamic relays, the ventral anterior and lateral (VA and VL) nuclei, as well as to the nearby central lateral (CL) thalamic nucleus. VA/VL and the earlier studied somatosensory thalamic nuclei are considered “core” nuclei with topographic thalamocortical projections, whereas CL is thought to be a “matrix” nucleus with diffuse thalamocortical projections. We found that the TRN input footprints to VA/VL and CL are spatially localized and topographic and generally conform to the patterns established earlier for the TRN projections to sensory thalamic relays. These remarkable similarities suggest similar organization of reticulothalamic pathways and TRN regulation of thalamocortical communication for motor and sensory systems and perhaps also for core and matrix thalamus. Furthermore, we found that VA/VL and CL shared overlapping TRN input regions, suggesting that CL may also be involved in the relay of motor information.

scholarly journals Thalamic circuitry and thalamocortical synchrony

2002 ◽  
Vol 357 (1428) ◽  
pp. 1659-1673 ◽  
Author(s):  
Edward G. Jones
Keyword(s):  
Cortical Neurons ◽  
Low Frequency ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Cortical Cells ◽  
Dorsal Thalamus ◽  
High Frequency Oscillations ◽  
Voltage Dependent ◽  
Layer V ◽  
Layer Vi

The corticothalamic system has an important role in synchronizing the activities of thalamic and cortical neurons. Numerically, its synapses dominate the inputs to relay cells and to the γ–amino butyric acid (GABA)ergic cells of the reticular nucleus (RTN). The capacity of relay neurons to operate in different voltage–dependent functional modes determines that the inputs from the cortex have the capacity directly to excite the relay cells, or indirectly to inhibit them via the RTN, serving to synchronize high– or low–frequency oscillatory activity respectively in the thalamocorticothalamic network. Differences in the α–amino–3–hydroxy–5–methyl–4–isoxazolepropionic acid (AMPA) subunit composition of receptors at synapses formed by branches of the same corticothalamic axon in the RTN and dorsal thalamus are an important element in the capacity of the cortex to synchronize low–frequency oscillations in the network. Interactions of focused corticothalamic axons arising from layer VI cortical cells and diffuse corticothalamic axons arising from layer V cortical cells, with the specifically projecting core relay cells and diffusely projecting matrix cells of the dorsal thalamus, form a substrate for synchronization of widespread populations of cortical and thalamic cells during high–frequency oscillations that underlie discrete conscious events.

scholarly journals Deficient thalamo-cortical networks dynamics and sleep homeostatic processes in a redox dysregulation model relevant to schizophrenia.

2021 ◽  
Author(s):  
Christina Czekus ◽  
Pascal Steullet ◽  
Thomas Rusterholz ◽  
Ivan Bozic ◽  
Kim Do Cuenod ◽  
...  
Keyword(s):  
Recovery Period ◽  
Nrem Sleep ◽  
Sleep Architecture ◽  
Anterior Cingulate ◽  
Thalamic Reticular Nucleus ◽  
Reticular Nucleus ◽  
Glutathione Synthetase ◽  
Cortical Networks ◽  
Dorsal Thalamus ◽  
Sleep Homeostasis

A growing body of evidence implicates thalamo-cortical oscillations with the neuropathophysiology of schizophrenia (SZ) in both mice and humans. Yet, the precise mechanisms underlying sleep perturbations in SZ remain unclear. Here, we characterised the dynamics of thalamo-cortical networks across sleep-wake states in a mouse model carrying a mutation in the enzyme glutathione synthetase gene (Gclm-/-) associated with SZ in humans. We hypothesised that deficits in parvalbumin immunoreactive cells in the thalamic reticular nucleus (TRN) and the anterior cingulate cortex (ACC) -caused by oxidative stress - impact thalamocortical dynamics, thus affecting non-rapid eye movement (NREM) sleep and sleep homeostasis. Using polysomnographic recordings in mice, we showed that KO mice exhibited a fragmented sleep architecture, similar to SZ patients and altered sleep homeostasis responses revealed by an increase in NREM latency and slow wave activities during the recovery period (SR). Although NREM sleep spindle rate during spontaneous sleep was similar in Gclm-/- and Gcml +/+, KO mice lacked a proper homeostatic response during SR. Interestingly, using multisite electrophysiological recordings in freely-moving mice, we found that high order thalamic network dynamics showed increased synchronisation, that was exacerbated during the sleep recovery period subsequent to extended wakefulness (SD), possibly due to lower bursting activity in TRN-antero dorsal thalamus circuit in KO compared to WT littermates. Collectively, these findings provide a mechanism for SZ associated deficits of thalamo-cortical neuron dynamics and perturbations of sleep architecture.

scholarly journals TRPM4 conductances in thalamic reticular nucleus neurons generate persistent firing during slow oscillations

2020 ◽  
Author(s):  
John J. O’Malley ◽  
Frederik Seibt ◽  
Jeannie Chin ◽  
Michael Beierlein
Keyword(s):  
Rhythmic Activity ◽  
Thalamic Reticular Nucleus ◽  
Oscillatory Activity ◽  
Reticular Nucleus ◽  
Plateau Potentials ◽  
Slow Oscillations ◽  
Synaptic Circuits ◽  
Ventrobasal Thalamus ◽  
Persistent Firing

AbstractDuring sleep, neurons in the thalamic reticular nucleus (TRN) participate in distinct types of oscillatory activity. While the reciprocal synaptic circuits between TRN and sensory relay nuclei are known to underlie the generation of sleep spindles, the mechanisms regulating slow (<1 Hz) forms of thalamic oscillations are not well understood. Under in vitro conditions, TRN neurons can generate slow oscillations in a cell-intrinsic manner, with postsynaptic Group 1 metabotropic glutamate receptor (mGluR) activation leading to the generation of plateau potentials mediated by both T-type Ca2+ currents and Ca2+ -activated nonselective cation currents (ICAN). However, the identity of ICAN and the possible contribution of thalamic circuits to slow rhythmic activity remain unclear. Using thalamic slices derived from adult mice of either sex, we recorded slow forms of rhythmic activity in TRN neurons, which were mediated by fast glutamatergic thalamoreticular inputs but did not require postsynaptic mGluR activation. For a significant fraction of TRN neurons, synaptic inputs or brief depolarizing current steps led to long-lasting plateau potentials and persistent firing (PF), and in turn, resulted in sustained synaptic inhibition in postsynaptic relay neurons of the ventrobasal thalamus (VB). Pharmacological approaches indicated that plateau potentials were triggered by Ca2+ influx through T-type Ca2+ channels and mediated by Ca2+ and voltage-dependent transient receptor potential melastatin 4 (TRPM4) channels. Taken together, our results suggest that thalamic circuits can generate slow oscillatory activity, mediated by an interplay of TRN-VB synaptic circuits that generate rhythmicity and TRN cell-intrinsic mechanisms that control PF and oscillation frequency.Significance StatementSlow forms of thalamocortical rhythmic activity are thought to be essential for memory consolidation during sleep and the efficient removal of potentially toxic metabolites. In vivo, thalamic slow oscillations are regulated by strong bidirectional synaptic pathways linking neocortex and thalamus. Therefore, in vitro studies in the isolated thalamus can offer important insights about the ability of individual neurons and local circuits to generate different forms of rhythmic activity. We found that circuits formed by GABAergic neurons in the thalamic reticular nucleus (TRN) and glutamatergic relay neurons in the ventrobasal thalamus generated slow oscillatory activity, which was accompanied by persistent firing in TRN neurons. Our results identify both cell-intrinsic and synaptic mechanisms that mediate slow forms of rhythmic activity in thalamic circuits.

Sign in / Sign up

Export Citation Format

Share Document