scholarly journals Thalamic reticular control of local sleep in mouse sensory cortex

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Laura MJ Fernandez ◽  
Gil Vantomme ◽  
Alejandro Osorio-Forero ◽  
Romain Cardis ◽  
Elidie Béard ◽  
...  

Sleep affects brain activity globally, but many cortical sleep waves are spatially confined. Local rhythms serve cortical area-specific sleep needs and functions; however, mechanisms controlling locality are unclear. We identify the thalamic reticular nucleus (TRN) as a source for local, sensory-cortex-specific non-rapid-eye-movement sleep (NREMS) in mouse. Neurons in optogenetically identified sensory TRN sectors showed stronger repetitive burst discharge compared to non-sensory TRN cells due to higher activity of the low-threshold Ca2+ channel CaV3.3. Major NREMS rhythms in sensory but not non-sensory cortical areas were regulated in a CaV3.3-dependent manner. In particular, NREMS in somatosensory cortex was enriched in fast spindles, but switched to delta wave-dominated sleep when CaV3.3 channels were genetically eliminated or somatosensory TRN cells chemogenetically hyperpolarized. Our data indicate a previously unrecognized heterogeneity in a powerful forebrain oscillator that contributes to sensory-cortex-specific and dually regulated NREMS, enabling local sleep regulation according to use- and experience-dependence.

2015 ◽  
Vol 114 (4) ◽  
pp. 2353-2367 ◽  
Author(s):  
Adam M. Willis ◽  
Bernard J. Slater ◽  
Ekaterina D. Gribkova ◽  
Daniel A. Llano

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.


2007 ◽  
Vol 24 (6) ◽  
pp. 857-874 ◽  
Author(s):  
THOMAS FITZGIBBON ◽  
BRETT A. SZMAJDA ◽  
PAUL R. MARTIN

The thalamic reticular nucleus (TRN) supplies an important inhibitory input to the dorsal thalamus. Previous studies in non-primate mammals have suggested that the visual sector of the TRN has a lateral division, which has connections with first-order (primary) sensory thalamic and cortical areas, and a medial division, which has connections with higher-order (association) thalamic and cortical areas. However, the question whether the primate TRN is segregated in the same manner is controversial. Here, we investigated the connections of the TRN in a New World primate, the marmoset (Callithrix jacchus). The topography of labeled cells and terminals was analyzed following iontophoretic injections of tracers into the primary visual cortex (V1) or the dorsal lateral geniculate nucleus (LGNd). The results show that rostroventral TRN, adjacent to the LGNd, is primarily connected with primary visual areas, while the most caudal parts of the TRN are associated with higher order visual thalamic areas. A small region of the TRN near the caudal pole of the LGNd (foveal representation) contains connections where first (lateral TRN) and higher order visual areas (medial TRN) overlap. Reciprocal connections between LGNd and TRN are topographically organized, so that a series of rostrocaudal injections within the LGNd labeled cells and terminals in the TRN in a pattern shaped like rostrocaudal overlapping “fish scales.” We propose that the dorsal areas of the TRN, adjacent to the top of the LGNd, represent the lower visual field (connected with medial LGNd), and the more ventral parts of the TRN contain a map representing the upper visual field (connected with lateral LGNd).


2019 ◽  
Vol 13 ◽  
Author(s):  
Gil Vantomme ◽  
Alejandro Osorio-Forero ◽  
Anita Lüthi ◽  
Laura M. J. Fernandez

1986 ◽  
Vol 56 (5) ◽  
pp. 1310-1320 ◽  
Author(s):  
Y. Kayama ◽  
I. Sumitomo ◽  
T. Ogawa

In rats anesthetized with urethan, neuronal activity was recorded in those portions of the thalamic reticular nucleus (TR) excitable by visual, somatosensory, or auditory input. Observations were made on changes in rate and pattern of discharge of these neurons during repetitive stimulation of the laterodorsal tegmental nucleus (LDT), which is composed of cholinergic neurons projecting to the thalamus. In general, TR neurons showed spontaneous activity consisting of sporadic bursts of several spikes and responded to sensory stimulation with bursts of spikes which repeated several times. Weak LDT stimulation depressed or eliminated the occurrence of both spontaneous and evoked burst discharges. When LDT stimulation was sufficiently strong, however, the majority of TR neurons resumed their tonic discharges. In some animals the cortical EEG was recorded simultaneously with unit recording in TR. Suppression of burst discharges in TR was obtained even with LDT stimulation weaker than the threshold for desynchronizing the EEG. The induction of tonic discharge, on the other hand, required stimulation strong enough to produce desynchronization. The effects of LDT stimulation, such as the suppression of bursts and the induction of tonic discharge, were mimicked by acetylcholine and were antagonized by scopolamine, both drugs being applied ionophoretically. Cooling of the visual cortex abolished LDT-induced tonic discharges of visual TR neurons. A recent report and our preliminary observation show that, when the resting potential is relatively hyperpolarized, TR neurons generated a burst of spikes superposed on a low-threshold broad spike, which is inactivated and replaced with tonic firing by depolarization. Supported by these facts, the present results suggest that cholinergic input depolarizes TR neurons directly and that further depolarization occurs indirectly via activated cortex when the LDT stimulation is sufficiently strong to desynchronize EEG.


1998 ◽  
Vol 79 (6) ◽  
pp. 2911-2918 ◽  
Author(s):  
Franck Debarbieux ◽  
Jennifer Brunton ◽  
Serge Charpak

Debarbieux, Franck, Jennifer Brunton, and Serge Charpak. Effect of bicuculline on thalamic activity: a direct blockade of I AHP in reticularis neurons. J. Neurophysiol. 79: 2911–2918, 1998. The thalamic reticular nucleus (RTN) is the major source of inhibitory contacts in the thalamus and thus plays an important role in regulating the excitability of the thalamocortical network. Inhibition occurs through GABAergic synapses on relay cells as well as through GABAergic synapses between reticularis neurons themselves. Here we report that the role and mechanisms of this inhibition, which frequently have been studied using N-methyl derivatives of the γ-aminobutyric acid-A (GABAA) receptor antagonist bicuculline, should be revisited. Using the whole cell patch-clamp technique in thalamic slices from young rats, we observed an enhancement by bicuculline methiodide, methobromide, and methochloride (collectively referred to as bicuculline-M; 5–60 μM) of the low-threshold calcium spike burst in RTN neurons that persisted in the presence of tetrodotoxin (1 μM) and was not reproduced in picrotoxin (100–300 μM). The effect did not involve activation of any GABA receptor subtype. Voltage-clamp recordings showed that bicuculline-M blocked the current underlying the low-threshold spike burst afterhyperpolarization (AHP), an effect that was mimicked by apamin (100 nM). Recordings from nucleated patches extracted from reticularis neurons demonstrated that this effect was not mediated by modulation of the release of an unidentified neurotransmitter but that bicuculline-M directly blocks small conductance (SK) channels. The AHP-blocking effect also was observed in other brain regions, demonstrating that although bicuculline-M is a potent GABAA receptor antagonist, it is of limited value in assessing GABAergic network interactions, which should be studied using picrotoxin or bicuculline-free base. However, bicuculline-M may provide a useful tool for developing nonpeptide antagonists of SK channels.


2018 ◽  
Author(s):  
Jorge Jaramillo ◽  
Jorge F. Mejias ◽  
Xiao-Jing Wang

AbstractComputational modeling of brain mechanisms of cognition has been largely focused on the cortex, but recent experiments have shown that higher-order nuclei of the thalamus, in particular the pulvinar, participate in major cognitive functions and are implicated in psychiatric disorders. Here we show that a pulvino-cortical circuit model, composed of two cortical areas and the pulvinar, captures a range of physiological and behavioral observations related to the macaque pulvinar. Effective connections between the two cortical areas are gated by the pulvinar, allowing the pulvinar to shift the operation regime of these areas during attentional processing and working memory, as well as to resolve decision-making conflict. Furthermore, cortico-pulvinar projections that engage the thalamic reticular nucleus enable the pulvinar to estimate decision-making confidence. Finally, feedforward and feedback pulvino-cortical pathways participate in frequency-dependent inter-areal interactions that modify the relative hierarchical positions of cortical areas. Overall, our model suggests that the pulvinar provides crucial contextual modulation to cortical computations associated with cognition.


SLEEP ◽  
2022 ◽  
Author(s):  
Dimitrios Mylonas ◽  
Sasha Machado ◽  
Olivia Larson ◽  
Rudra Patel ◽  
Roy Cox ◽  
...  

Abstract Study Objectives Converging evidence from neuroimaging, sleep, and genetic studies suggests that dysregulation of thalamocortical interactions mediated by the thalamic reticular nucleus (TRN) contribute to autism spectrum disorder (ASD). Sleep spindles assay TRN function, and their coordination with cortical slow oscillations (SOs) indexes thalamocortical communication. These oscillations mediate memory consolidation during sleep. In the present study, we comprehensively characterized spindles and their coordination with SOs in relation to memory and age in children with ASD. Methods Nineteen children and adolescents with ASD, without intellectual disability, and 18 typically developing (TD) peers, aged 9-17, completed a home polysomnography study with testing on a spatial memory task before and after sleep. Spindles, SOs, and their coordination were characterized during stages 2 (N2) and 3 (N3) non-rapid eye movement sleep. Results ASD participants showed disrupted SO-spindle coordination during N2 sleep. Spindles peaked later in SO upstates and their timing was less consistent. They also showed a spindle density (#/min) deficit during N3 sleep. Both groups showed significant sleep-dependent memory consolidation, but its relations with spindle density differed. While TD participants showed the expected positive correlations, ASD participants showed the opposite. Conclusions The disrupted SO-spindle coordination and spindle deficit provide further evidence of abnormal thalamocortical interactions and TRN dysfunction in ASD. The inverse relations of spindle density with memory suggest a different function for spindles in ASD than TD. We propose that abnormal sleep oscillations reflect genetically mediated disruptions of TRN-dependent thalamocortical circuit development that contribute to the manifestations of ASD and are potentially treatable.


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