Thalamic state controls timing and synchronization of primary somatosensory cortical representations in the awake mouse

The thalamus controls transmission of sensory signals from periphery to cortex, ultimately shaping perception. Despite this significant role, dynamic thalamic gating and the consequences for downstream cortical sensory representations have not been well studied in the awake brain. We optogenetically modulated the ventro-posterior medial thalamus in the vibrissa pathway of the awake mouse, and measured spiking activity in the thalamus, and at the level of primary somatosensory cortex (S1) using extracellular electrophysiology and genetically encoded voltage imaging. Thalamic hyperpolarization significantly amplified thalamic sensory-evoked spiking through enhanced bursting, yet surprisingly the S1 cortical response was not amplified, but instead timing precision was significantly increased, spatial activation more focused, and there was an increased synchronization of cortical inhibitory neurons. A thalamocortical network model implicates the precise timing of feedforward thalamic spiking, and timing-sensitive engagement of synaptic depression, presenting a highly sensitive, state-dependent timing-based gating of sensory signaling to cortex.

Medial Parabrachial Nucleus Is Essential in Controlling Wakefulness in Rats

Activation of the parabrachial nucleus (PB) in the brainstem induced wakefulness in rats, suggesting which is an important nucleus that controls arousal. However, the sub-regions of PB in regulating sleep-wake cycle is still unclear. Here, we employ chemogenetics and optogenetics strategies and find that activation of the medial part of PB (MPB), but not the lateral part, induces continuous wakefulness for 10 h without sleep rebound in neither sleep amount nor the power spectra. Optogenetic activation of glutamatergic MPB neurons in sleeping rats immediately wake rats mediated by the basal forebrain (BF) and lateral hypothalamus (LH), but not the ventral medial thalamus. Most importantly, chemogenetic inhibition of PB neurons decreases wakefulness for 10 h. Conclusively, these findings indicate that the glutamatergic MPB neurons are essential in controlling wakefulness, and that MPB-BF and MPB-LH pathways are the major neuronal circuits.

The Medial Thalamus Plays an Important Role in the Cognitive and Emotional Modulation of Orofacial Pain: A Functional Magnetic Resonance Imaging-Based Study

The thalamus plays a critical role in the perception of orofacial pain. We investigated the neural mechanisms of orofacial pain by exploring the intrinsic functional alterations of the thalamus and assessing the changes in functional connectivity (FC) between the thalamic subregions with significant functional alterations and other brain regions in orofacial pain using the seed-based FC approach. There were 49 participants in the orofacial pain group and 49 controls. Orofacial pain was caused by orthodontic separators. The resting-state functional magnetic resonance imaging data of the two groups were analyzed to obtain the fractional amplitude of low-frequency fluctuations (fALFF) of the thalamus; the thalamic subregions with significant fALFF abnormalities were used as seeds for FC analysis. Student's t-tests were used for comparisons. Pearson's correlation analysis was performed using SPM software. Forty-four participants with orofacial pain (mean age, 21.0 ± 0.9 years; 24 women) and 49 age- and sex-matched controls (mean age, 21.0 ± 2.6 years; 27 women) were finally included. Compared with the control group, the orofacial pain group demonstrated the following: (1) increased function in the dorsal area of the thalamus and decreased function in the medial thalamus; (2) decreased FC between the medial thalamus and 12 brain regions (p < 0.05, family-wise error corrected, voxel > 100); and (3) potential positive and negative correlations between the medial thalamus-seeded FC and visual analog scale score changes (p < 0.05, AlphaSim corrected). The findings show that the medial and dorsal thalami play important roles in orofacial pain perception, and that the medial thalamus likely plays an important role in the cognitive and emotional modulation of orofacial pain.

The medial thalamus plays an important role in the cognitive and emotional modulation of orofacial pain: a functional magnetic resonance imaging-based study

Background The thalamus plays a critical role in the perception of orofacial pain. We investigated the neural mechanisms of orofacial pain by exploring the intrinsic functional alterations of the thalamus and assessing the changes in functional connectivity (FC) between the thalamic subregions with significant functional alterations and other brain regions in orofacial pain using the seed-based FC approach. Methods The study comprised 49 participants in the orofacial pain group and 49 healthy controls. Orofacial pain was caused by orthodontic separators. The resting-state functional magnetic resonance imaging data of the two groups were analyzed to obtain the fractional amplitude of low-frequency fluctuations (fALFFs) of the thalamus, and the thalamic subregions with significant fALFF abnormalities were used as seeds for FC analysis. Student’s t-tests were used to perform comparisons. Pearson’s correlation analysis was performed using SPM software. Results Forty-four participants with orofacial pain (mean age, 21.0±0.9 years; 24 women) and 49 age- and sex-matched healthy controls (mean age, 21.0±2.6 years; 27 women) were finally included. Compared with the control group, the orofacial pain group demonstrated (1) increased function in the dorsal thalamus and decreased function in the medial thalamus; (2) decreased FC between the medial thalamus and 12 brain regions (p<0.05, family-wise error corrected, voxel>100); and (3) potential positive and negative correlations between the medial thalamus-seeded FC and visual analog scale score changes (p<0.05, AlphaSim corrected). Conclusions The findings show that the medial and dorsal thalamus play important roles in orofacial pain perception and that the medial thalamus likely plays an important role in the cognitive and emotional modulation of orofacial pain.

Electroacupuncture Improves IBS Visceral Hypersensitivity by Inhibiting the Activation of Astrocytes in the Medial Thalamus and Anterior Cingulate Cortex

Objective. To explore whether the effect of electroacupuncture (EA) on visceral hypersensitivity (VH) in rats with irritable bowel syndrome (IBS) is related to the changes of astrocyte activation in the medial thalamus (MT) and anterior cingulate cortex (ACC). Method. Male Sprague-Dawley rats were randomly divided into the normal control (NC) group, model control (MC) group, electroacupuncture (EA) group, and fluorocitrate (FCA) group. A model of visceral hypersensitivity was established by neonatal colorectal irritation. In the EA group, needles were inserted into the skin at the Tianshu (ST25) and Shangjuxu (ST37) acupoints, once a day for 7 days. The FCA group received intrathecal injection of FCA on the 1st, 4th, and 7th days. Visceral hypersensitivity was evaluated by the abdominal withdrawal reflex (AWR), and glial fibrillary acidic protein (GFAP) mRNA and protein levels in the MT and ACC were detected by real-time PCR, immunohistochemistry, and western blots. Results. The AWR score in the MC group was significantly higher than in the NC group, and EA and FCA reduced the AWR score of VH rats. GFAP mRNA and protein levels in the MT and ACC of rats in the MC group were significantly increased compared with the NC group. After either electroacupuncture or fluorocitrate, GFAP mRNA and protein levels in the MT and ACC were both clearly reduced. Conclusion. Electroacupuncture alleviates IBS visceral hypersensitivity by inhibiting the activation of astrocytes in the MT and ACC.

Central-positive complexes in ECT-induced seizures: Evidence for thalamocortical mechanisms

Electroconvulsive therapy (ECT) relies on the electrical induction of generalized seizures to treat major depressive disorder and other psychiatric illnesses. These planned procedures provide a clinically relevant model system for studying neurophysiologic characteristics of generalized seizures. We recently described novel central-positive complexes (CPCs), which were observed during ECT-induced seizures as generalized, high-amplitude waveforms with maximum positive voltage over the vertex. Here, we performed a systematic characterization of 6,928 CPC ictal waveforms recorded in 11 patients undergoing right unilateral (RUL) ECT. Analyses of high-density 65-electrode EEG recordings during these 50 seizures allowed evaluation of these CPCs across temporal, spatial, and spectral domains. Peak-amplitude CPC scalp topology was consistent across seizures, showing maximal positive polarity over the midline fronto-central region and maximal negative polarity over the suborbital regions. Total duration of CPCs positively correlated with the time required for return of responsiveness after ECT treatment (r = 0.39, p = 0.005). The rate of CPCs showed a frequency decline consistent with an exponential decay (median 0.032 (IQR 0.053) complexes/second). Gamma band (30-80 Hz) oscillations correlated with the peak amplitude of CPCs, which was also reproducible across seizures, with band power declining over time (r = −0.32, p < 10−7). The sources of these peak potentials were localized to the bilateral medial thalamus and cingulate cortical regions. Our findings demonstrated CPC characteristics that were invariant to participant, stimulus charge, time, and agent used to induce general anesthesia during the procedure. Consistent with ictal waveforms of other generalized epilepsy syndromes, CPCs showed topographic distribution over the fronto-central regions, predictable intra-seizure frequency decline, and correlation with gamma-range frequencies. Furthermore, source localization to the medial thalamus was consistent with underlying thalamocortical pathophysiology, as established in generalized epilepsy syndromes. The consistency and reproducibility of CPCs offers a new avenue for studying the dynamics of seizure activity and thalamocortical networks.