Modified human mesenchymal stromal/stem cells restore cortical excitability after focal ischemic stroke in rats.

Allogeneic modified bone marrow-derived human mesenchymal stromal/stem cells (hMSC-SB623 cells) are in clinical development for the treatment of chronic motor deficits after traumatic brain injury and cerebral ischemic stroke. However, their exact mechanisms of action remain unclear. Here, we investigated the effects of this cell therapy on cortical network excitability, brain tissue, and peripheral blood at a chronic stage after ischemic stroke in a rat model.

Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents.

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury. Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2.

Complement factor C1q mediates sleep spindle loss and epileptic spikes after mild brain injury.

Although traumatic brain injury (TBI) acutely disrupts the cortex, most TBI-related disabilities reflect secondary injuries that accrue over time. The thalamus is a likely site of secondary damage because of its reciprocal connections with the cortex. Using a mouse model of mild TBI (mTBI), we found a chronic increase in C1q expression specifically in the corticothalamic system.

Gamma rhythms and visual information in mouse V1 specifically modulated by somatostatin neurons in reticular thalamus.

Visual perception in natural environments depends on the ability to focus on salient stimuli while ignoring distractions. This kind of selective visual attention is associated with gamma activity in the visual cortex. While the nucleus reticularis thalami (nRT) has been implicated in selective attention, its role in modulating gamma activity in the visual cortex remains unknown.

Augmented Reticular Thalamic Bursting and Seizures in Scn1a-Dravet Syndrome.

Loss of function in the Scn1a gene leads to a severe epileptic encephalopathy called Dravet syndrome (DS). Reduced excitability in cortical inhibitory neurons is thought to be the major cause of DS seizures. Here, in contrast, we show enhanced excitability in thalamic inhibitory neurons that promotes the non-convulsive seizures that are a prominent yet poorly understood feature of DS.

Systematic examination of the impact of depolarization duration on thalamic reticular nucleus firing in vivo.

The thalamic reticular nucleus (TRN) is optimally positioned to regulate information processing and state dynamics in dorsal thalamus. Distinct inputs depolarize TRN on multiple time scales, including thalamocortical afferents, corticothalamic 'feedback', and neuromodulation. Here, we systematically tested the concurrent and after-effects of depolarization duration on TRN firing in vivo using selective optogenetic drive.

Distinct Thalamic Reticular Cell Types Differentially Modulate Normal and Pathological Cortical Rhythms.

Integrative brain functions depend on widely distributed, rhythmically coordinated computations. Through its long-ranging connections with cortex and most senses, the thalamus orchestrates the flow of cognitive and sensory information. Essential in this process, the nucleus reticularis thalami (nRT) gates different information streams through its extensive inhibition onto other thalamic nuclei, however, we lack an understanding of how different inhibitory neuron subpopulations in nRT function as gatekeepers.

Combined Optogenetic and Chemogenetic Control of Neurons.

Optogenetics provides an array of elements for specific biophysical control, while designer chemogenetic receptors provide a minimally invasive method to control circuits in vivo by peripheral injection. We developed a strategy for selective regulation of activity in specific cells that integrates opto- and chemogenetic approaches, and thus allows manipulation of neuronal activity over a range of spatial and temporal scales in the same experimental animal. Light-sensing molecules (opsins) are activated by biologically produced light through luciferases upon peripheral injection of a small molecule substrate.

Pinacidil induces vascular dilation and hyperemia in vivo and does not impact biophysical properties of neurons and astrocytes in vitro.

Vascular and neural systems are highly interdependent, as evidenced by the wealth of intrinsic modulators shared by the two systems. We tested the hypothesis that pinacidil, a selective agonist for the SUR2B receptor found on smooth muscles, could serve as an independent means of inducing vasodilation and increased local blood volume to emulate functional hyperemia. Application of pinacidil induced vasodilation and increased blood volume in the in vivo neocortex in anesthetized rats and awake mice.

A novel p53-inducible apoptogenic gene, PRG3, encodes a homologue of the apoptosis-inducing factor (AIF).

The p53 tumor suppressor protein induces cell cycle arrest or apoptosis in response to cellular stresses. We have identified PRG3 (p53-responsive gene 3), which is induced specifically under p53-dependent apoptotic conditions in human colon cancer cells, and encodes a novel polypeptide of 373 amino acids with a predicted molecular mass of 40.5 kDa.