Animal studies and human tissue experiments have demonstrated that traumatic brain injury (TBI) causes damage to the extracellular matrix (ECM). To test the hypothesis that TBI causes disruption of sulfated glycosaminoglycan (sGAG) in the ECM, we measured levels of sGAG in the cerebrospinal fluid (CSF), blood, and urine, in patients with severe TBI in the acute postinjury period. Samples of CSF, blood, and urine were obtained within 72 h of injury in patients who received external ventricular drains as part of their treatment of severe TBI. Levels of chondroitin and heparan sGAGs were measured, along with their disaccharide constituents. Demographic information, presence of polytrauma, brain injury load, and distance of radiologically visible parenchymal injury from the ventricle were analyzed for correlation with total subtype sGAG levels. Levels were measured in 14 patients ranging in age from 17 to 90 years. CSF sGAG levels were variable among patients, with higher sGAG levels in plasma compared with CS...

Spinal cord injury (SCI) results in the loss of sensory and motor functions due to the inability of mature central nervous system (CNS) neurons to regenerate. Developing robust neural regrowth strategies will be critical for re-establishing corticospinal motor neuron circuits and restoring control over voluntary movement. However, the complex nature of SCI necessitates a multifaceted approach to address several key barriers to regeneration: enhancing the limited intrinsic growth ability of injured adult neurons, mitigating the growth inhibitory signals of the injured spinal cord, and providing a growth-permissive substrate. The intrinsic capacity for axons to regenerate declines precipitously in early postnatal development. There are numerous changes in transcriptional control, epigenetic regulation, cell signaling, and metabolism with CNS maturation (Zheng and Tuszynski, 2023). One well defined change is a decline in growth-promoting phosphatidylinositol 3-kinase (PI3K) signaling as phosphatase and tensi...

Early life stress (ELS) increases susceptibility to cognitive and socioemotional dysfunction by disrupting the neurobiological systems that regulate these behaviors. Animal models provide a valuable tool for investigating the underlying mechanisms, enabling precise manipulation of stress exposure during development. The limited bedding and nesting (LBN) model, which induces maternal stress by restricting access to bedding and nesting materials in rodents, has been instrumental in advancing our understanding of chronic ELS. While this paradigm has been widely adopted, variations in apparatus designs and subtle differences in methodologies could impact consistency across studies. Here, we provide standardized guidelines for a cost-effective open–source mouse LBN apparatus design, which could further enhance the model's utility while supporting pup survival. We additionally present our findings observed during the duration of the LBN paradigm, which spans from postnatal day (PND) 2 to 10, for both dams and pu...

Neurons in the paraventricular nucleus of the thalamus (PVT) integrate visceral and limbic inputs and project to multiple brain regions to bias behavior toward aversive or defensive states. This study examines MOR signaling in anterior PVT neurons in brain slices from untreated and morphine-treated animals. Imaging in a MOR-Cre reporter rat revealed extensive expression in aPVT cells, and the application of [Met]5− enkephalin (ME) induced outward currents which were abolished by the MOR-selective antagonist CTAP. A saturating concentration of ME resulted in desensitization that was blocked by compound 101, indicating a phosphorylation-dependent process. The opioid sensitivity of amygdala-, nucleus accumbens-, and prefrontal cortex-projecting neurons was then examined. Neurons that projected to the amygdala were more sensitive to ME than cortical- and accumbal-projecting cells. Following chronic treatment, tolerance to morphine was found in neurons projecting to the amygdala and nucleus accumbens with a tre...

Rod and cone photoreceptor cells selectively contact different compartments of axon-bearing retinal horizontal cells in the mammalian retina. Cones synapse exclusively on the soma whereas rods synapse exclusively on a large axon terminal compartment. The possibility that rod signals can travel down the axon from terminal to soma has been proposed as a means of producing spectrally opponent interactions between rods and cones, but there is conflicting data about whether this actually occurs. The spectral overlap between rods and cones in mouse makes it difficult to stimulate rod and cone pigments separately. We therefore used optogenetic techniques to analyze photoreceptor inputs into horizontal somas by selectively expressing channelrhodopsin in rods and/or cones. Optogenetic stimulation of rods and cones both evoked large fast inward currents in horizontal cell somas. Cone-driven responses were abolished by eliminating synaptic release in a cone-specific knock-out of the exocytotic calcium sensor, synapto...

Models of experience-dependent neuroplasticity predict that the acquisition and extensive use of a new skill trigger a nonlinear trajectory of neurostructural modifications, where initial expansion of relevant brain areas subsequently (once the skill is acquired) gives way to volumetric renormalization. Such predictions also apply in the domain of language during learning and/or simultaneous management of two (or more) linguistic systems. In a sample of 69 young adult Russian–English bilinguals, we tested the hypothesis that individual differences in bilingual engagement nonlinearly correlate with normalized volume of the hippocampus—a key learning-related brain region particularly amenable to experience-dependent plasticity. Results revealed an inverted U-shape association between second language engagement and left hippocampal gray matter volume. The present results replicate and expand the findings from aging populations, showing a nonlinear pattern of structural hippocampal plasticity in healthy young ...

Lifelong premature ejaculation (LPE) is associated with abnormal brain function, as evidenced by functional MRI (fMRI) studies. This study investigates the stability of brain network architectures in resting-state conditions following perturbation by erotic tasks in individuals with LPE. We assessed the resting-state fMRI in the task-free and task-modulated dataset in the 28 right-hand LPE and 17 age-matched normal controls (NCs). The dynamic functional connectome based on the phase-locking algorithm and ROI-wise gradient mapping was compared. The stability of dynamic functional gradient mapping was measure by linear mixed effects across the two datasets in the LPE and NCs. In both groups, the brain functional gradient exhibited a clear transition from unimodal to transmodal in the principal gradient. Additionally, there was a segregation of primary networks observed in the secondary gradient, either before or after the task. In LPE patients, we observed increased stability in the bilateral dorsal prefront...

Perceptual localization of brief, high-contrast perisaccadic visual probes is grossly erroneous. While this phenomenon has been extensively studied in humans, more needs to be learned about its underlying neural mechanisms. This ideally requires running similar behavioral paradigms in animals. However, during neurophysiology, neurons encountered in the relevant sensory and sensory–motor brain areas for visual mislocalization can have arbitrary, noncardinal response field locations. This necessitates using mislocalization paradigms that can work with any saccade direction. Here, we first established such a paradigm in three male rhesus macaque monkeys. In every trial, the monkeys generated a saccade toward an eccentric target. Once a saccade onset was detected, we presented a brief flash at one of three possible locations ahead of the saccade target location. After an experimentally imposed delay, we removed the saccade target, and the monkeys were then required to generate a memory-guided saccade toward th...

Paying attention to a target talker in multitalker scenarios is associated with its more accurate neural tracking relative to competing non-target speech. This “neural bias” to target speech has largely been demonstrated in experimental setups where target and non-target speech are acoustically controlled and interchangeable. However, in real-life situations this is rarely the case. For example, listeners often look at the talker they are paying attention to while non-target speech is heard (but not seen) from peripheral locations. To enhance the ecological-relevance of attention research, here we studied whether neural bias toward target speech is observed in a spatially realistic audiovisual context and how this is affected by switching the identity of the target talker. Group-level results show robust neural bias toward target speech, an effect that persisted and generalized after switching the identity of the target talker. In line with previous studies, this supports the utility of the speech-tracking...

Dmrta2 (also designated Dmrt5) is a transcriptional regulator expressed in cortical progenitors in a caudomedialhigh/rostrolaterallow gradient with important roles at different steps of cortical development. Dmrta2 has been suggested to act in cortex development mainly by differential suppression of Pax6 and other homeobox transcription factors such as the ventral telencephalic regulator Gsx2 , which remains to be fully demonstrated. Here we have addressed the epistatic relation between Pax6 and Dmrta2 by comparing phenotypes in mutant embryos or embryos overexpressing both genes in various allelic combinations. We show that Dmrta2 cooperates with Pax6 in the maintenance of cortical identity in dorsal telencephalic progenitors and that it acts as a transcriptional repressor of Pax6 to control cortical patterning. Mechanistically, we show that in P19 cells, Dmrta2 acts as a DNA binding-dependent repressor on the Pax6 E60 enhancer and that a point mutation that affects its DNA binding properties identified i...