Oligodendrocyte progenitor cells (OPCs) receive synaptic input from a diverse range of neurons in the developing and adult brain. Understanding whether the neuronal populations that synapse with OPCs in the healthy brain is altered by demyelination and/or remyelination may support the advancement of neuroprotective or myelin repair strategies being developed for demyelinating diseases such as multiple sclerosis. To explore this possibility, we employed cre-lox transgenic technology to facilitate the infection of OPCs by a modified rabies virus, enabling the retrograde monosynaptic tracing of neuron→OPC connectivity. In the healthy adult mouse, OPCs in the corpus callosum primarily received synaptic input from ipsilateral cortical neurons. Of the cortical neurons, ∼50% were layer V pyramidal cells. Cuprizone demyelination reduced the total number of labeled neurons. However, the frequency/kinetics of mini-excitatory postsynaptic currents recorded from OPCs appeared preserved. Of particular interest, demyeli...

Extracellular recordings in freely moving mice, especially those with movable electrodes (microdrives), are crucial for understanding brain function. However, existing microdrives are often heavy, expensive, fragile, and unsuited for long-term studies with multichannel recordings. The OptoDrive is a new, lightweight (3.2 g), low-cost system for chronic neural recordings and optogenetic manipulation in mice. It features a detachable, 16-channel tungsten-wire electrode assembly with a 3 mm stroke (15 μm step displacement) and an integrated optical fiber. This system enables repeated implantation and explantation without surgery, requiring only gas anesthesia. The OptoDrive has demonstrated stable recordings from the lateral hypothalamus of freely behaving mice for nearly 1 month and successful optogenetic silencing of neuronal activity. In conclusion, OptoDrive offers a cost-effective, compact solution for long-term electrophysiology and optogenetics in freely moving mice.

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...

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...

In frequency tagging, visual stimulation at a frequency (F) of ∼10 Hz has long been known to generate the highest-amplitude response at F in the frequency domain over the human occipital cortex with electroencephalogram and other high temporal-resolution methods. Brain responses are indeed commonly assessed simply at F (i.e., the first harmonic = 1 F ), under the assumption that the response is represented at a single frequency, i.e., “steady-state” or approximately sinusoidal in terms of amplitude over time. This condition is met at stimulus presentation frequencies above ∼4–8 Hz in the visual modality; consequently, frequency tagging has often been limited to F above this “floor.” Here, we support a less-common perspective, that frequency-tagged responses do not need to be steady-state, such that slower F are valid. In this case, it has been shown that is not appropriate to measure nonsinusoidal responses at only F but that nonsinusoidal responses can still be analyzed simply and advantageously in the fr...

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...

Recent research shows that the intention to act on an object alters its neural representation in ways as afforded by underlying sensorimotor processes. For example, the intention to grasp and pick up an object results in representations of the object's weight. But these representations become grasp-specific only immediately before object lift if weight information is relayed through object material. This feature triggers earlier representations regardless of intention probably because material–weight contingencies are overlearned. In contrast, recently learned weight cues should be recalled deliberately during grasp planning resulting in early grasp-specific representations. Here, we examined how action intentions affect the representation of newly acquired color–weight contingencies. We recorded electroencephalography while human participants grasped or reached for objects that varied in shape and density as indicated by their color. Multivariate analyses revealed a grasp-specific reactivation of color du...

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...

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...