The molecular circadian clock can be found throughout the body and is essential for the synchronizing cellular physiology with the 24 h day. However, the role of the clock in regulating the regenerative potential of the brain has not been explored. We report here that murine NG2-glia, the largest population of proliferative cells in the mature central nervous system, rhythmically express circadian clock genes in a 24 h period, including the critical clock component Bmal1 RNA and BMAL1 protein. Interestingly, daily NG2-glia proliferation preferentially occurs during the time of day in which Bmal1 expression is high, while conditional knockout of Bmal1 decreases both cortical NG2-glia density and cellular proliferation. Furthermore, in a neurotrauma model, we show that pathology-induced NG2-glia proliferation is also dependent on Bmal1 expression. Because circadian rhythm disturbances are common in neurologic disorders across the life span, including in traumatic brain injury, these findings bear significant...

Goal-tracking (GT) rats are sensitive to Pavlovian outcome devaluation while sign-tracking (ST) rats are devaluation insensitive. During outcome devaluation, GT rats flexibly modify responding to cues based on the current value of the associated outcome. However, ST rats rigidly respond to cues regardless of the current outcome value. Prior work demonstrated disconnection of the basolateral amygdala (BLA) and anterior insular cortex (aIC) decreased both GT and ST behaviors. Given the role of these regions in appetitive motivation and behavioral flexibility, we predicted that disrupting BLA to aIC pathway during outcome devaluation would reduce flexibility in GT rats and reduce rigid appetitive motivation in ST rats. We inhibited the BLA to aIC pathway by infusing inhibitory DREADDs (hM4Di-mcherry) or control (mCherry) virus into the BLA and implanted cannulae into the aIC to inhibit BLA terminals using intracranial injections of clozapine N-oxide (CNO). After training, we used a within - subject satiety-in...

Implantation of guide cannulas is a widely used technique to access specific brain areas. Although commercially available, the need to personalize these implants and the high cost prompted us to design open-source customized devices taking advantage of 3D printing technology. Our cannulas consisted in a 3D-printed head mount designed according to the Paxinos coordinates to reach the CA1 area of the hippocampus. To cut guide cannulas to the proper length, we designed and realized an original 3D-printed linear motion apparatus. Polylactic acid thermoplastic polymer was used as printing material. Homemade or commercial cannulas were implanted in 4- to 6-month-old wild-type mice and intrahippocampal injections of amyloid-β peptide at different concentrations were performed. In vivo behavioral studies of novel object recognition indicated that results obtained with homemade versus commercial devices were comparable. Methylene blue injections and Nissl staining confirmed the correct localization of cannulas in t...

The 1/ f spectral slope of the electroencephalogram (EEG) estimated in the γ frequency range has been proposed as an arousal marker that differentiates wake, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Here, we sought to replicate and extend these findings in a large sample, providing a comprehensive characterization of how slope changes with age, sex, and its test-retest reliability as well as potential confounds that could affect the slope estimation. We used 10,255 whole-night polysomnograms (PSGs) from the National Sleep Research Resource (NSRR). All preprocessing steps were performed using an open-source Luna package and the spectral slope was estimated by fitting log-log linear regression models on the absolute power from 30 to 45 Hz separately for wake, NREM, and REM stages. We confirmed that the mean spectral slope grows steeper going from wake to NREM to REM sleep. We found that the choice of mastoid referencing scheme modulated the extent to which electromyogenic, or e...

What we see is intimately linked to how we actively and systematically explore the world through eye movements. However, it is unknown to what degree visual experience during early development is necessary for such systematic visual exploration to emerge. The present study investigated visual exploration behavior in 10 human participants whose sight had been restored only in childhood or adulthood, after a period of congenital blindness because of dense bilateral congenital cataracts. Participants freely explored real-world images while their eye movements were recorded. Despite severe residual visual impairments and gaze instability (nystagmus), visual exploration patterns were preserved in individuals with reversed congenital cataract. Modeling analyses indicated that, similar to healthy control subjects, visual exploration in individuals with reversed congenital cataract was based on the low-level (luminance contrast) and high-level (object components) visual content of the images. Moreover, participant...

Dopamine (DA) is a critical regulator of striatal network activity and is essential for motor activation and reward-associated behaviors. Previous work has shown that DA is influenced by the reward value of food, as well as by hormonal factors that reguate food intake and energy expenditure. Changes in striatal DA signaling also have been linked to aberrant eating patterns. Here we test the effect of leptin, an adipocyte-derived hormone involved in feeding and energy homeostasis regulation, on striatal DA release and uptake. Immunohistochemical evaluation identified leptin receptor (LepR) expression throughout mouse striatum, including on striatal cholinergic interneurons (ChIs) and their extensive processes. Using fast-scan cyclic voltammetry (FSCV), we found that leptin causes a concentration-dependent increase in evoked extra-cellular DA concentration ([DA]o) in dorsal striatum (dStr) and nucleus accumbens (NAc) core and shell in male mouse striatal slices, and also an increase in the rate of DA uptake....

Central pattern generators produce many rhythms necessary for survival (e.g., chewing, breathing, locomotion), and doing so often requires coordination of neurons through electrical synapses. Because even neurons of the same type within a network are often differentially tuned, uniformly applied neuromodulators or toxins can result in uncoordinated activity. In the crab ( Cancer borealis ) cardiac ganglion, potassium channel blockers and serotonin cause increased depolarization of the five electrically coupled motor neurons as well as loss of the normally completely synchronous activity. Given time, compensation occurs that restores excitability and synchrony. One of the underlying mechanisms of this compensation is an increase in coupling among neurons. However, the salient physiological signal that initiates increased coupling has not been determined. Using male C. borealis , we show that it is the loss of synchronous voltage signals between coupled neurons that is at least partly responsible for plastic...

According to a prominent view in neuroscience, visual stimuli are coded by discrete cortical networks that respond preferentially to specific categories, such as faces or objects. However, it remains unclear how these category-selective networks respond when viewing conditions are cluttered, i.e., when there is more than one stimulus in the visual field. Here, we asked three questions: (1) Does clutter reduce the response and selectivity for faces as a function of retinal location? (2) Is the preferential response to faces uniform across the visual field? And (3) Does the ventral visual pathway encode information about the location of cluttered faces? We used fMRI to measure the response of the face-selective network in awake, fixating macaques (two female, five male). Across a series of four experiments, we manipulated the presence and absence of clutter, as well as the location of the faces relative to the fovea. We found that clutter reduces the response to peripheral faces. When presented in isolation,...

The activation of self-destructive cellular programs helps sculpt the nervous system during development, but the molecular mechanisms used are not fully understood. Prior studies have investigated the role of the APP in the developmental degeneration of sensory neurons with contradictory results. In this work, we sought to elucidate the impact of APP deletion in the development of the sensory nervous system in vivo and in vitro. Our in vivo data show an increase in the number of sciatic nerve axons in adult male and female APP-null mice, consistent with the hypothesis that APP plays a pro-degenerative role in the development of peripheral axons. In vitro , we show that genetic deletion of APP delays axonal degeneration triggered by nerve growth factor deprivation, indicating that APP does play a pro-degenerative role. Interestingly, APP depletion does not affect caspase-3 levels but significantly attenuates the rise of axoplasmic Ca2+ that occurs during degeneration. We examined intracellular Ca2+ mechanis...