Homeostatic plasticity stabilizes firing rates of neurons, but the pressure to restore low activity rates can significantly alter synaptic and cellular properties. Most previous studies of homeostatic readjustment to complete activity silencing in rodent forebrain have examined changes after 2 d of deprivation, but it is known that longer periods of deprivation can produce adverse effects. To better understand the mechanisms underlying these effects and to address how presynaptic as well as postsynaptic compartments change during homeostatic plasticity, we subjected mouse cortical slice cultures to a more severe 5 d deprivation paradigm. We developed and validated a computational framework to measure the number and morphology of presynaptic and postsynaptic compartments from super-resolution light microscopy images of dense cortical tissue. Using these tools, combined with electrophysiological miniature excitatory postsynaptic current measurements, and synaptic imaging at the electron microscopy level, we ...

The Cre-lox system is an indispensable tool in neuroscience research for targeting gene deletions to specific cellular populations. Here we assess the utility of several transgenic Cre lines, along with a viral approach, for targeting cerebellar Purkinje cells (PCs) in mice. Using a combination of a fluorescent reporter line ( Ai14 ) to indicate Cre -mediated recombination and a floxed Dystroglycan line ( Dag1flox ), we show that reporter expression does not always align precisely with loss of protein. The commonly used Pcp2Cre line exhibits a gradual mosaic pattern of Cre recombination in PCs from Postnatal Day 7 (P7) to P14, while loss of Dag1 protein is not complete until P30. Ptf1aCre drives recombination in precursor cells that give rise to GABAergic neurons in the embryonic cerebellum, including PCs and molecular layer interneurons. However, due to its transient expression in precursors, Ptf1aCre results in stochastic loss of Dag1 protein in these neurons. NestinCre , which is often described as a “p...

Tic disorders (TD) are characterized by the presence of motor and/or vocal tics. Common neurophysiological frameworks suggest dysregulations of the cortico-striatal-thalamo-cortical (CSTC) brain circuit that controls movement execution. Besides common tics, there are other “non-tic” symptoms that are primarily related to sensory perception, sensorimotor integration, attention, and social cognition. The existence of these symptoms, the sensory tic triggers, and the modifying effect of attention and cognitive control mechanisms on tics may indicate the salience network's (SN) involvement in the neurophysiology of TD. Resting-state functional MRI measurements were performed in 26 participants with TD and 25 healthy controls (HC). The group differences in resting-state functional connectivity patterns were measured based on seed-to-voxel connectivity analyses. Compared to HC, patients with TD exhibited altered connectivity between the core regions of the SN (insula, anterior cingulate cortex, and temporopariet...

Scientific research demands reproducibility and transparency, particularly in data-intensive fields like electrophysiology. Electrophysiology data are typically analyzed using scripts that generate output files, including figures. Handling these results poses several challenges due to the complexity and iterative nature of the analysis process. These stem from the difficulty to discern the analysis steps, parameters, and data flow from the results, making knowledge transfer and findability challenging in collaborative settings. Provenance information tracks data lineage and processes applied to it, and provenance capture during the execution of an analysis script can address those challenges. We present Alpaca (Automated Lightweight Provenance Capture), a tool that captures fine-grained provenance information with minimal user intervention when running data analysis pipelines implemented in Python scripts. Alpaca records inputs, outputs, and function parameters and structures information according to the W...

Following repetitive visual stimulation, post hoc phase analysis finds that visually evoked response magnitudes vary with the cortical alpha oscillation phase that temporally coincides with sensory stimulus. This approach has not successfully revealed an alpha phase dependence for auditory evoked or induced responses. Here, we test the feasibility of tracking alpha with scalp electroencephalogram (EEG) recordings and play sounds phase-locked to individualized alpha phases in real-time using a novel end-point corrected Hilbert transform (ecHT) algorithm implemented on a research device. Based on prior work, we hypothesize that sound-evoked and induced responses vary with the alpha phase at sound onset and the alpha phase that coincides with the early sound-evoked response potential (ERP) measured with EEG. Thus, we use each subject’s individualized alpha frequency (IAF) and individual auditory ERP latency to define target trough and peak alpha phases that allow an early component of the auditory ERP to alig...

Sleep disruption and impaired synaptic processes are common features in neurodegenerative diseases, including Alzheimer's disease (AD). Hyperphosphorylated Tau is known to accumulate at neuronal synapses in AD, contributing to synapse dysfunction. However, it remains unclear how sleep disruption and synapse pathology interact to contribute to cognitive decline. Here, we examined sex-specific onset and consequences of sleep loss in AD/tauopathy model PS19 mice. Using a piezoelectric home-cage monitoring system, we showed PS19 mice exhibited early-onset and progressive hyperarousal, a selective dark-phase sleep disruption, apparent at 3 months in females and 6 months in males. Using the Morris water maze test, we report that chronic sleep disruption (CSD) accelerated the onset of decline of hippocampal spatial memory in PS19 males only. Hyperarousal occurs well in advance of robust forebrain synaptic Tau burden that becomes apparent at 6–9 months. To determine whether a causal link exists between sleep disru...

In measurement, a reference frame is needed to compare the measured object to something already known. This raises the neuroscientific question of which reference frame is used by humans when exploring the environment. Previous studies suggested that, in touch, the body employed as measuring tool also serves as reference frame. Indeed, an artificial modification of the perceived dimensions of the body changes the tactile perception of external object dimensions. However, it is unknown if such a change in tactile perception would occur when the body schema is modified through the illusion of owning a limb altered in size. Therefore, employing a virtual hand illusion paradigm with an elongated forearm of different lengths, we systematically tested the subjective perception of distance between two points [tactile distance perception (TDP) task] on the corresponding real forearm following the illusion. Thus, the TDP task is used as a proxy to gauge changes in the body schema. Embodiment of the virtual arm was ...

Social behavior is important for our well-being, and its dysfunctions impact several pathological conditions. Although the involvement of glutamate is undeniable, the relevance of vesicular glutamate transporter type 3 (VGluT3), a specific vesicular transporter, in the control of social behavior is not sufficiently explored. Since midbrain median raphe region (MRR) is implicated in social behavior and the nucleus contains high amount of VGluT3+ neurons, we compared the behavior of male VGluT3 knock-out (KO) and VGluT3-Cre mice, the latter after chemogenetic MRR-VGluT3 manipulation. Appropriate control groups were included. Behavioral test battery was used for social behavior (sociability, social discrimination, social interaction, resident intruder test) and possible confounding factors (open field, elevated plus maze, Y-maze tests). Neuronal activation was studied by c-Fos immunohistochemistry. Human relevance was confirmed by VGluT3 gene expression in relevant human brainstem areas. VGluT3 KO mice exhibi...

Oligodendrocytes, the myelin-producing glial cells of the central nervous system (CNS), crucially contribute to myelination and circuit function. An increasing amount of evidence suggests that intracellular calcium (Ca2+) dynamics in oligodendrocytes mediates activity-dependent and activity-independent myelination. Unraveling how myelinating oligodendrocytes orchestrate and integrate Ca2+ signals, particularly in relation to axonal firing, is crucial for gaining insights into their role in the CNS development and function, both in health and disease. In this framework, we used the recombinant adeno-associated virus/Olig001 capsid variant to express the genetically encoded Ca2+ indicator jGCaMP8s, under the control of the myelin basic protein promoter. In our study, this tool exhibits excellent tropism and selectivity for myelinating and mature oligodendrocytes, and it allows monitoring Ca2+ activity in myelin-forming cells, both in isolated primary cultures and organotypic spinal cord explants. By live ima...

In the rodent whisker system, active sensing and sensorimotor integration are mediated in part by the dynamic interactions between the motor cortex (M1) and somatosensory cortex (S1). However, understanding these dynamic interactions requires knowledge about the synapses and how specific neurons respond to their input. Here, we combined optogenetics, retrograde labeling, and electrophysiology to characterize the synaptic connections between M1 and layer 5 (L5) intratelencephalic (IT) and pyramidal tract (PT) neurons in S1 of mice (both sexes). We found that M1 synapses onto IT cells displayed modest short-term depression, whereas synapses onto PT neurons showed robust short-term facilitation. Despite M1 inputs to IT cells depressing, their slower kinetics resulted in summation and a response that increased during short trains. In contrast, summation was minimal in PT neurons due to the fast time course of their M1 responses. The functional consequences of this reduced summation, however, were outweighed by...