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Icardi, J.

Publications and source records attributed to Icardi, J..

4 recordsLinked to original sources

Early Increases in Hippocampal Synchrony Predict Chronic Epileptiform Burden in a Temporal Lobe Epilepsy Model

Temporal lobe epilepsy (TLE), the most common focal epilepsy, is often drug-resistant and arises predominantly in the hippocampus. Disease severity is conventionally assessed by seizure frequency and duration, yet epileptiform activity outside discrete seizures may also track disease progression. Whether this activity reflects hippocampal network reorganization as part of epileptogenesis, and whether such reorganization predicts chronic severity, is unknown. Here, we combined longitudinal two-photon calcium imaging of hippocampal CA1 neurons with repeated 24-hour EEG recordings that quantified epileptiform burden in the same pilocarpine treated mice over 16 weeks. CA1 firing and synchrony rose acutely, subsided during a latent period, and increased again chronically, with synchronized firing organized into brief waves that propagated in a consistent direction. Epileptiform burden followed a similar temporal trajectory and increasingly contained electrographic seizures. CA1 synchrony correlated with epileptiform burden and stratified mice into groups with distinct neuronal and electrographic outcomes. CA1 synchrony measured within three weeks of pilocarpine induction predicted chronic epileptiform burden, identifying early hippocampal synchrony as a candidate imaging biomarker and pointing to an early window for intervention in TLE.

neuroscience↗

Neuronal Silencing and Protection in a Mouse Model of Demyelination

Damage to the myelin sheath that protects axons in the central nervous system is a hallmark pathology of demyelinating diseases like multiple sclerosis. Cuprizone-induced demyelination in mice is a common model for studying demyelination and remyelination. However, the relationship between myelin damage and recovery and neuronal function remains poorly understood. By monitoring hippocampal myelination and neuronal activity in the same mice, we assessed longitudinal changes following cuprizone consumption and remyelination treatment. Upon cuprizone consumption, a rapid decline in neuronal activity preceded slower demyelination. Female mice showed a more intense early decrease in brain activity and a stronger correlation with levels of myelin loss. Remyelination treatment led to increased myelination levels and recovery of neuronal activity compared to vehicle treatment. Changes in single-neuron firing rates during treatment were proportional to the pre-cuprizone firing rate in the same cells, highlighting a potential linkage between the status of myelin recovery and cellular activity.

neuroscience↗

Systemic exposure to COVID-19 virus-like particles modulates firing patterns of cortical neurons in the living mouse brain

Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2) causes a systemic infection that affects the central nervous system. We used virus-like particles (VLPs) to explore how exposure to the SARS-CoV-2 proteins affects brain activity patterns in wild-type (WT) mice and in mice that express the wild-type human tau protein (htau mice). VLP exposure elicited dose-dependent changes in corticosterone and distinct chemokine levels. Longitudinal two-photon microscopy recordings of primary somatosensory and motor cortex neurons that express the jGCaMP7s calcium sensor tracked modifications of neuronal activity patterns following exposure to VLPs. There was a substantial short-term increase in stimulus-evoked activity metrics in both WT and htau VLP-injected mice, while htau mice showed also increased spontaneous activity metrics and increase activity in the vehicle-injected group. Over the following weeks, activity metrics in WT mice subsided, but remained above baseline levels. For htau mice, activity metrics either remain elevated or decreased to lower levels than baseline. Overall, our data suggest that exposure to the SARS-CoV-2 VLPs leads to strong short-term disruption of cortical activity patterns in mice with long-term residual effects. The htau mice, which have a more vulnerable genetic background, exhibited more severe pathobiology that may lead to more adverse outcomes.

neuroscience↗

Recording large-scale, cellular-resolution neuronal activity from freely-moving mice

Current methods for recording large-scale neuronal activity from behaving mice with single-cell resolution require either fixing the mouse head under a microscope or attachment of a recording device to the animals skull. Both of these options significantly affect the animal behavior and hence also the recorded brain activity patterns. Here, we introduce a new method to acquire snapshots of single-cell cortical activity maps from freely-moving mice using a calcium sensor called CaMPARI. CaMPARI has a unique property of irreversibly changing its color from green to red inside active neurons when illuminated with 400nm light. We capitalize on this property to demonstrate cortex-wide activity recording without any head fixation or attachment of a miniaturized device to the mouses head. Multiple cortical regions were recorded while the mouse was performing a battery of behavioral and cognitive tests. We identified task-dependent activity patterns across motor and somatosensory cortices, with significant differences across sub-regions of the motor cortex. This new CaMPARI-based recording method expands the capabilities of recording neuronal activity from freely-moving and behaving mice under minimally-restrictive experimental conditions and provides large-scale volumetric data that are not accessible otherwise.

neuroscience↗