Biology subjects

Rillosi, E.

Publications and source records attributed to Rillosi, E..

3 recordsLinked to original sources

bioRxiv2025

Relative phase of membrane potential theta oscillations between individual hippocampal neurons code space

The timing of spikes dictates a neurons impact on downstream circuits and behavior, and spike timing is determined by the membrane potential (Vm). However, due to technical challenges, it has been impossible to analyze the relative timing of Vm dynamics between neurons during behavior. Using large scale membrane voltage imaging, we simultaneously recorded Vm from many individual hippocampal neurons in animals engaged in a virtual spatial task. We found that relative phase of Vm theta oscillations across neurons exhibit gradual or discrete shifts depending on spatial position. This finding extends beyond previous studies showing Vm dynamics in single neurons or spiking activity in multiple neurons, revealing previously unknown evidence for consistent coding of space by spike-independent relative phase of Vm theta dynamics between neurons.

neuroscience↗

bioRxiv2024

Identifying the Brain Circuits that Regulate Pain-Induced Sleep Disturbances

Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP (parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRP in pain-induced sleep disturbances. Inactivating the PBelCGRP neurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRP terminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics. One sentence summaryParabrachial CGRP neurons regulate awakenings to pain.

neuroscience↗

bioRxiv2024

Photothrombosis induced cortical stroke produces electrographic epileptic biomarkers in mice

ObjectiveInterictal epileptiform spikes, high-frequency ripple oscillations, and their co-occurrence (spike ripples) in human scalp or intracranial voltage recordings are well-established epileptic biomarkers. While clinically significant, the neural mechanisms generating these electrographic biomarkers remain unclear. To reduce this knowledge gap, we introduce a novel photothrombotic stroke model in mice that reproduces focal interictal electrographic biomarkers observed in human epilepsy. MethodsWe induced a stroke in the motor cortex of C57BL/6 mice unilaterally (N=7) using a photothrombotic procedure previously established in rats. We then implanted intracranial electrodes (2 ipsilateral and 2 contralateral) and obtained intermittent local field potential (LFP) recordings over several weeks in awake, behaving mice. We evaluated the LFP for focal slowing and epileptic biomarkers - spikes, ripples, and spike ripples - using both automated and semi-automated procedures. ResultsDelta power (1-4 Hz) was higher in the stroke hemisphere than the non-stroke hemisphere in all mice (p<0.001). Automated detection procedures indicated that compared to the non-stroke hemisphere, the stroke hemisphere had an increased spike ripple (p=0.006) and spike rates (p=0.039), but no change in ripple rate (p=0.98). Expert validation confirmed the observation of elevated spike ripple rates (p=0.008) and a trend of elevated spike rate (p=0.055) in the stroke hemisphere. Interestingly, the validated ripple rate in the stroke hemisphere was higher than the non-stroke hemisphere (p=0.031), highlighting the difficulty of automatically detecting ripples. Finally, using optimal performance thresholds, automatically detected spike ripples classified the stroke hemisphere with the best accuracy (sensitivity 0.94, specificity 0.94). SignificanceCortical photothrombosis-induced stroke in commonly used C57BL/6 mice produces electrographic biomarkers as observed in human epilepsy. This model represents a new translational cortical epilepsy model with a defined irritative zone, which can be broadly applied in transgenic mice for cell type specific analysis of the cellular and circuit mechanisms of pathologic interictal activity. Key PointsO_LICortical photothrombosis in mice produces stroke with characteristic intermittent focal delta slowing. C_LIO_LICortical photothrombosis stroke in mice produces the epileptic biomarkers spikes, ripples, and spike ripples. C_LIO_LIAll biomarkers share morphological features with the corresponding human correlate. C_LIO_LISpike ripples better lateralize to the lesional cortex than spikes or ripples. C_LIO_LIThis cortical model can be applied in transgenic mice for mechanistic studies. C_LI

neuroscience↗