Biology subjects

Colombi, I.

Publications and source records attributed to Colombi, I..

4 recordsLinked to original sources

bioRxiv2023

Heterogeneous subpopulations of GABAAR-responding neurons coexist in physiological and pathological mature neuronal networks at increasing scales of complexity

GABA is the main inhibitory neurotransmitter in adults. Depolarizing/excitatory GABA responses have been well characterized at the level of neuronal-population average during typical neurodevelopment and partially in pathology. However, no investigation has specifically assessed whether a mosaicism of cells with either depolarizing/excitatory or hyperpolarizing/inhibitory GABAergic responses exists in adult animals in health/disease. Here, we showed that such mosaicism is present both in adult WT and Down syndrome (DS) mice, as assessed at increasing scales of neuronal-network complexity (cultures, brain- slices, behaving mice). Nevertheless, WT mice presented a lower percentage of cells with depolarizing GABA than DS mice. Restoring the mosaicism of hyperpolarizing and depolarizing GABA-responding neurons to WT levels rescued anxiety behaviour in DS mice. We also found heterogeneous GABAergic responses in mature control and trisomic human iPSC-derived neurons. Thus, a heterogeneous population of GABA-responding cells exists in physiological/pathological conditions in mature mouse and human neurons, possibly contributing to disease-associated behaviours.

neuroscience↗

bioRxiv2020

Real-time detection of bursts in neuronal cultures using a Neuromorphic Auditory Sensor and Spiking Neural Networks

The correct identification of burst events is crucial in many scenarios, ranging from basic neuroscience to biomedical applications. However, none of the burst detection methods that can be found in the literature have been widely adopted for this task. As an alternative to conventional techniques, a novel neuromorphic approach for real-time burst detection is proposed and tested on acquisitions from in vitro cultures. The system consists of a Neuromorphic Auditory Sensor, which converts the input signal obtained from electrophysiological recordings into spikes and decomposes them into different frequency bands. The output of the sensor is sent to a trained spiking neural network implemented on a SpiNNaker board that discerns between bursting and non-bursting activity. This data-driven approach was compared with 8 different conventional spike-based methods, addressing some of their drawbacks, such as being able to detect both high and low frequency events and working in an online manner. Similar results in terms of number of detected events, mean burst duration and correlation as current state-of-the-art approaches were obtained with the proposed system, also benefiting from its lower power consumption and computational latency. Therefore, our neuromorphic-based burst detection paves the road to future implementations for neuroprosthetic applications.

neuroscience↗

bioRxiv2019

The paternally imprinted gene Snord116 regulates cortical neuronal activity

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder that is characterized by rapid eye movement (REM) sleep abnormalities. The disease is caused by genomic imprinting defects that are inherited through the paternal line. Among the genes located in the PWS region on chromosome 15 (15q11-q13), small nucleolar RNA 116 (Snord116) has been previously associated with intrusions of REM sleep into wakefulness in both humans and mice.\n\nHere, we further explore the processes of sleep regulation by studying the PWScrm+/p- mouse line, which carries a paternal deletion of Snord116. We focused on microstructural electrophysiological components of sleep, such as REM sleep features and sleep spindles within NREM sleep. While the former are thought to contribute to neuronal network formation early in brain development, the latter are markers of thalamocortical processes. Both signals are often compromised in neurodevelopmental disorders and influence functional properties of cortical neurons. Thus, we isolated and characterized the intrinsic activity of cortical neurons using in vitro microelectrode array (MEA) studies.\n\nOur results indicate that the Snord116 gene in mice selectively influences REM sleep properties, such as theta rhythms and the organization of REM episodes throughout sleep-wake cycles. Moreover, sleep spindles present specific abnormalities in PWS model systems, indicating that these features of sleep may translate as potential biomarkers in human PWS. We observed abnormalities in the synchronization of cortical neuronal activity that are accounted for by high levels of norepinephrine.\n\nIn conclusion, our results provide support for an important role of Snord116 in regulating brain activity during sleep and, in particular, cortical neuronal properties, thereby opening new avenues for developing interventions in PWS.\n\nSignificance StatementWe found that the Snord116 gene, a major player in Prader-Willi syndrome (PWS), significantly impacts REM sleep and its regulation. Additionally, we found that sleep spindles, a subtle electroencephalography (EEG) marker that occurs during NREM sleep, are dysregulated in PWS mice that carry a paternal deletion of the Snord116 gene. Using a combination of in vivo and in vitro experiments, we identified sleep features at the network and molecular level that suggest that Snord116 is fundamental in the synchronization of neuronal networks. Our study also provides a new pre-clinical tool to investigate the pathophysiology of sleep in PWS.

neuroscience↗

bioRxiv2019

A neuroprosthetic system to restore neuronal communication in modular networks

Recent advances in neurotechnology allow neurological impairments to be treated or reduced by brain machine interfaces and neuroprostheses. To develop energy-efficient and real-time capable devices, neuromorphic computing systems are envisaged as the core of next-generation neurobiohybrid systems for brain repair. We demonstrate here the first exploitation of a neuromorphic prosthesis to restore bidirectional interactions between two neuronal populations, even when one is damaged or completely missing. We used in vitro modular cell cultures to mimic the mutual interaction between neuronal assemblies and created a focal lesion to functionally disconnect the two populations. Then, we employed our neuromorphic prosthesis for two specific applications with future clinical implications: bidirectional bridging to artificially reconnect two disconnected neuronal modules and hybrid bidirectional bridging to replace the activity of one module with a neuromorphic spiking neural network. Our neuroprosthetic system opens up new avenues for the development of novel bioelectrical therapeutics for human applications.

bioengineering↗