Biology subjects

Bedogni, F.

Publications and source records attributed to Bedogni, F..

4 recordsLinked to original sources

bioRxiv2024

Temporal Dynamics of Neocortical Development in Organotypic Mouse Cultures: A Comprehensive Analysis

Murine organotypic brain slice cultures have been widely used in neuroscientific research and are offering the opportunity to study neuronal function under normal and disease conditions. Despite the brought application, the mechanisms governing the maturation of immature cortical circuits in vitro are not well understood. In this study, we present a detailed investigation into the development of the neocortex in vitro. Utilizing a holistic approach, we studied organotypic whole-hemisphere brain slice cultures from postnatal mice and tracked the development of the somatosensory area over a five-week period. Our analysis revealed the maturation of passive and active intrinsic properties of pyramidal cells together with their morphology, closely resembling in vivo development. Detailed Multi-electrode array (MEA) electrophysiological assessments and RNA expression profiling demonstrated stable network properties by two weeks in culture, followed by the transition of spontaneous activity towards more complex patterns including high-frequency oscillations. However, weeks 4 and 5 exhibited increased variability and initial signs of neuronal loss, highlighting the importance of considering developmental stages in experimental design. This comprehensive characterization is vital for understanding the temporal dynamics of the neocortical development in vitro, with implications for neuroscientific research methodologies, particularly in the investigation of diseases such as epilepsy and other neurodevelopmental disorders.

neuroscience↗

bioRxiv2024

Neural precursor cells rescue symptoms of Rett syndrome by activation of the Interferon γ pathway

The beneficial effects of Neural Precursor Cell (NPC) transplantation in several neurological disorders are well established and they are generally mediated by the secretion of immunomodulatory and neurotrophic molecules. We therefore investigated whether Rett syndrome (RTT), that represents the first cause of severe intellectual disability in girls, might benefit from an NPC-based therapy. Using in vitro co-cultures, we demonstrate that, by sensing the pathological context, NPC-secreted factors induce the recovery of morphological and synaptic defects typical of Mecp2 deficient neurons. In vivo, we prove that intracerebral transplantation of NPCs in RTT mice significantly ameliorates neurological functions. To uncover the molecular mechanisms underpinning the mediated benefic effects, we analysed the transcriptional profile of the cerebellum of transplanted animals, disclosing the possible involvement of the Interferon {gamma} (IFN{gamma}) pathway. Accordingly, we report the capacity of IFN{gamma} to rescue synaptic defects, as well as motor and cognitive alterations in Mecp2 deficient models, thereby suggesting this molecular pathway as a potential therapeutic target for RTT.

neuroscience↗

bioRxiv2020

The enhancement of activity rescues the establishment of Mecp2 null neuronal phenotypes

Mecp2 deficiency, the gene responsible for Rett syndrome (RTT), affects brain maturation by impairing neuronal activity, transcription and morphology. These three elements are physiologically linked in a feed-forward cycle where neuronal activity modulates transcription and morphology to further increase network maturity. We hypothesized that the reduced activity displayed by maturing Mecp2 null neurons during development could perturb such cycle, sustaining an improper transcriptional program that, ultimately, impairs neuronal maturation. Accordingly, we show that by enhancing activity within an early time window, Ampakine redirects, in vitro, the development of null neuronal networks towards more physiological routes. Similarly, the administration of the drug to newborn null offspring delays the progression of symptoms, significantly prolonging life span. Our data highlights the role of altered neuronal activity during the establishment of Mecp2 null networks and the importance of such early defects to the typically poor maturity of RTT brain functions in adulthood. We propose the existence of an "early molecular phase" of Rett syndrome, a detailed description of which might disclose relevant targets for new rescue treatments.

neuroscience↗

bioRxiv2019

Somatostatin-Expressing Interneurons Co-Release GABA and Glutamate onto Different Postsynaptic Targets in the Striatum.

The functional contribution of somatostatin-expressing interneurons (SST-INs) to the synaptic organization of the striatum is poorly understood. Using electrophysiological recordings, optogenetic stimulation, and single-cell PCR analysis, we investigated functional patterns of synaptic connectivity in striatal SST-INs expressing channelrhodopsin-2. Photostimulation of these cells induced both glutamatergic excitatory postsynaptic currents (EPSCs) and GABAergic inhibitory postsynaptic currents (IPSCs) in striatal spiny projection neurons (SPNs) and fast-spiking interneurons (FSIs). The two synaptic components showed equally fast onset latencies, suggesting a mechanism of co-transmission. Accordingly, single-cell PCR analysis revealed that individual striatal SST-INs expressed mRNAs for both glutamate and GABA vesicular transporters (VGLUT1 and VGAT, respectively). During relatively prolonged optical stimuli (0.5-1s), IPSC arrays consistently outlasted EPSCs. As a result, photostimulation of SST-INs caused a transient burst of action potentials followed by a prolonged inhibition in postsynaptic cells.\n\nThese data suggest that striatal SST-INs are specialized to locally project synapses exerting a composite excitatory and inhibitory effect through GABA/glutamate co-transmission onto different postsynaptic targets.

neuroscience↗