Biology subjects

Modol, L.

Publications and source records attributed to Modol, L..

3 recordsLinked to original sources

bioRxiv2024

A postnatal molecular switch drives the activity-dependent maturation of parvalbumin interneurons

Cortical neurons are specified during embryonic development but often only acquire their mature properties at relatively late stages of postnatal development. This delay in terminal differentiation is particularly prominent for fast-spiking parvalbumin-expressing (PV+) interneurons, which play critical roles in regulating the function of the cerebral cortex. We found that the maturation of PV+ interneurons is triggered by neuronal activity and mediated by the transcriptional cofactor peroxisome proliferator-activated receptor-gamma coactivator 1-alpha (PGC-1). Developmental loss of PGC-1 prevents PV+ interneurons from acquiring unique structural, electrophysiological, synaptic, and metabolic features and disrupts their diversification into distinct subtypes. PGC-1 exerts its function as a master regulator of the differentiation of PV+ interneurons by directly controlling gene expression through a transcriptional complex that includes ERR{gamma} and Mef2c. Our results uncover a molecular switch that translates neural activity into a specific transcriptional program promoting the maturation of PV+ interneurons at the appropriate developmental stage.

neuroscience↗

bioRxiv2023

Somatostatin interneurons control the timing of developmental desynchronization in cortical networks

Synchronous neuronal activity is a hallmark of the early developing brain. In the mouse cerebral cortex, activity decorrelates during the second week of postnatal development, progressively acquiring the characteristic pattern of sparse coding underlying the integration of multidimensional sensory information. The maturation of inhibition seems critical for this process, but the specific types of interneurons involved in this crucial transition of network activity in the developing cortex remain unknown. Using in vivo volumetric and longitudinal two-photon calcium imaging during the period that precedes the change from highly synchronous to decorrelated activity, we identify somatostatin-expressing (SST+) interneurons as critical modulators of this switch. Modulation of the activity of SST+ cells accelerates or delays the decorrelation of cortical network activity, a process that involves regulating the degree of maturation of parvalbumin-expressing (PV+) interneurons. SST+ cells critically link sensory inputs with local circuits controlling the neural dynamics in the developing cortex while modulating the integration of other interneurons into nascent cortical circuits.

neuroscience↗

bioRxiv2018

Modeling driver cells in developing neuronal networks

Spontaneous emergence of synchronized population activity is a characteristic feature of developing brain circuits. Recent experiments in the developing neo-cortex showed the existence of driver cells able to impact the synchronization dynamics when single-handedly stimulated. We have developed a spiking network model capable to reproduce the experimental results, thus identifying two classes of driver cells: functional hubs and low functionally connected (LC) neurons. The functional hubs arranged in a clique orchestrated the synchronization build-up, while the LC drivers were lately or not at all recruited in the synchronization process. Notwithstanding, they were able to alter the network state when stimulated by modifying the temporal activation of the functional clique or even its composition. LC drivers can lead either to higher population synchrony or even to the arrest of population dynamics, upon stimulation. Noticeably, some LC driver can display both effects depending on the received stimulus. We show that in the model the presence of inhibitory neurons together with the assumption that younger cells are more excitable and less connected is crucial for the emergence of LC drivers. These results provide a further understanding of the structural-functional mechanisms underlying synchronized firings in developing circuits possibly related to the coordinated activity of cell assemblies in the adult brain.\n\nAuthor SummaryThere is timely interest on the impact of peculiar neurons (driver cells) and of small neuronal sub-networks (cliques) on operational brain dynamics. We first provide experimental data concerning the effect of stimulated driver cells on the bursting activity observable in the developing entorhinal cortex. Secondly, we develop a network model able to fully reproduce the experimental observations. Analogously to the experiments two types of driver cells can be identified: functional hubs and low functionally connected (LC) drivers. We explain the role of hub neurons, arranged in a clique, for the orchestration of the bursting activity in control conditions. Furthermore, we report a new mechanism, which can explain why and how LC drivers emerge in the structural-functional organization of the enthorinal cortex.

neuroscience↗