Biology subjects

Peretto, P.

Publications and source records attributed to Peretto, P..

3 recordsLinked to original sources

bioRxiv2024

Developmental encoding of ultrasound vocalizations in the mouse auditory cortex

Mice communicate through high-frequency ultrasound vocalizations (USVs), which are crucial for social interactions such as courtship and aggression. Although USV representation has been found in adult brain areas along the auditory pathway, including the auditory cortex (ACx), no evidence is available on the neuronal representation of USVs early in life. Using in vivo two-photon calcium imaging, we analyzed ACx layer 2/3 neuronal responses to USVs, pure tones (4-90 kHz), and high-frequency modulated sweeps from postnatal day 12 (P12) to P21. We found that ACx neurons are tuned to respond to USV syllables as early as P12-P13, with an increasing number of responsive cells as the mouse age. By P14, while pure tone responses showed a frequency preference, no syllable preference was observed. Additionally, at P14, USVs, pure tones, and modulated sweeps activate clusters of largely non-overlapping responsive neurons. Finally, we show that while cell correlation decreases with increasing processing of peripheral auditory stimuli, neurons responding to the same stimulus maintain highly correlated spontaneous activity after circuits have attained mature organization, forming neuronal sub-networks sharing similar functional properties.

neuroscience↗

bioRxiv2024

Dynamic spatiotemporal activation of a pervasive neurogenic competence in striatal astrocytes supports continuous neurogenesis following injury

Adult brain neural stem cells (NSCs) are conventionally regarded as rare cells restricted to two niches: the subventricular zone (SVZ) and the subgranular zone. Parenchymal astrocytes can also contribute to neurogenesis after injury, however the prevalence, distribution, and behaviour of these latent NSCs remained elusive. To tackle these issues, we reconstructed the spatiotemporal pattern of striatal astrocytes neurogenic activation after excitotoxic lesion in mice. Our results indicate that a neurogenic potential is broadly distributed throughout the striatum but is focally activated at the lesion border. In this region, similarly to canonical niches, steady state neurogenesis is ensured by the continuous stochastic activation of local astrocytes. Activated astrocytes quickly return to quiescence, while their progeny locally proliferate for about 10 days following a stochastic behaviour that features an acceleration in differentiation propensity. Notably, striatal astrocytes activation rate matches that of SVZ astrocytes indicating a comparable prevalence of NSC potential.

neuroscience↗

bioRxiv2022

Nr2f1-dependent shaping of mitochondrial architecture in newborn mouse hippocampal neurons unravels novel insights into the neurodevelopmental disorder BBSOAS

The nuclear receptor Nr2f1 plays a key role during cortical development by acting as a strong transcriptional regulator in embryonic and postnatal neural cells. In humans, its mutations cause the Bosch-Boonstra-Schaaf optic atrophy-intellectual syndrome (BBSOAS), a rare neurodevelopmental disorder characterized by multiple clinical features including optic nerve atrophy, intellectual disability, and autistic traits. In this study by genome-wide and in silico analyses we found that key factors for mitochondrial function and dynamics represent potential genomic targets under direct Nr2f1 transcriptional control in neurons. Although mitochondrial dysfunction is increasingly implicated in neurodevelopmental disorders, whether and how Nr2f1 can regulate mitochondria function in neural cells is still completely unknown. To address these questions, we have combined mouse genetics, neuroanatomical and imaging approaches. To genetically manipulate Nr2f1 function in newborn neurons we focused on the adult mouse hippocampal dentate gyrus, a site of persistent neurogenesis where Nr2f1 is highly expressed. We showed that conditional Nr2f1 loss-of-function within the hippocampal neurogenic niche lead to a reduced mitochondrial mass associated to mitochondrial fragmentation in newborn neurons, likely reflecting alteration in mitochondrial dynamics. Accordingly, we showed that the fusion factor Mfn2, which is as a putative Nr2f1 target, is downregulated following both Nr2f1 adult depletion and embryonic haploinsufficiency in mice. Overall, our study provides the first evidence of a crucial role of Nr2f1 in shaping mitochondria in neurons and opens a promising avenue for the identification of new mechanisms implicated in BBSOAS pathogenesis involving mitochondrial dysfunction.

neuroscience↗