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Bovetti, S.

Publications and source records attributed to Bovetti, S..

4 recordsLinked to original sources

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↗

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↗

Extended field-of-view ultrathin microendoscopes for high-resolution two-photon imaging with minimal invasiveness in awake mice

Imaging neuronal activity with high and homogeneous spatial resolution across the field-of-view (FOV) and limited invasiveness in deep brain regions is fundamental for the progress of neuroscience, yet is a major technical challenge. We achieved this goal by correcting optical aberrations in gradient index lens-based ultrathin ([≤] 500 {micro}m) microendoscopes using aspheric microlenses generated through 3D-microprinting. Corrected microendoscopes had extended FOV (eFOV) with homogeneous spatial resolution for two-photon fluorescence imaging and required no modification of the optical set-up. Synthetic calcium imaging data showed that, compared to uncorrected endoscopes, eFOV-microendoscopes led to improved signal-to-noise ratio and more precise evaluation of correlated neuronal activity. We experimentally validated these predictions in awake head-fixed mice. Moreover, using eFOV-microendoscopes we demonstrated cell-specific encoding of behavioral state-dependent information in distributed functional subnetworks in a primary somatosensory thalamic nucleus. eFOV-microendoscopes are, therefore, small-cross-section ready-to-use tools for deep two-photon functional imaging with unprecedentedly high and homogeneous spatial resolution.

neuroscience↗

Extended field-of-view ultrathin microendoscopes with built-in aberration correction for high-resolution imaging with minimal invasiveness

We present a novel approach to correct optical aberrations in ultrathin gradient-index rod lens-based endoscopes using microfabricated aspherical lenses. Corrected microendoscopes have up to 9 folds larger field-of-view compared to uncorrected probes. Using extended field-of-view (eFOV) microendoscopes, we report two-photon imaging of GCaMP6 signals in the mouse hippocampus in vivo with unprecedented combination of high spatiotemporal resolution and minimal invasiveness.

neuroscience↗