Haploinsufficiency of Shank3 increases the orientation selectivity of V1 neurons.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder whose hallmarks are social deficits, language impairment, repetitive behaviors, and sensory alterations. It has been reported that patients with ASD show differential activity in cortical regions, for instance, increased neuronal activity in visual processing brain areas and atypical visual perception compared with healthy subjects. The causes of these alterations remain unclear, although many studies demonstrate that ASD has a strong genetic correlation. An example is Phelan-McDermid syndrome, caused by a deletion of the Shank3 gene in one allele of chromosome 22. However, the neuronal consequences relating to the haploinsufficiency of Shank3 in the brain remain unknown. Given that sensory abnormalities are often present along with the core symptoms of ASD, our goal was to study the tuning properties of the primary visual cortex to orientation and direction in awake, head-fixed Shank3+/- mice. We recorded neural activity in vivo in response to visual gratings in the primary visual cortex from a mouse model of ASD (Shank3+/- mice) using the genetically encoded calcium indicator GCaMP6f, imaged with a two-photon microscope through a cranial window. We found that Shank3+/- mice showed a higher proportion of neurons responsive to drifting gratings stimuli than wild-type mice. Shank3+/- mice also show increased responses to some specific stimuli. Furthermore, analyzing the distributions of neurons for the tuning width, we found that Shank3+/- mice have narrower tuning widths, which was corroborated by analyzing the orientation selectivity. Regarding this, Shank3+/- mice have a higher proportion of selective neurons, specifically neurons showing increased selectivity to orientation but not direction. Thus, the haploinsufficiency of Shank3 modified the neuronal response of the primary visual cortex.

jYCaMP: an optimized calcium indicator for two-photon imaging at fiber laser wavelengths.

Femtosecond lasers at fixed wavelengths above 1,000 nm are powerful, stable and inexpensive, making them promising sources for two-photon microscopy. Biosensors optimized for these wavelengths are needed for both next-generation microscopes and affordable turn-key systems. Here we report jYCaMP1, a yellow variant of the calcium indicator jGCaMP7 that outperforms its parent in mice and flies at excitation wavelengths above 1,000 nm and enables improved two-color calcium imaging with red fluorescent protein-based indicators.