Morgese, F. | bioRxiv Science

bioRxiv2026

A collicular somatostatinergic circuit gates sensory access to action

Animals are exposed to far more sensory information than can be converted into action and must prioritise behaviourally salient events. Although salience is commonly studied as modulation of sensory representations, stimulus prioritisation may also arise at premotor stages, through mechanisms that regulate the readiness of action-generating circuits to be recruited by sensory input. The superior colliculus links visual signals to spatially directed orienting and contains Pitx2-expressing spatial-motor modules that coordinate spatially targeted actions, providing a substrate for premotor regulation of sensory access to action. However, the circuit elements that regulate this access remain unknown. Here we identify an intersectionally targeted population of somatostatin-expressing inhibitory neurons in the mouse superior colliculus that is, at the population level, suppressed during orienting movements and visual stimulation. These neurons provide input to Pitx2-expressing spatial-motor modules, and their optogenetic silencing increased retinally evoked firing in Pitx2 neurons, showing that somatostatinergic inhibition constrains the visual recruitment of collicular motor output. Increasing somatostatinergic tone reduced interception of low- and intermediate-contrast visual targets while sparing responses to high-contrast targets, consistent with graded control of sensory access to action. Cholecystokinin-expressing inhibitory neurons and multiple cortical and subcortical regions provide anatomical input to the somatostatinergic population, identifying candidate routes for local and context-dependent regulation. Together, these findings establish somatostatinergic inhibition as a premotor control point that regulates the readiness of spatial-motor circuits for sensory recruitment and identify a circuit architecture through which the behavioural impact of salient sensory events could be regulated downstream of sensory encoding.

neuroscience↗

bioRxiv2020

Genomic stability of Self-inactivating Rabies

Transsynaptic viral vectors provide means to gain genetic access to neurons based on synaptic connectivity and are essential tools for the dissection of neural circuit function. Among them, the retrograde monosynaptic {Delta}G-Rabies has been widely used in neuroscience research. A recently developed engineered version of the {Delta}G-Rabies, the non-toxic self-inactivating (SiR) virus, represents the first tool for open-ended genetic manipulation of neural circuits. However, the high mutational rate of the rabies virus poses a risk that mutations targeting the key genetic regulatory element in the SiR genome could emerge and revert it to a canonical {Delta}G-Rabies. Such revertant mutations have recently been identified in a SiR batch. To address the origin, incidence and relevance of these mutations, we investigated the genomic stability of SiR in vitro and in vivo. We found that "revertant" mutations are rare and accumulate only when SiR is extensively amplified in vitro, particularly in suboptimal production cell lines that have insufficient levels of TEV protease activity. Moreover, we confirmed that SiR-CRE, unlike canonical {Delta}G-Rab-CRE or revertant-SiR-CRE, is non-toxic and that revertant mutations do not emerge in vivo during long-term experiments. HighlightsO_LIRevertant mutations are rare and do not accumulate when SiR is produced in high-TEVp expressing production cell lines C_LIO_LISiR is non-toxic in vivo C_LIO_LIRevertant SiR mutations do not accumulate during in vivo experiments C_LI

neuroscience↗