Transcriptomic encoding of sensorimotor transformation in the midbrain

Abstract

Sensorimotor transformation, a process that converts sensory stimuli into motor actions, is critical for the brain to initiate behaviors. Although the circuitry involved in sensorimotor transformation has been well delineated, the molecular logic behind this process remains poorly understood. Here, we performed high-throughput and circuit-specific single-cell transcriptomic analyses of neurons in the superior colliculus (SC), a midbrain structure implicated in early sensorimotor transformation. We found that SC neurons in distinct laminae express discrete marker genes. Of particular interest, Cbln2 and Pitx2 are key markers that define glutamatergic projection neurons in the optic nerve (Op) and intermediate gray (InG) layers, respectively. The Cbln2+ neurons responded to visual stimuli mimicking cruising predators, while the Pitx2+ neurons encoded prey-derived vibrissal tactile cues. By forming distinct input and output connections with other brain areas, these neuronal subtypes independently mediate behaviors of predator avoidance and prey capture. Our results reveal that, in the midbrain, sensorimotor transformation for different behaviors may be performed by separate circuit modules that are molecularly defined by distinct transcriptomic codes.

Functional Organisation of the Mouse Superior Colliculus

“…Note that PITX2+ SC neurons are involved in turning and while they are concentrated in lateral SC are also present in medial SC. The connection pattern of PITX2+ neurons is similar to that found for non-specific tracing from lateral SC (Masullo et al, 2019;Xie et al, 2021). This suggests that while areas involved in turning have stronger connections with lateral SC, they are also connected to medial SC.…”

“…Another population of sensory-related neurons is labelled by GRP (Gale and Murphy, 2014). In the lower superficial gray and optic layer, neurons can be targeted using expression of PV (Shang et al, 2015), NSTR1 (Gale and Murphy, 2014), CAMK2 (Wei et al, 2015), CBLN2 (Xie et al, 2021), SP (ZHOU et al, 2017) and DRD2 (Montardy et al, 2021). The intermediate layers can be targeted with PITX2 (Masullo et al, 2019;Xie et al, 2021) and DRD2 (Montardy et al, 2021) expression.…”

“…In the lower superficial gray and optic layer, neurons can be targeted using expression of PV (Shang et al, 2015), NSTR1 (Gale and Murphy, 2014), CAMK2 (Wei et al, 2015), CBLN2 (Xie et al, 2021), SP (ZHOU et al, 2017) and DRD2 (Montardy et al, 2021). The intermediate layers can be targeted with PITX2 (Masullo et al, 2019;Xie et al, 2021) and DRD2 (Montardy et al, 2021) expression. Cell types in the deep layers of SC, which have been defined on the basis of morphological and intrinsic electrophysiological properties, currently lack equivalent genetic markers (Bednárová, Grothe and Myoga, 2018).…”

“…Circuits in lateral motor-related SC appear more important in triggering pursuit behaviours. Inhibition of lateral motor-related SC neurons (subthalamus or SNc-projecting) (Shang et al, 2019;Huang et al, 2021), or neurons concentrated in lateral motor-related SC (PITX2+) (Masullo et al, 2019) impairs pursuit, that is movements towards prey (Shang et al, 2019;Huang et al, 2021;Xie et al, 2021), food or conspecifics (Huang et al, 2021). Inhibition of lateral SC also affects the direction (Vale, 2020) but not the speed of escape behaviour (Vale, 2020) (Shang et al, 2019;Huang et al, 2021).…”

“…Pursuitassociated connections (zona incerta and VMHvl) also contact the intermediate layers. In the case of escape, DRD2+ and PITX2+ neurons both have patchy labelling in the intermediate layer of SC, but have different projections, and activation of the former can trigger escape, suggesting that some intermediate layer neurons are involved in triggering escape (Masullo et al, 2019;Montardy et al, 2021;Xie et al, 2021). However, deep layers of SC alone are innervated by VMHdm/c (Benavidez et al, 2021), and dPAG also gets more input from the deep layers of SC than intermediate layers (Evans et al, 2018).…”