Superior Colliculus to VTA pathway controls orienting response and influences social interaction in mice

Abstract

Social behaviours characterize cooperative, mutualistic, aggressive or parental interactions that occur among conspecifics. Although the Ventral Tegmental Area (VTA) has been identified as a key substrate for social behaviours, the input and output pathways dedicated to specific aspects of conspecific interaction remain understudied. Here, in male mice, we investigated the activity and function of two distinct VTA inputs from superior colliculus (SC-VTA) and medial prefrontal cortex (mPFC-VTA). We observed that SC-VTA neurons display social interaction anticipatory calcium activity, which correlates with orienting responses towards an unfamiliar conspecific. In contrast, mPFC-VTA neuron population activity increases after initiation of the social contact. While protracted phasic stimulation of SC-VTA pathway promotes head/body movements and decreases social interaction, inhibition of this pathway increases social interaction. Here, we found that SC afferents mainly target a subpopulation of dorsolateral striatum (DLS)-projecting VTA dopamine (DA) neurons (VTADA-DLS). While, VTADA-DLS pathway stimulation decreases social interaction, VTADA-Nucleus Accumbens stimulation promotes it. Altogether, these data support a model by which at least two largely anatomically distinct VTA sub-circuits oppositely control distinct aspects of social behaviour.

The “Primitive Brain Dysfunction” Theory of Autism: The Superior Colliculus Role

“…Evidence suggests that these loops have not only motor but also purely cognitive, functions which have been linked with ASD and other DD (Sathyanesan et al, 2019 ). Apparently, several SC brainstem, thalamic, and basal ganglia loops modulate emotional, sensory, and motor variables in order to make automatic decisions in saccade production (Caligiore et al, 2013 ; Thurat et al, 2015 ; Solié et al, 2022 ). Evidence indicates that following Bayesian instead of “winner takes all” rules, the motor reaction produced by interacting forces at the SC reflects a saccade choice instead of a simple saccade vector (Basso and May, 2017 ).…”

“…Other molecules linked with specific behavioral innate approach, defensive, or attack responses triggered by the SC and related to ASD pathogenesis are acetylcholine (Tokuoka et al, 2020 ), endogenous opioids (da Silva et al, 2013 ), dopamine (Redgrave, 2010 ; Solié et al, 2022 ), corticotropin-release hormone (Daviu et al, 2020 ), adrenergic SC receptors and norepinephrine (Iigaya et al, 2012 ; Li et al, 2018a ; London, 2018 ), and glutamine (Barbano et al, 2020 ).…”

Valproic Acid Affects Neuronal Specification and Differentiation During Early Optic Tectum Development of Zebrafish

“…Ablation studies have shown that while the cortex allows for discrimination of sensory inputs, the SC is necessary to initiate movements toward these events 13 . Recently, this subcortical area has been implicated in influencing social behaviors and has been purported to lead to neurodevelopmental disorders such as Autism Spectrum Disorder (ASD) [14][15][16][17] . Although many studies have shed light on SC function, its microcircuitry and formation continue to be poorly understood.…”

Fetal imidacloprid causes ASD-like impairment of biological motion perception in neonatal chicks

“…As the avian homolog of the mammalian superior colliculus (SC), the tectum is the major subpallial (subcortical) center of multimodal visuo-auditory integration and motor coordination84–87. Recent studies have shown that SC has orientation columns88 and contributes to social interaction89, thus its signal processing could be almost on par with those in the visual cortices. Even after the correspondence between ASD and the integrative nature of SC was theoretically argued for51,90, the link has not been experimentally addressed.…”