HUMANIZATION OF SRGAP2C EXPRESSION IN CORTICAL CIRCUITS IMPROVES LEARNING BY PROMOTING INFORMATION ACCUMULATION

Learning can arise through different behavioral strategies, from conservative trial-and-error to exploratory behaviors that favor information accumulation. We show that the human-specific gene SLIT-ROBO Rho GTPase activating protein 2C (SRGAP2C) modifies the learning strategy in mice performing a sensory detection task. SRGAP2C emerged from the ancestral gene SRGAP2A, encoding a postsynaptic protein regulating synaptic development (Dennis et al. 2012; Charrier et al. 2012). Inducing expression of SRGAP2C in cortical pyramidal neurons (CPNs) enables the emergence of human-like features of synaptic development (Charrier et al. 2012; Fossati et al. 2016), increased cortico-cortical connectivity and improved sensory discrimination performance (Schmidt et al. 2021).To test if SRGAP2C expression specifically in CPNs affects learning, we trained adult wild-type (WT) and SRGAP2C mice to learn a Go-NoGo task that involves learning to associate a whisker stimulus with the presence of a water reward. SRGAP2C mice displayed an enhanced drive to lick, an approach that accelerates the learning of stimulus-reward associations at the cost of more punishment timeouts. We show that SRGAP2C mice gather more task-related information in early sessions and exhibit higher mutual information – the information sensory input provides about behavior – later in training. These results reveal that induction of human-specific SRGAP2C expression in cortical circuits drives a shift in learning strategy, favoring information accumulation over punishment avoidance, leading to an improvement in use of perception to guide action. This suggests that evolutionary changes in cortical connectivity induced by SRGAP2C may have contributed to the evolutionary emergence of distinct features of human learning and decision-making.