Developmental Chlorpyrifos Exposure Disrupts Tectal Circuit Formation and Behavior in Xenopus laevis

Abstract

Developmental exposure to organophosphate pesticides has been associated with adverse neurodevelopmental outcomes, but the circuit-level mechanisms underlying these effects remain poorly understood. Here, we examined how low-level chlorpyrifos (CPF) exposure affects neural circuit maturation and behavior in Xenopus laevis tadpoles. Tadpoles were exposed to 1 {micro}M CPF from developmental stage 42 to stage 49, spanning a critical period of synaptogenesis and circuit refinement. CPF-exposed tadpoles displayed abnormal schooling behavior, characterized primarily by impaired body-axis alignment despite preserved group aggregation, as well as altered spontaneous swimming marked by reduced looping and increased seizure-like activity. Whole-cell recordings from tectal neurons revealed persistent reductions in inhibitory synaptic drive, consistent with altered excitation-inhibition balance. Although acute CPF exposure transiently increased intrinsic excitability of tectal neurons as well as baseline swimming activity, this effect was not maintained after chronic exposure. Morphological analysis of GFP-labeled tectal neurons revealed altered dendritic branching distribution despite no change in total dendritic length or branch number. Together, these findings suggest that developmental CPF exposure disrupts tectal circuit maturation, leading to abnormal neural connectivity and maladaptive behavioral outcomes relevant to neurodevelopmental dysfunction.