Microplastics are pervasive environmental contaminants found across diverse ecosystems, inducing toxic effects in a wide range of organisms. However, the neurotoxic effects of thermally degraded polystyrene (T-PS) and its underlying mechanisms remain poorly unexplored. In this study, Caenorhabditis elegans was exposed to environmentally relevant concentrations of T-PS (0.1-100&#
x202f;&#
x3bc;g/L), and endpoints including locomotion behaviors, neuronal development, neurotransmitter levels, and gene expression were assessed. Significant alterations in morphology, crystallinity, elemental composition, and functional groups were observed in T-PS compared to virgin polystyrene (V-PS), indicating that thermal degradation modifies the physicochemical properties of V-PS. Exposure to 10-100&#
x202f;&#
x3bc;g/L T-PS resulted in a more pronounced decrease in head thrashes, body bends, forward turns, and backward turns compared to V-PS. In transgenic nematodes, T-PS exposure significantly impacted fluorescence intensity and the percentage of worms exhibiting neurodegeneration in serotonergic, cholinergic, dopaminergic, and &#
x3b3;-aminobutyric acid (GABA) neurons. Correspondingly, marked reductions were observed in the levels of dopamine, serotonin, GABA, and choline neurotransmitters, alongside significant declines in neurotransmitter-related gene expression (e.g.,
dat-1,
tph-1,
unc-30, and
cha-1). Pearson's correlation analysis revealed a significant positive association between these genes and locomotion behaviors. Furthermore, the absence of locomotion behavior impairment in
dat-1 (
ok157),
tph-1 (
mg280),
unc-30 (
e191), and
cha-1 (
e1152) mutants highlights the pivotal roles of these genes in mediating T-PS-induced neurotoxicity in C. elegans. This study enhances our understanding of the neurotoxic mechanisms of T-PS at environmental concentrations, providing valuable insights into its potential environmental health risks.