Synaptic imbalance and increased inhibition impair motor function in SMA.

ABSTRACT: Movement is executed through balanced excitation-inhibition in spinal motor circuits. Short-term perturbations in one type of neurotransmission are homeostatically counteracted by the opposing type, but prolonged excitation-inhibition imbalance causes dysfunction at both single neuron and circuit levels. However, whether dysfunction in one or both types of neurotransmission leads to pathogenicity in neurodegenerative diseases characterized by select synaptic deficits is not known. Here, we used functional, morphological, and viral-mediated approaches to uncover the pathogenic contribution of unbalanced excitation-inhibition in a mouse model of spinal muscular atrophy (SMA). We show that vulnerable SMA motor circuits fail to respond homeostatically to reduced excitation and instead increase

SUBMITTER: Fletcher EV 

PROVIDER: S-EPMC12412662 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature