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Papers of the Week

Papers: 21 Oct 2023 - 27 Oct 2023

2023 Oct 25

J Neurophysiol


Increased Astrocytic GLT-1 Expression in Tripartite Synapses is Associated with SCI-Induced Hyperreflexia.


Benson CA, King JF, Kauer SD, Waxman SG, Tan AM


Spasticity is a chronic neurological complication associated with spinal cord injury (SCI), characterized by increased muscle tone and stiffness. A physiological sign of spasticity is hyperreflexia, evident by the loss of evoked rate-dependent depression (RDD) in the monosynaptic spinal circuit, i.e., H-reflex. Although previous work has shown that SCI-induced astrogliosis contributes to hyperexcitability disorders, including neuropathic pain and spasticity, it is unclear how reactive astrocytes can modulate synaptic transmission within the injured spinal cord. To study astrocytes’ role in post-SCI hyperreflexia, we examined GLT-1 and PSD-95 proteins in astrocytes and neurons, respectively, within the ventral horn (lamina IX). The close juxtaposition of GLT-1 and PSD-95 markers is a molecular correlate of tripartite synapses and is thought to be a key element in astrocyte-induced plasticity of neuronal synapses. Our study compared animals with and without SCI-induced hyperreflexia and spasticity, and investigated potential synaptic abnormalities associated with astrocyte involvement. As expected, four weeks after SCI, we observed a loss in evoked H-reflex RDD in hindlimb EMG recordings, i.e., hyperreflexia, in contrast to uninjured Sham. Importantly, our main findings show a significant increase in the presence of GLT-1 – PSD-95 tripartite synapses in the ventral spinal cord motor regions of animals exhibiting SCI-induced hyperreflexia. Taken together, our study provides clear evidence supporting the involvement of astrocyte-neuron synaptic complexes in the in the plasticity-driven progression of chronic spasticity.