Several subclasses of striatal interneurons are found in striatum108, with different transcriptional and physiological properties. We separately clustered TH + , CCK + , PTHLH + , and SST+ interneurons in human striatum. The functionality of interneurons in the striatum is diverse, with several subclasses modulating the excitability and inhibition of MSNs in response to various substances, including opioids109. Although we were unable to reference the overall elevation of DNA damage signature to a specific subset of interneurons, our findings suggest striatal interneurons may be particularly vulnerable to a loss of DNA integrity and repair mechanisms in response to changes in neuronal activity by opioids and related perturbations.
