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Like 70% of human mutation carriers, rodent models with \u0394GAG mutation such as DYT1 knock\u2010in (KI) mice do not show overt dystonia but have subtle sensorimotor deficits and pattern of abnormal synaptic plasticity within the striatal microcircuits. There is evidence that dysfunction of striatal parvalbumin\u2010reactive (Parv+) fast\u2010spiking interneurons (FSIs) can be involved in dystonic signs. To elucidate the relevance of these GABAergic interneurons in the pathophysiology of DYT1 dystonia, we used in vivo optogenetics to specifically inhibit Parv+ and to detect changes in motor behavior and neuronal activity. Optogenetic fibers were bilaterally implanted into the dorsal striatum of male DYT1 KI mice and wild\u2010type (WT) littermates expressing halorhodopsin (eNpHR3.0) in Parv+ interneurons. While stimulations with yellow light pulses for up to 60\u2009min at different pulse durations and interval lengths did not induce abnormal movements, such as dystonic signs, immunohistochemical examinations revealed genotype\u2010dependent differences. In contrast to WT mice, stimulated DYT1 KI showed decreased striatal neuronal activity, that is, less c\u2010Fos reactive neurons, and increased activation of cholinergic interneurons after optogenetic inhibition of Parv+ interneurons. These findings suggest an involvement of Parv+ interneurons in an impaired striatal network in DYT1 KI mice, but at least short\u2010term inhibition of these GABAergic interneurons is not sufficient to trigger a dystonic phenotype, similar to previously shown optogenetic activation of cholinergic interneurons.<\/jats:p>","DOI":"10.1002\/jnr.25157","type":"journal-article","created":{"date-parts":[[2022,12,22]],"date-time":"2022-12-22T07:31:13Z","timestamp":1671694273000},"page":"448-463","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["In vivo optogenetic inhibition of striatal parvalbumin\u2010reactive interneurons induced genotype\u2010specific changes in neuronal activity without dystonic signs in male\n                    <scp>DYT1<\/scp>\n                    knock\u2010in 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