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Both ASR and PPI depend on noradrenergic transmission, yet the modulatory role of the locus coeruleus (LC) remains controversial. Clonidine (0.05\u2009mg\/kg, i.p.), an alpha2\u2010adrenoreceptor agonist, strongly reduced the ASR amplitude. In contrast, chemogenetic LC inhibition only mildly suppressed the ASR and did affect the PPI in virus\u2010transduced rats. The canine adenovirus type 2 (CAV2)\u2013based vector carrying a gene cassette for the expression of inhibitory receptors (hM4Di) and noradrenergic cell\u2013specific promoter (PRSx8) had high cell\u2010type specificity (94.4\u00a0\u00b1\u00a03.1%) but resulted in heterogeneous virus transduction of DbH\u2010positive LC neurons (range: 9.2\u201394.4%). Clozapine\u2010N\u2010oxide (CNO; 1\u00a0mg\/kg, i.p.), a hM4Di actuator, caused the firing cessation of hM4Di\u2010expressing LC neurons, yet complete inhibition of the entire population of LC neurons was not achieved. Case\u2010based immunohistochemistry revealed that virus injections distal (&gt; 150\u00a0\u03bcm) to the LC core resulted in partial LC transduction, while proximal (&lt; 50\u2009\u03bcm) injections caused neuronal loss due to virus neurotoxicity. Neither the ASR nor PPI differed between the intact and virus\u2010transduced rats. Our results suggest that a residual activity of virus\u2010non\u2010transduced LC neurons might have been sufficient for mediating an unaltered ASR and PPI. Our study highlights the importance of a case\u2010based assessment of the virus efficiency, specificity, and neurotoxicity for targeted cell populations and of considering these factors when interpreting behavioral effects in experiments employing chemogenetic modulation.<\/jats:p>","DOI":"10.1111\/ejn.16550","type":"journal-article","created":{"date-parts":[[2024,9,30]],"date-time":"2024-09-30T22:15:29Z","timestamp":1727734529000},"page":"6237-6253","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Partial chemogenetic inhibition of the locus coeruleus due to heterogeneous transduction of noradrenergic neurons preserved auditory salience processing in wild\u2010type rats"],"prefix":"10.1111","volume":"60","author":[{"given":"Anna","family":"Kabanova","sequence":"first","affiliation":[{"name":"Department of Physiology of Cognitive Processes Max Planck Institute for Biological Cybernetics  T\u00fcbingen 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