ACTIVITY-DEPENDENT CHANGES IN GAD AND PREPROTACHYKININ MESSENGER-RNASIN VISUAL-CORTEX OF ADULT MONKEYS

Tachykinin-immunoreactive neurons are a subgroup of the GABA neuronal population in layer IVC of monkey primary visual cortex. Following bri ef periods of monocular deprivation in adult monkeys, immunoreactivity for both GABA and tachykinins is dramatically reduced in layer IV cel ls that lie within the deprived ocular dominance columns of this corti cal area. The present study shows that these activity-dependent change s are associated with changes in mRNA levels but over different time c ourses. Radioactive antisense riboprobes derived from monkey-specific cDNAs were used to localize glutamic acid decarboxylase (GAD) and beta -preprotachykinin (beta PPT) mRNAs by in situ hybridization histochemi stry. GAD and beta PPT mRNAs decreased in deprived ocular dominance co lumns of adult monkeys when neural activity was abolished in one eye b y intraocular injections of tetrodotoxin (TTX). beta PPT mRNA levels f ell within 5 d of deprivation and thus appeared to parallel the fall i n immunodetectable tachykinin levels. By contrast, reduced GAD mRNA le vels were detectable only after 15 d of deprivation and long after the fall in immunoreactive GAD and GABA levels has maximized. These resul ts suggest that tachykinin gene expression is regulated by transcripti onal mechanisms as part of the first response to reduced neural activi ty whereas the initial downregulation of immunoreactive GAD and GABA d epends on posttranscriptional mechanisms. Following a more prolonged p eriod of deprivation, a secondary mechanism for GAD regulation appears to he engaged at the level of gene transcription or possibly by chang es in mRNA stability.