Abstract: The 5'-flanking region and core regulatory domains that underlie neuronal specific expression of the human .gamma.-aminobutyric acid type A (GABA.sub.A) receptor .beta.1 subunit gene are identified herein. Sequence analysis, mapping of transcriptional initiation sites, and transfection of reporter gene constructs into primary cultures demonstrate that neuronal and region specific activity resides in a TATA-less minimal promoter of 186 bp, comprising an initiator, the major transcriptional start site, a presumptive TFIID binding site, and an enhancer. Enhancer sequence contained within a 26 bp region at the 5'-end of the minimal promoter is essential for activity but not for tissue specificity. Moreover, .beta.1 promoter activity is subject to autologous inhibition, indicating that GABA-induced receptor mRNA downregulation results from an inhibition of gene transcription.