DEVELOPMENTAL REGULATION OF NICOTINIC ACH RECEPTOR SUBUNIT MESSENGER-RNAS IN THE RAT CENTRAL AND PERIPHERAL NERVOUS SYSTEMS

In the present study we have investigated the anatomical distribution pattern of nAChR alpha 3, alpha 4, beta 2, and beta 4 subunit mRNAs du ring prenatal and perinatal development of the rat CNS and PNS. Three main developmental patterns have been recognized. (1) In the majority of cases studied (caudal brain, spinal cord, dorsal root ganglia, trig eminal and geniculate ganglia) all four subunit mRNAs are initially (E 11-13) detected but, during subsequent prenatal development, the level of some of these subunit mRNAs (alpha 3 and beta 4 in the brain and s pinal cord, alpha 4 and beta 4 in the dorsal root ganglia, alpha 4 in the visceral sensory ganglia, and alpha 3, alpha 4, and beta 4 in the somatic sensory ganglia) become undetectable. (2) In the case of the c erebral cortex a pair of subunit mRNAs (alpha 3-beta 2) is initially ( E12-13) expressed followed by a repression of the alpha 3 subunit (E15 ) and the subsequent (E17-19) induction of the alpha 4 subunit. (3) On ly some subunit mRNAs are initially (E13-15) expressed in the retina ( alpha 3-alpha 4-beta 2-beta 4), parasympathetic or sympathetic motor g anglia (alpha 3-beta 2-beta 4), and vestibulo-cochlear ganglia (alpha 4-beta 2) and their level remains stable throughout prenatal and early postnatal development. Overall, in most central and peripheral struct ures the appearance of nAChR subunit mRNAs is precocious and temporall y related to the timing of neuronal differentiation. In addition, in s everal structures the expression of certain subunits (alpha 3, alpha 4 or beta 4) is transient, although not beta 2. Finally, the comparison of the different regional distribution patterns suggests that a limit ed number of structure-specific receptor isoforms are functional durin g development of CNS and PNS.