Developmental regulation of nicotinic ACh receptor subunit mRNAs in the rat central and peripheral nervous systems

In the present study we have investigated the anatomical distribution pattern of nAChR α3, α4, β2, and β4 subunit mRNAs during 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, trigeminal and geniculate ganglia) all four subunit mRNAs are initially (E11-13) detected but, during subsequent prenatal development, the level of some of these subunit mRNAs (α3 and β4 in the brain and spinal cord, α4 and β4 in the dorsal root ganglia, α4 in the visceral sensory ganglia, and α3, α4, and β4 in the somatic sensory ganglia) become undetectable. (2) In the case of the cerebral cortex a pair of subunit mRNAs (α3-β2) is initially (E12-13) expressed followed by a repression of the α3 subunit (E15) and the subsequent (E17-19) induction of the α4 subunit. (3) Only some subunit mRNAs are initially (E13-15) expressed in the retina (α3-α4-β2-β4), parasympathetic or sympathetic motor ganglia (α3-β2-β4), and vestibulo-cochlear ganglia (α4-β2) and their level remains stable throughout prenatal and early postnatal development. Overall, in most central and peripheral structures the appearance of nAChR subunit mRNAs is precocious and temporally related to the timing of neuronal differentiation. In addition, in several structures the expression of certain subunits (α3, α4 or β4) is transient, although not β2. Finally, the comparison of the different regional distribution patterns suggests that a limited number of structure-specific receptor isoforms are functional during development of CNS and PNS.