Coordinated expression of muscarinic receptor messenger RNAs in striatal medium spiny neurons

The postsynaptic effects of acetylcholine in the striatum are largely media ted by muscarinic receptors. Two of the five cloned muscarinic receptors (M 1 and M4) are expressed at high levels by the medium spiny neurons-the prin cipal projection neurons of the striatum. Previous studies have suggested t hat M4 muscarinic receptors are found primarily in medium spiny neurons tha t express substance P and participate in the "direct" striatonigral pathway . This view is difficult to reconcile with electrophysiological studies sug gesting that nearly all medium spiny neurons exhibit responses characterist ic of M4 receptors. To explore this apparent discrepancy, the coordinated e xpression of M1-M5 receptor messenger RNAs in identified medium spiny neuro ns was assayed using single-cell reverse transcription-polymerase chain rea ction techniques. Nearly all medium spiny neurons had detectable levels of M1 receptor messenger RNA. Although M4 receptor messenger RNA was detected more frequently in substance P-expressing neurons (70%), it was readily see n in a substantial population of enkephalin-expressing neurons (50%). To pr ovide a quantitative estimate of transcript abundance, quantitative reverse transcription-polymerase chain reaction experiments were performed. These studies revealed that M4 messenger RNA was expressed by both substance P an d enkephalin neurons, but was roughly five-fold higher in abundance in subs tance P-expressing neurons. This quantitative difference provides a means o f reconciling previous estimates of M4 receptor distribution and function. (C) 2001 Published by Elsevier Science Ltd on behalf of IBRO.