Postnatal development of muscarinic autoreceptors in the rat brain: lateral and medial septal nuclei and the diagonal band of Broca

The postnatal development of the release of acetylcholine (ACh) and of pres ynaptic, release-inhibiting muscarinic autoreceptors was studied in the lat eral septum (LS), the medial septum (MS) and the diagonal band of Broca (DB ) of the rat brain. To this end, slices (350 mu m thick) containing these b rain regions from rats of various postnatal ages (postnatal day 3 [P3] to P 16, and adult) were pre-incubated with [H-3]choline and stimulated twice (S -1, S-2: 360 pulses, 3 Hz) during superfusion with physiological buffer con taining hemicholinium-3 (10 mu M) In addition, the activity of choline acet yltransferase (ChAT, in crude homogenates) was determined as a marker for t he development of cholinergic functions. At any postnatal age, the electric ally-evoked overflow of tritium from slices pre-incubated with [H-3]choline was highest in the DB, followed by the MS whereas in slices containing the LS, it was only small. In all septal regions, the evoked [H-3]overflow was Ca2+-dependent and tetrodotoxin-sensitive at P3. It increased with postnat al age and reached about 60% of the corresponding adult levels at P16. Pres ence of the muscarinic agonist oxotremorine (1 mu M) during S-2 significant ly inhibited the evoked overflow of tritium beginning from P5: no significa nt effect was detected at P3. The ACh esterase inhibitor physostigmine (1 m u M) exhibited significant inhibitory effects from P13 onwards, whereas the muscarinic antagonist atropine (1 ELM) did not change the evoked ACh relea se. The activity of ChAT, as measured for these septal regions at various p ostnatal ages, correlated well with the [H-3]overflow induced by electrical stimulation. In conclusion, (1) electrically-evoked release of ACh was mea sured for the first time in three septal subregions; (2) the postnatal deve lopment of the presynaptic cholinergic functions: ChAT activity, ACh releas e and muscarinic autoreceptors occurs almost synchronously in these regions of the septal complex and parallels that in the hippocampal formation; (3) as in the hippocampus, the postnatal development of autoreceptors was dela yed with respect to the exocytotic release of ACh. (C) 1999 Elsevier Scienc e B.V. All rights reserved.