POSTNATAL-DEVELOPMENT OF MUSCARINIC AUTORECEPTORS MODULATING ACETYLCHOLINE-RELEASE IN THE SEPTOHIPPOCAMPAL CHOLINERGIC SYSTEM - II - CELL BODY REGION - SEPTUM

We studied the postnatal development of the release of acetylcholine ( ACh) and of presynaptic, release-inhibiting muscarinic autoreceptors i n the cell body region of the septohippocampal cholinergic pathway. To this end, septal slices (350 mu m thick) from rats of various postnat al ages (postnatal day 3 [P3] to P16) were preincubated with [H-3]chol ine and stimulated twice (S-1, S-2: 360 pulses, 2 ms, 3 Hz, 60 mA) dur ing superfusion with physiological buffer containing hemicholinium-3 ( 10 mu M). In parallel, the activities of hemicholinium-sensitive high- affinity choline uptake (HACU, in synaptosomes) and of choline acetylt ransferase (ChAT, in crude homogenates) were determined as markers for the development of cholinergic functions. In septal slices preincubat ed with [H-3]choline, the electrically evoked overflow of H-3 at S-1 i ncreased from 0.31% (P3) to 2.10% of tissue H-3 (P16), the latter valu e being still lower than that of septal slices from adult rats (3.46% of tissue H-3). Already at P3, the evoked overflow of H-3 was Ca2+-dep endent and sensitive to tetrodotoxin, indicating an action potential-e voked exocytotic mechanism of ACh release early after birth. Presence of the muscarinic agonist oxotremorine(l mu M) significantly inhibited the evoked ACh release in septal slices beginning from P5: no signifi cant effect was detectable at P3. The ACh esterase inhibitor physostig mine (1 mu M) exhibited significant inhibitory effects from P13 onward s. The muscarinic antagonist atropine (1 mu M) enhanced the evoked ACh release only in septal tissue from adult rats. The specific activitie s of HACU, or ChAT showed a 2- or 8-fold increase, respectively, from P3 to P16. In conclusion, presynaptic cholinergic functions seem to de velop almost in parallel both in the cell body and the target area of the septohippocampal projection: also in the septal region nerve termi nals on axon collaterals are endowed very early (at least at P3) with the apparatus for action potential-induced, exocytotic release of ACh. In contrast, the appearance of feedback inhibition via presynaptic mu scarinic autoreceptors is delayed. Autoinhibition due to endogenously released ACh can be detected only later, most probably when endogenous ACh concentrations in the septal nuclei have reached a threshold valu e. (C) 1998 Elsevier Science B.V. All rights reserved.