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 in the cell body region of the septohippocampal cholinergic pathway. To this end, septal slices (350 microns thick) from rats of various postnatal ages (postnatal day 3 [P3] to P16) were preincubated with [3H]choline and stimulated twice (S1, S2: 360 pulses, 2 ms, 3 Hz, 60 mA) during superfusion with physiological buffer containing hemicholinium-3 (10 microM). In parallel, the activities of hemicholinium-sensitive high-affinity choline uptake (HACU, in synaptosomes) and of choline acetyltransferase (ChAT, in crude homogenates) were determined as markers for the development of cholinergic functions. In septal slices preincubated with [3H]choline, the electrically evoked overflow of 3H at S1 increased from 0.31% (P3) to 2.10% of tissue 3H (P16), the latter value being still lower than that of septal slices from adult rats (3.46% of tissue 3H). Already at P3, the evoked overflow of 3H was Ca(2+)-dependent and sensitive to tetrodotoxin, indicating an action potential-evoked exocytotic mechanism of ACh release early after birth. Presence of the muscarinic agonist oxotremorine (1 microM) significantly inhibited the evoked ACh release in septal slices beginning from P5: no significant effect was detectable at P3. The ACh esterase inhibitor physostigmine (1 microM) exhibited significant inhibitory effects from P13 onwards. The muscarinic antagonist atropine (1 microM) enhanced the evoked ACh release only in septal tissue from adult rats. The specific activities of HACU, or ChAT showed a 2- or 8-fold increase, respectively, from P3 to P16. In conclusion, presynaptic cholinergic functions seem to develop almost in parallel both in the cell body and the target area of the septohippocampal projection: also in the septal region nerve terminals 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 muscarinic 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 value.
Institut für Pharmakologie und Toxikologie, Neuropharmakologisches Labor, Universität Freiburg, Germany.
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D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D017660:Autoreceptors / Q000032:analysis / Q000502:physiology; D002118:Calcium / Q000494:pharmacology; D002794:Choline / Q000493:pharmacokinetics; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D002799:Cholinergic Fibers / Q000737:chemistry* / Q000201:enzymology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006624:Hippocampus / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D018721:Muscarinic Agonists / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D017729:Presynaptic Terminals / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000032:analysis* / Q000502:physiology; D012686:Septal Nuclei / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium
D017660:Autoreceptors; D002800:Cholinesterase Inhibitors; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011976:Receptors, Muscarinic; D014316:Tritium; D013779:Tetrodotoxin; D010095:Oxotremorine; D001285:Atropine; D010830:Physostigmine; D002795:Choline O-Acetyltransferase; D002794:Choline; D000109:Acetylcholine; D002118:Calcium