Muscarinic cholinergic and glutamatergic reciprocal regulation of expression of hippocampal cholinergic neurostimulating peptide precursor protein gene in rat hippocampus

Hippocampal cholinergic neurostimulating peptide, an undecapeptide original ly isolated from the hippocampus of young rats, enhances acetylcholine synt hesis in rat medial septal nucleus in vitro. Hippocampal cholinergic neuros timulating peptide is derived from the N-terminal region of its 21-kmol.wt precursor protein. The highest expression of the hippocampal cholinergic ne urostimulating peptide precursor protein messenger RNA is in hippocampal py ramidal neurons. In an in vitro rat hippocampal slice, preparation in which electrical stimulation could be delivered to the Schaffer collateral-CA1 p yramidal cell synapse, semi-quantitative non-radioisotopic in situ hybridiz ation, demonstrated that expression of the hippocampal cholinergic neurosti mulating peptide precursor protein messenger RNA is regulated by neuronal a ctivity. Selective inhibition with pharmacological agents revealed that the constitutive hippocampal cholinergic neurostimulating peptide precursor pr otein messenger RNA level can be up-regulated by D-(-)-2-amino-5-phosphono- valeric acid, and that activity-dependent transcription can be inhibited by tetrodotoxin, nifedipine, 6-cyano-7-nitroquinoxaline-2,3-dione, and scopol amine, but not by mecamylamine. These results indicate that septal cholinergic neurons and hippocampal glut amatergic neurons exert a reciprocal influence over the expression of hippo campal cholinergic neurostimulating peptide precursor protein messenger RNA in the hippocampus, and that the activity-dependent and constitutive expre ssions of hippocampal cholinergic neurostimulating peptide precursor protei n messenger RNA may be regulated by different routes, involving calcium inf lux via L-type Ca2+ channels and N-methyl-D-aspartate receptors. (C) 2001 I BRO. Published by Elsevier Science Ltd.