Journal
CEREBRAL CORTEX
Volume 20, Issue 4, Pages 982-996Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/cercor/bhp161
Keywords
glutamate; long-term depression; medial prefrontal cortex; muscarinic acetylcholine receptor; nitric oxide
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Funding
- National Science Council, Taiwan [NSC97-2321-B-006-002-MY2, NSC97-2321-B-006-008]
- National Cheng Kung University [A002, R026]
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Cholinergic neurotransmission in the medial prefrontal cortex (mPFC) is critical for normal processing of cue detection and cognitive performance. However, the mechanism by which cholinergic system modifies mPFC synaptic function remains unclear. Here we show that activation of muscarinic acetylcholine receptors (mAChRs) by carbamoylcholine (CCh) induces long-term depression (CCh-LTD) of excitatory synaptic transmission on mPFC layer V pyramidal neurons. The induction of CCh-LTD is dependent on M-1 mAChR activation but does not require N-methyl-D-aspartate receptor activation or coincident synaptic stimulation. Activation of phospholipase C (PLC), protein kinase C (PKC), and postsynaptic Ca2+ release from inositol 1,4,5-triphosphate (IP3) receptor-sensitive internal stores are required for CCh-LTD induction. The expression of CCh-LTD is likely to be presynaptic because it is accompanied by a decrease in 1/(coefficient of variance)(2) and an increase in synaptic failure and paired-pulse ratio of synaptic responses. CCh-LTD is blocked by nitric oxide (NO) synthase inhibitors, soluble guanylyl cyclase (sGC) inhibitor, and protein kinase G (PKG) inhibitor. Synaptic stimulation of M-1 mAChRs with prolonged paired-pulse low-frequency stimulation also triggers LTD. These results suggest that activation of M-1 mAChRs can induce LTD on mPFC layer V pyramidal neurons through the activation of postsynaptic PLC/PKC/IP3 receptor- and subsequently presynaptic NO/sGC/PKG-dependent signaling processes.
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