title: Cholinergic induction of input-specific late-phase LTP via localized Ca2+ release in the visual cortex.
abstract: Acetylcholine facilitates long-term potentiation (LTP) and long-term depression (LTD), substrates of learning, memory, and sensory processing, in which acetylcholine also plays a crucial role. Ca(2+) ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca(2+) dynamics. Here, we investigated dendritic Ca(2+) dynamics evoked by synaptic stimulation and the resulting LTP/LTD in layer 2/3 pyramidal neurons of the rat visual cortex. Under muscarinic stimulation, single-shock electrical stimulation (SES) inducing ∼20 mV EPSP, applied via a glass electrode located ∼10 μm from the basal dendrite, evoked NMDA receptor-dependent fast Ca(2+) transients and the subsequent Ca(2+) release from the inositol 1,4,5-trisphosphate (IP(3))-sensitive stores. These secondary dendritic Ca(2+) transients were highly localized within 10 μm from the center (SD = 5.0 μm). The dendritic release of Ca(2+) was a prerequisite for input-specific muscarinic LTP (LTPm). Without the secondary Ca(2+) release, only muscarinic LTD (LTDm) was induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked LTPm as well as dendritic Ca(2+) release. A single burst consisting of 3 EPSPs with weak stimulus intensities instead of the SES also induced secondary Ca(2+) release and LTPm. LTPm and LTDm were protein synthesis-dependent. Furthermore, LTPm was confined to specific dendritic compartments and not inducible in distal apical dendrites. Thus, cholinergic activation facilitated selectively compartment-specific induction of late-phase LTP through IP(3)-dependent Ca(2+) release.
authors.affiliation: Department of Physiology, College of Medicine, The Catholic University of Korea, Seoul 137-701, South Korea.
authors.forename: Kwang-Hyun
authors.initials: KH
authors.lastname: Cho
authors.forename: Hyun-Jong
authors.initials: HJ
authors.lastname: Jang
authors.forename: Yang-Hyeok
authors.initials: YH
authors.lastname: Jo
authors.forename: Wolf
authors.initials: W
authors.lastname: Singer
authors.forename: Duck-Joo
authors.initials: DJ
authors.lastname: Rhie
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D059329:Cholinergic Neurons / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000502:physiology; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology; D008297:Male; D008845:Microinjections; D018721:Muscarinic Agonists / Q000494:pharmacology*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D051381:Rats; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D018727:Muscarinic Antagonists; D011500:Protein Synthesis Inhibitors; C056639:2-amino-5-phosphopentanoic acid; D002217:Carbachol; D006493:Heparin; D014633:Valine; D002118:Calcium