Cholinergic Induction of Input-Specific Late-Phase LTP via Localized Ca2+ Release in the Visual Cortex

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. Ca2+ ions serve as a canonical regulator of LTP/LTD but little is known about the effect of acetylcholine on intracellular Ca2+ dynamics. Here, we investigated dendritic Ca2+ 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 similar to 20 m VEPSP, applied via a glass electrode located similar to 10 mu m from the basal dendrite, evoked NMDA receptor-dependent fast Ca2+ transients and the subsequent Ca2+ release from the inositol 1,4,5-trisphosphate (IP3)-sensitive stores. These secondary dendritic Ca2+ transients were highly localized within 10 mu m from the center (SD = 5.0 mu m). The dendritic release of Ca2+ was a prerequisite for input-specific muscarinic LTP (LTPm). Without the secondary Ca2+ release, only muscarinic LTD (LTDm) was induced. D(-)-2-amino-5-phosphopentanoic acid and intracellular heparin blocked LTPm as well as dendritic Ca2+ release. A single burst consisting of 3 EPSPs with weak stimulus intensities instead of the SES also induced secondary Ca2+ 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 IP3-dependent Ca2+ release.