The dopaminergic system in the central nervous system is recognized to play an important role in synaptic plasticity and novelty acquisition and is involved in the pathogenesis of various neurological and psychiatric disorders. Using pharmacological and genetic tools, we reported that D4 dopamine (DA) receptor ligands modulate early LTP (40 min) in the stratum oriens (OR) but not in the stratum radiatum (RAD) of hippocampal area CA1 via NMDARs containing NR2B subunits (Herwerth et al., 2011). Next, we want to find out how much endogeneous DA can be released in area CA1 and whether it is sufficient to modulate NR2B NMDARs and early LTP in OR. To examine the distribution of dopaminergic fibers in OR versus RAD, we inject a virus encoding a fluorescent protein which is part of a FLEXed channelrhodopsin construct into the ventral tegmental area (VTA) and/or substantia nigra (SN) of DA active transporter-Cre mice (courtesy of G. Schütz) and reveal DA projections within the hippocampal subregions by fluorescence and/or staining methods three weeks postinfection in fixed brain sections. Furthermore, we apply fast scan cyclic voltammetry (FSCV) in acute slices in order to detect DA release on a phasic timescale (subseconds to seconds) following photostimulation of the dopaminergic fibers. The combination of optogenetics and electrochemistry enables us to generate various DA release patterns in the hippocampus and to monitor the resulting dopamine concentration changes. With these tools, we want to test the hypothesis that the spatial segregation of dopaminergic input to area CA1 is essential for compartmentalizing the dopaminergic control of information flow in the hippocampus.