PT - JOURNAL ARTICLE AU - Vanessa A. Bender AU - Kevin J. Bender AU - Daniel J. Brasier AU - Daniel E. Feldman TI - Two Coincidence Detectors for Spike Timing-Dependent Plasticity in Somatosensory Cortex AID - 10.1523/JNEUROSCI.0176-06.2006 DP - 2006 Apr 19 TA - The Journal of Neuroscience PG - 4166--4177 VI - 26 IP - 16 4099 - http://www.jneurosci.org/content/26/16/4166.short 4100 - http://www.jneurosci.org/content/26/16/4166.full SO - J. Neurosci.2006 Apr 19; 26 AB - Many cortical synapses exhibit spike timing-dependent plasticity (STDP) in which the precise timing of presynaptic and postsynaptic spikes induces synaptic strengthening [long-term potentiation (LTP)] or weakening [long-term depression (LTD)]. Standard models posit a single, postsynaptic, NMDA receptor-based coincidence detector for LTP and LTD components of STDP. We show instead that STDP at layer 4 to layer 2/3 synapses in somatosensory (S1) cortex involves separate calcium sources and coincidence detection mechanisms for LTP and LTD. LTP showed classical NMDA receptor dependence. LTD was independent of postsynaptic NMDA receptors and instead required group I metabotropic glutamate receptors and calcium from voltage-sensitive channels and IP3 receptor-gated stores. Downstream of postsynaptic calcium, LTD required retrograde endocannabinoid signaling, leading to presynaptic LTD expression, and also required activation of apparently presynaptic NMDA receptors. These LTP and LTD mechanisms detected firing coincidence on ∼25 and ∼125 ms time scales, respectively, and combined to implement the overall STDP rule. These findings indicate that STDP is not a unitary process and suggest that endocannabinoid-dependent LTD may be relevant to cortical map plasticity.