Coactivation of pre- and postsynaptic signaling mechanisms determines cell-specific spike-timing-dependent plasticity.
Synapses may undergo long-term increases or decreases in synaptic strength dependent on critical differences in the timing between pre-and postsynaptic activity. Such spike-timing-dependent plasticity (STDP) follows rules that govern how patterns of neural activity induce changes in synaptic strength. Synaptic plasticity in the dorsal cochlear nucleus (DCN) follows Hebbian and anti-Hebbian patterns in a cell-specific manner. Here we show that these opposing responses to synaptic activity result from differential expression of two signaling pathways. Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling underlies Hebbian postsynaptic LTP in principal cells. By contrast, in interneurons, a temporally precise anti-Hebbian synaptic spike-timing rule results from the combined effects of postsynaptic CaMKII-dependent LTP and endocannabinoid-dependent presynaptic LTD. Cell specificity in the circuit arises from selective targeting of presynaptic CB1 receptors in different axonal terminals. Hence, pre- and postsynaptic sites of expression determine both the sign and timing requirements of long-term plasticity in interneurons.
Tzounopoulos
Thanos
T
Department of Cell Biology and Anatomy, Rosalind Franklin University, Chicago Medical School, North Chicago, IL 60064, USA. athanasios.tzounopoulos@rosalindfranklin.edu
Rubio
Maria E
ME
Keen
John E
JE
Trussell
Laurence O
LO
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D063385:Cannabinoid Receptor Modulators / Q000502:physiology; D017626:Cochlear Nucleus / Q000166:cytology / Q000502:physiology / Q000648:ultrastructure; D004594:Electrophysiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D017110:Freeze Substitution; D066298:In Vitro Techniques; D007858:Learning / Q000502:physiology; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D008813:Mice, Inbred ICR; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology; D017661:Receptors, Presynaptic / Q000502:physiology* / Q000648:ultrastructure; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D043884:Receptor, Cannabinoid, CB1; D017661:Receptors, Presynaptic; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases