title: The NO-cGMP-PKG signaling pathway coordinately regulates ERK and ERK-driven gene expression at pre- and postsynaptic sites following LTP-inducing stimulation of thalamo-amygdala synapses.
abstract: Long-term potentiation (LTP) at thalamic input synapses to the lateral nucleus of the amygdala (LA) has been proposed as a cellular mechanism of the formation of auditory fear memories. We have previously shown that signaling via ERK/MAPK in both the LA and the medial division of the medial geniculate nucleus/posterior intralaminar nucleus (MGm/PIN) is critical for LTP at thalamo-LA synapses. Here, we show that LTP-inducing stimulation of thalamo-LA inputs regulates the activation of ERK and the expression of ERK-driven immediate early genes (IEGs) in both the LA and MGm/PIN. Further, we show that pharmacological blockade of NMDAR-driven synaptic plasticity, NOS activation, or PKG signaling in the LA significantly impairs high-frequency stimulation-(HFS-) induced ERK activation and IEG expression in both regions, while blockade of extracellular NO signaling in the LA impairs HFS-induced ERK activation and IEG expression exclusively in the MGm/PIN. These findings suggest that NMDAR-driven synaptic plasticity and NO-cGMP-PKG signaling within the LA coordinately regulate ERK-driven gene expression in both the LA and the MGm/PIN following LTP induction at thalamo-LA synapses, and that synaptic plasticity in the LA promotes ERK-driven transcription in MGm/PIN neurons via NO-driven "retrograde signaling".
authors: Department of Psychology, Yale University, New Haven, CT 06520, USA.
authors: Junli
authors: J
authors: Ping
authors: Glenn E
authors: GE
authors: Schafe
mesh_terms: D000679:Amygdala / Q000201:enzymology* / Q000502:physiology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology; D017774:Long-Term Potentiation / Q000235:genetics / Q000502:physiology*; D008297:Male; D009434:Neural Pathways / Q000201:enzymology / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics; D013788:Thalamus / Q000201:enzymology* / Q000502:physiology
chemical_list: D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D048049:Extracellular Signal-Regulated MAP Kinases; D006152:Cyclic GMP