title: Hippocampal long-term depression is enhanced, depotentiation is inhibited and long-term potentiation is unaffected by the application of a selective c-Jun N-terminal kinase inhibitor to freely behaving rats.
abstract: Synaptic plasticity is regarded as the major candidate mechanism for synaptic information storage and memory formation in the hippocampus. Mitogen-activated protein kinases have recently emerged as an important regulatory factor in many forms of synaptic plasticity and memory. As one of the subfamilies of mitogen-activated protein kinases, extracellular-regulated kinase is involved in the in vitro induction of long-term potentiation (LTP), whereas p38 mediates metabotropic glutamate receptor-dependent long-term depression (LTD) in vitro. Although c-Jun N-terminal kinase (JNK) has also been implicated in synaptic plasticity, the in vivo relevance of JNK activity to different forms of synaptic plasticity remains to be further explored. We investigated the effect of inhibition of JNK on different forms of synaptic plasticity in the dentate gyrus of freely behaving adult rats. Intracereboventricular application of c-Jun N-terminal protein kinase-inhibiting peptide (D-JNKI) (96 ng), a highly selective JNK inhibitor peptide, did not affect basal synaptic transmission but reduced neuronal excitability with a higher dose (192 ng). Application of D-JNKI, at a concentration that did not affect basal synaptic transmission, resulted in reduced specific phosphorylation of the JNK substrates postsynaptic density 95kD protein (PSD 95) and c-Jun, a significant enhancement of LTD and a facilitation of short-term depression into LTD. Both LTP and short-term potentiation were unaffected. An inhibition of depotentiation (recovery of LTP) occurred. These data suggest that suppression of JNK-dependent signalling may serve to enhance synaptic depression, and indirectly promote LTP through impairment of depotentiation.
authors: Department of Neurophysiology, Medical Faculty, Ruhr University Bochum MA 4/149, Universitaetsstrasse 150, 44780 Bochum, Germany.
authors: Honghong
authors: H
authors: Yang
authors: Michael J
authors: MJ
authors: Courtney
authors: Peter
authors: P
authors: Martinsson
authors: Denise
authors: D
authors: Manahan-Vaughan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004594:Electrophysiology; D006624:Hippocampus / Q000502:physiology*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000187:drug effects / Q000502:physiology*; D008297:Male; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D010455:Peptides; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C478085:D-JNKI-1