title: Learning-facilitated long-term depression requires activation of the immediate early gene, c-fos, and is transcription dependent.
abstract: De novo gene transcription is a prerequisite for long-term information storage in the brain. Learning-facilitated synaptic plasticity describes the ability of hippocampal synapses to respond with long-lasting synaptic plasticity to the coupling of afferent stimulation with a spatial learning experience. Strikingly, long-term depression (LTD) is facilitated by context-dependent spatial learning experiences suggesting it may play a role in information storage to enable spatial memory. Here, we investigated if learning-facilitated LTD requires the transcription factor, c-Fos and is transcription-dependent. Novel spatial learning about object-place configurations coupled with weak low frequency afferent stimulation induced robust LTD in control animals that persisted for >24h and was associated with elevations in hippocampal expression of c-Fos. Intracerebral application of a c-fos antisense oligonucleotide prevented the facilitation of LTD by novel spatial learning, inhibited elevations of c-Fos triggered by LTD and impaired spatial learning. The expression of the transcription factor zif268 was unaffected by the c-fos antisense oligonucleotide. Learning-facilitated LTD was prevented by a transcription inhibitor. These data support that learning-facilitated LTD requires elevations in c-Fos and is transcription dependent. The observation that LTD shares key regulatory mechanisms with learning and memory processes argues strongly for a role for this form of synaptic plasticity in long-term information storage in the hippocampus.
authors: Department of Neurophysiology, Medical Faculty, Ruhr University Bochum, Germany.
authors: Anne
authors: A
authors: Kemp
authors: Wolfgang
authors: W
authors: Tischmeyer
authors: Denise
authors: D
authors: Manahan-Vaughan
mesh_terms: D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000502:physiology*; D007858:Learning / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000235:genetics*; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic
chemical_list: D016760:Proto-Oncogene Proteins c-fos
keywords: Actinomycin-D; Antisense oligonucleotide; Hippocampus; Immediate early gene; LTD; Synaptic plasticity