Changes in synaptic efficacy underlying learning and memory processes are assumed to be associated with alterations of the protein composition of synapses. Here, we performed a quantitative proteomic screen to monitor changes in the synaptic proteome of four brain areas (auditory cortex, frontal cortex, hippocampus, striatum) during auditory learning. Mice were trained in a shuttle box GO/NO‐GO paradigm to discriminate between rising and falling frequency‐modulated tones to avoid mild electric foot‐shock. Control‐treated mice received corresponding numbers of either the tones or the foot‐shocks. Six hours and 24 h later, the composition of a fraction enriched in synaptic cytomatrix‐associated proteins was compared to that obtained from naïve mice by quantitative mass spectrometry. In the synaptic protein fraction obtained from trained mice, the average percentage (±SEM) of down‐regulated proteins (59.9±0.5%) exceeded that of up‐regulated proteins (23.5±0.8%) in the brain regions studied. This effect was significantly smaller in foot‐shock (42.7±0.6% down, 40.7±1.0% up) and tone controls (43.9±1.0% down, 39.7±0.9% up). These data suggest that learning processes initially induce removal and/or degradation of proteins from presynaptic and postsynaptic cytoskeletal matrices before these structures can acquire a new, post‐learning organization. In silico analysis points to a general role of insulin‐like signalling in this process.
Authors:
Thilo Kähne, Angela Kolodziej, Karl‐Heinz Smalla, Elke Eisenschmidt, Utz‐Uwe Haus, Robert Weismantel, Siegfried Kropf, Wolfram Wetzel, Frank W. Ohl, Wolfgang Tischmeyer, Michael Naumann, Eckart D. Gundelfinger
ABSTRACT
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Scope
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