Synaptic proteome changes in mouse brain regions upon auditory discrimination learning |
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Authors: | Kähne Thilo Kolodziej Angela Smalla Karl-Heinz Eisenschmidt Elke Haus Utz-Uwe Weismantel Robert Kropf Siegfried Wetzel Wolfram Ohl Frank W Tischmeyer Wolfgang Naumann Michael Gundelfinger Eckart D |
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Institution: | Institute of Experimental Internal Medicine, Medical School, Otto von Guericke University, Magdeburg, Germany. |
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Abstract: | 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 na?ve mice by quantitative mass spectrometry. In the synaptic protein fraction obtained from trained mice, the average percentage (±SEM) of downregulated proteins (59.9 ± 0.5%) exceeded that of upregulated 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, postlearning organisation. In silico analysis points to a general role of insulin-like signalling in this process. |
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