Synaptic proteome changes in mouse brain regions upon auditory discrimination learning.
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 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.
Institute of Experimental Internal Medicine, Medical School, Otto von Guericke University, Magdeburg, Germany.
Thilo
T
Kähne
Angela
A
Kolodziej
Karl-Heinz
KH
Smalla
Elke
E
Eisenschmidt
Utz-Uwe
UU
Haus
Robert
R
Weismantel
Siegfried
S
Kropf
Wolfram
W
Wetzel
Frank W
FW
Ohl
Wolfgang
W
Tischmeyer
Michael
M
Naumann
Eckart D
ED
Gundelfinger
D000818:Animals; D001307:Auditory Perception / Q000502:physiology*; D001362:Avoidance Learning; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism*; D004193:Discrimination Learning / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020543:Proteome / Q000378:metabolism*; D040901:Proteomics; D013569:Synapses / Q000378:metabolism*
D020543:Proteome