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Updated: Mar 13, 2026
High Resolution Quantitative Synaptic Proteome Profiling of Mouse Brain Regions After Auditory Discrimination Learning
Published on: December 15, 2016
MS imaging and mass spectrometric synaptosome profiling identify PEP-19/pcp4 as a synaptic molecule involved in
Jeroen Aerts1, Annelies Laeremans1, Laurens Minerva1
1KU Leuven, Department of Biology, Laboratory of Neuroplasticity and Neuroproteomics, Naamsestraat 59, 3000 Leuven, Belgium.
Abstract:
The Morris water maze (MWM) spatial learning task has been demonstrated to involve a cognitive switch of action control to serve the transition from an early towards a late learning phase. However, the molecular mechanisms governing this switch are largely unknown. We employed MALDI MS imaging (MSI) to screen for changes in expression of small proteins in brain structures implicated in the different learning phases. We compared mice trained for 3days and 30days in the MWM, reflecting an early and a late learning phase in relation to the acquisition of a spatial learning task. An ion with m/z of 6724, identified as PEP-19/pcp4 by top-down tandem MS, was detected at higher intensity in the dorsal striatum of the late learning phase group compared with the early learning phase group. In addition, mass spectrometric analysis of synaptosomes confirmed the presence of PEP-19/pcp4 at the synapse. PEP-19/pcp4 has previously been identified as a critical determinant of synaptic plasticity in locomotor learning. Our findings extend PEP-19/pcp4 function to spatial learning in the forebrain and put MSI forward as a valid and unbiased research strategy for the discovery and identification of the molecular machinery involved in learning, memory and synaptic plasticity. This article is part of a Special Issue entitled: MALDI Imaging, edited by Dr. Corinna Henkel and Prof. Peter Hoffmann.
Insights
Researchers identified PEP-19/pcp4 as a key protein in spatial learning. This protein
Area of Science:
- Neuroscience
- Molecular Biology
- Biochemistry
Background:
- The Morris water maze (MWM) task involves a cognitive switch for spatial learning.
- Molecular mechanisms behind this learning phase transition are not well understood.
Purpose of the Study:
- To investigate molecular changes during spatial learning using MALDI MS imaging.
- To identify proteins involved in the transition from early to late learning phases in the MWM.
Main Methods:
- Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) was used to screen for small proteins.
- Mice were trained in the MWM for 3 days (early phase) and 30 days (late phase).
- Top-down tandem mass spectrometry and synaptosome analysis were performed.
Main Results:
- A peptide identified as PEP-19/pcp4 showed higher intensity in the dorsal striatum of late-phase learners.
- PEP-19/pcp4 was confirmed to be present at the synapse via mass spectrometry.
- Previous studies linked PEP-19/pcp4 to locomotor learning and synaptic plasticity.
Conclusions:
- PEP-19/pcp4 plays a role in spatial learning within the forebrain.
- MALDI-MSI is a valuable tool for discovering molecular mechanisms in learning and memory.
- Findings advance understanding of synaptic plasticity in spatial learning.
