Isabelle Mansuy,
University of Zürich/ETHZ, Switzerland
Learning and memory are dynamic brain functions that are essential for human and animal life. They are remarkable for their extreme complexity, multiple content and intricate mechanisms but also for their fragility, sometimes unreliability, or even their robustness and pathological recurrence in the case of traumatic memory. Their study by experimental psychologists early on, and more recently by neurologists and neurobiologists has delineated several of their important features. A major characteristic of learning and memory is to have distinct temporal phases that may operate successively, simultaneously or separately in different areas of the brain depending on the type of information being processed and its relevance for behavior. These temporal phases comprise the encoding, the consolidation and the storage of information, as well as the retrieval of information upon need and its re-consolidation after use. The quality of each of these phases determines whether the information is properly learned and remembered, or whether it is poorly retained, unsuccessfully retrieved or forgotten.
The cellular and molecular mechanisms operating in nerve cells to sustain these phases are now starting to be understood. These mechanisms engage multiple proteins that function at the surface or inside neuronal cells to trigger a signaling machinery allowing neurons to be active and brain circuits to be plastic. Major intracellular components of this machinery are protein kinases and protein phosphatases. These enzymes function oppositely to control the level of energy and the activity [through the addition or removal of phosphate residues, a process known as phosphorylation or dephosphorylation] of a multitude of cellular constituents such as neurotransmitter receptors, signaling enzymes, transcription and translation factors, etc. Recent studies in which their activity was altered in the mouse brain by modern genetic methods such as transgenesis and gene knockout revealed that protein phosphatases are strong negative regulators of neuronal signaling, and effective molecular constraints on learning and memory. A better understanding of the modes of action of these natural constraints, and of their implication in the development of cognitive disorders should open new perspectives for potential therapeutic approaches to human pathologies affecting learning and memory. |
