Lay summary

When an individual undergoes a novel sensory experience the neurons in the brain that handle this information adapt in order to optimize future processing of the same information and to associate it with other inputs. The functional optimization of neuronal processing has previously been measured using electrodes. This has taught us that, after changes in input, the synaptic connections become stronger between some neurons and weaker between others. Another way to express this is 'that some neurons have changed the loudness with which they talk to other neurons'. It was generally believed that the synaptic changes (also called synaptic plasticity) happen in synapses that have long before been established during development of the brain. However, more recently we and others have found that new synapses are continuously formed and lost even in the adult brain, as if neurons are always looking for ways to optimize their connections. The magnitude of these synapse additions and losses is regulated by sensory experience. In the current project we aim to study how sensory input regulates the size and stability of new and old synaptic connections. To do this we use a microscopic technique with which we can peek into the brain of transgenic mice that express a fluorescent marker in particular synapses. This way we can directly monitor the presence and size of synapses. We do this repeatedly over the time course of a month, keeping track of the stable synapses and the ones that appear and disappear. We perform these measurements in a part of the brain that processes information from the whiskers. The sensory input through the whiskers can easily and painlessly be manipulated, so we can compare 'normal' mice with mice that undergo novel sensory experiences or in which we have repeatedly activated neurons. By comparing all these parameters we hope to gain insight in the mechanisms of synaptic plasticity in the intact mouse brain. This is ultimately important for our understanding of learning and memory. New insights from this work will also help to advance the design of new strategies towards memory enhancement and repair in neurological disorders such as Alzheimer's and stroke.