plasticity . learning . brain states . neuromodulation . cortical circuits . sensory processing

Neuroplasticity

What mechanisms gate cortical plasticity while maintaining normal brain function?

The main aim of our research is to understand mechanisms that allow cortex to restructure its circuits through experience and learning while maintaining normal brain function. This research explores the restructuring of distinct pathways upon learning and experience, and how global brain-states might contribute to this restructuring. Understanding how cortical circuits are restructured is important for several reasons. First, plasticity of cortical circuits is central to behavior as it allows animals to flexibility to adapt to a dynamic environment. Second, understanding which components of the circuit are plastic will give us insight into how the circuit processes information, i.e. how the system is built. Finally, there is an unmet medical need to promote plasticity in cortical circuits in disease and after injury.

Our laboratory focuses on three main topics, all of which aim to elucidate important overarching questions of how neuronal network plasticity mechanisms link to behavior at different scales:

The first one investigates how the circuits for visual processing are established, either after visual deprivation or during normal development. The second topic investigates how learning restructures cortical circuits and influences visual processing. To this end, we train mice in a virtual reality setting to perform a visual learning task. To assess restructuring and plasticity upon learning, we use combinations of physiological recording methods and optogenetics. Finally, the third topic investigates mechanisms that promote plasticity. Specifically, we are investigating the combinatorial role of different neuromodulators in gating activity and plasticity. We employ optogenetic and pharmacological approaches to manipulate neuromodulatory systems and measure acute and long-term effects on circuits in visual cortex.

Our research is based on the investigation of plasticity mechanisms of neuronal circuits, the development of novel technologies for the chronic manipulation of specific neuronal pathways, and strategies for targeted interventions that enhance cortical plasticity. Thus, our work has important implications not only for the healthy but also for the diseased or impaired nervous system.

After an early developmental phase, the capacity for cortical plasticity is progressively diminished. Consequently, recovery of function after either traumatic injury or stroke is often severely limited. Having the means to selectively augment cortical plasticity in recovery therapy would address a substantial unmet medical need. Importantly, given the large variety of drugs available to modulate the activity of different neuromodulatory systems, understanding the relationship between neuromodulatory activity pattern and increased cortical plasticity has a direct translational potential. For example, it is increasingly likely that in the near future, we will be able to restore sensory function following primary receptor loss. This will come in the form of restoring light sensitivity in a degenerated retina, or by cochlear implants. With any such restoration, cortex will need to adapt and relearn to process sensory input in ways it has not seen previously. Understanding how new information shapes cortical circuits and how cortical plasticity can be enhanced will be a critical component of successful sensory restoration.