Kole group

General description research

The Kole research group studies the molecular and physiological mechanisms by which neurons and glia interact and mediate neuronal activity patterns. By using advanced electrophysiological and imaging methods, in animals and ex vivo brain preparations, we performed basic characterization studies on myelinated axons to discover novel mechanisms of how electrical impulses are initiated and propagated along the oligodendrocyte and neuronal membranes. Using animal models of demyelination, we found that myelin critically shapes local circuit oscillations via interneuronal inhibition. Recently, we discovered that during demyelinating pathologies, such as multiple sclerosis, the inhibitory circuits are profoundly affected. Altered inhibitory microcircuits explain memory impairments and cognitive dysfunctions in both mice and men. A current research focus is to better understand the molecular mechanisms by which oligodendrocytes and microglia, both implicated in driving cognitive dysfunctions, affect inhibitory circuit functions.

Psychiatric symptoms (or disorders) the group is interested in

We would like to understand how specific glia cells contribute to neuropsychiatric disorders. Using ex vivo organotypic slice preparations from transgenic mice our group can directly study cell-cell physiology and interrogate using viral and genetic tools. These research strategies are currently developed in the context of the iCNS gravitation grant (https://i-cns.nl/). In addition, we are specifically interested in better understand the basis how oligodendrocyte dysfunctions impact circuit activity, or aberrant activity-dependent myelination affects cognition.

Technical approaches

Our group, and in collaboration with the infrastructure offered at the NIN, offers a wide range of tools to study the role of specific proteins on brain microcircuit fucntion. We are in particular interested to study, in collaboration with psychiatry researchers, the molecular basis of neuropsychiatric symptoms. In addition to the current electrophysioligal and optogenetic infrastructure we are establishing long-term imaging approaches to study activity-dependent changes of microglia-synapse or microglia-oligodendrocyte interactions ex vivo, near superresolution (~100 nm) at the timescale of days/weeks. Proteins of interested can as such be visualized with use of transgenice mouse lines and/or human brain tissue.

Keywords: Pyramidal neuron, interneuron, ion channel, axon, synaptic proteins, oligodendrocytes, microglia, myelin, cognitive tests, neocortex.  
 
List of  the matching research domains and/or disorders: Cognitive systems, Arousal and regulatory systems, sensorimotor systems