Neural networks are able to store information and to learn by adapting the efficacy of synaptic communication between neurons in an activity-dependent way. ‘Synaptic memory’ formation can be bidirectional: synapses can undergo long-term potentiation (LTP) or long-term depression (LTD). These processes participate in behavioral learning in specific ways that depend on the layout of the neuronal circuit that is studied.

In our laboratory, we examine forms of synaptic and non-synaptic plasticity in the cerebellum, a brain area that is involved in fine adaptation of movements, but is involved in cognitive functions as well. In Marr-Albus-Ito models of cerebellar function, LTD at parallel fiber (PF) synapses onto Purkinje cells, which provide the sole output of the cerebellar cortex, is seen as a cellular correlate of motor learning, and forms of associative learning in general. LTD is induced by co-activation of PF synapses with the climbing fiber (CF) input, and is postsynaptically induced and expressed. Next to LTD, we also study a postsynaptic form of LTP at PF synapses that is induced by isolated PF activation and might provide a reversal mechanism for LTD (formally, LTD might also provide a reversal mechanism for LTP). We have recently shown that bidirectional plasticity at PF synapses is governed by induction rules that operate inverse to their counterparts at hippocampal and neocortical synapses: 1) PF-LTD needs larger calcium transients for its induction than LTP, and 2) PF-LTD is kinase-dependent (PKC / aCaMKII), whereas PF-LTP is phosphatase-dependent. Moreover, we have shown that the direction of synaptic gain change (potentiation or depression) depends on whether the CF input was co-activated (LTD) or not (LTP). This control by a qualitatively different heterosynaptic input provides a unique plasticity motif in the brain. In addition to LTD and LTP, we also examine intrinsic plasticity in Purkinje cells. We have shown that the intrinsic excitability of Purkinje cells can be amplified by a downregulation of calcium-dependent SK2-type potassium channels, and that this form of plasticity complements LTD and LTP in information storage.

In the lab, we use patch-clamp recording techniques (incl. patch-clamp recordings from Purkinje cell dendrites), as well as confocal calcium imaging to study the cellular and molecular mechanisms underlying learning and memory. These studies are complemented by the use of additional techniques such as immunohistochemistry and behavioral testing. More recently, we also study the effects of alcohol on cerebellar function and motor adaptation, and the role of deficits in cerebellar associative learning in autism spectrum disorder (ASD).