Research area:
Focus of the team is on neural circuits that mediate the formation and retrieval of associative memories, in particular memory related to drugs of abuse and conditioned-fear. During learning, cellular and molecular changes take place that need to be stabilized in order for memory to be formed and adequately retrieved. Stabilizing memories into neural circuits can also be dysfunctional when they have developed in a maladaptive way. In drug addicts, learned associations between environmental stimuli (i.e. locations where drugs are consumed) and the rewarding effects of drugs of abuse have a crucial role in the maintenance of addictive behaviour. We previously identified a molecular mechanism in the mPFC by which heroin-associated cues elicit relapse, and counteracting this mechanism by molecular intervention reduced relapse vulnerability. Besides an important proof of principle, these experiments pointed to the need of defining the mPFC in- and output circuitry involved, and to further dissect the circuitry adaptations contributing to the expression of drug-associated memories.
Recent evidence indicates that the mPFC is also involved in the expression of conditioned-fear memory, but knowledge on the underlying neuronal circuitry is lacking. Therefore, a second objective is to determine whether appetitive drug-memory and aversive fear-memory share neuronal circuitry mechanisms and adaptations. A detailed understanding this circuitry is crucial for the development of new treatment options for maladaptive forms of memory.

Optogenetics:
Optogenetics is the core technology that the team uses to dissect neuronal circuitries involved in the process of memory formation and retrieval, and to connect molecular plasticity and cellular physiology to behaviour. Optogenetics involves viral-mediated targeting of opsin genes coding for light-sensitive ion channels and ion pumps to genetically-identified neuronal subtypes (e.g. excitatory neurons, GABAergic neurons, dopaminergic neurons etc.) in selected brain regions, thereby allowing light-mediated transient activation or silencing of these neurons in awake behaving animals. Moreover, optic stimulation of opsin-expressing neurons enables the analysis of alterations in synaptic properties between different neuronal subpopulations. Taken together, optogenetics technology, supported by molecular and electrophysiological approaches, allows us to modulate microcircuitries and to study its consequences at the system and behaviour level.

Paradigms and collaborations:
The formation and retrieval of drug-associated memory and conditioned-fear memory is studied using the conditioned place preference (CPP) paradigm, fear-conditioning and the drug self-administration/reinstatement model in collaboration with Sabine Spijker and Taco de Vries. Adaptations at the level of synapse physiology and synaptic proteome are examined in collaboration with Huib Mansvelder and Ka Wan Li.