Neurobiology of memory

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My main research topic is on the neurobiology of memory. Examples of questions I try to answer are 'What type of memory process is regulated by acetylcholine or serotonin?' and 'To what extent do acetylcholine and serotonin interact in their effect on memory?'. But in our research group, we are also interested in the role of dopamine (see dopamine biomarkers section) and glutamate in memory. One of my PhD students, Inge Klinkenberg, assesses amongst others the role of the muscarinic receptor in episodic memory. We have used biperiden, an M1 antagonist, in a couple of studies and found that it significantly impairs short- and long-term memory (see figure below).

In my VENI project, I have studied the interaction between biperiden and other medication such as citalopram (a selective serotonin re-uptake inhibitor) and rivastigmine (a cholinesterase inhibitor). Also the interaction between acute tryptophan depletion, which decreases serotonin turnover in the brain, and biperiden was examined. And finally, we combined citalopram and rivastigmine in one study. Generally, we found that there is no interaction between acetylcholine and serotonin treatments on the behavioural level (see figure above). 

About a year ago, we (Jos Prickaerts as PI, Arjan Blokland, Frans Verhey, and me) received a grant by ZonMW/NWO to study the effects of PDE4 inhibition on memory in young and elderly participants. By inhibiting PDE4, inactivation of some second messengers is prevented, leading to enhanced signal transduction. Animal research has shown that PDE4 inhibition improves memory and we are going to determine whether the effects are the same in humans.

Finally, the effects of remifentanil, a mu-opioid receptor agonist, are studied in collaboration with Sinikka Munte, Seppo Kahkonen, and Eija Kalso from Helsinki University Central Hospital and Conny Quaedflieg from Maastricht University. With this research group, we also determine the memory impairments found in chronic pain patients. We found that remifentanil affects the mismatch negativity, which reflects sensory memory processes. We are still recruiting participants for our chronic pain project.