Aging and Dementia
My research is almost entirely related to animal research. I first started with ageing studies in which the cognitive performance of aged rats was tested in various behavioural paradigms. I am also interested in models of dementia, although this has changed from old rats and lesion models towards genetic modified mice. Although this line of research has not primary attention I am still doing some studies along this line, if old animals are available. I also studied consequences of life events on cognitive performance of aging rats.
I still have some copies of my PhD thesis in which my studies on aging in rats are described. If you are (still) interested I can send you a copy.
Cognition in Rodents
My interest in the cognitive performance of animals probably originates from my first studies in which I studied the effects of ageing on learning and memory. This topic has intrigued me ever since. Especially, the question of reliable testing of cognitive functions in rodents has been a major topic in my research. For this purpose I have also used other tests to assess other aspects of behaviour of animals in order to scrutinize the changes in cognitive performance. These tests include sensorimotor tests, anxiety tests, depression tests and motivation tests. In addition, within task manipulations are used a manner to dissociate memory and non-memory aspects of behaviour.
In our lab we have several tests that we use to assess cognitive functions in rodents (rats and mice). These tests are used depending on the research questions we have. For the evaluation of drugs on memory we are mainly using an Object Recognition Task. This task has been proven extremely useful for the evaluation of various drugs. At present we are trying to measure EEG characteristics during performance. I also developed a Reaction Time Task for rats. This task has been very useful for different research programs in our laboratory, eg. Parkinson's disease, Huntingdon disease, Stroke. This task has been an excellent tool to dissociate various components of information processing (like in humans), and to dissociate cognitive and motor functions. See blow for other tests that we have available in our lab.
Neurobiology of Learning and Memory
We have been using the Object Recognition task to study the neurobiology of object memory. Several papers have been published in which we studied the role of the cyclic nucleotides cGMP and cAMP. This work has mainly been done with phosphodiesterase (PDE) inhibitors. This work is based on the model of Long-Term Potentiation (LTP). Briefly, our hypothesis is that short-term memory does not involve protein synthesis and is regulated by cGMP (via early LTP). On the other hand, cAMP is involved in long-term memory (late LTP) and is related to the consolidation of memory.
I have always been interested in the neurotransmitter Acetylcholine. In the early eighties this neurotransmitter was regarded as the most important neurotransmitter for learning and memory. My review on this topic is well cited, but not always correctly. I also wrote a review on the drug scopolamine and was published after a long time (Inge Klinkenberg did a great job to finish this one).
Since the use of the acute tryptophan depletion (ATD) method in rats, we have become more interested in the role of 5-HT in memory functions.
5-HT and Behavior
Based on human studies, in which an acute tryptophan depletion method (ATD) was applied, we tried to develop an ATD method for rodents. This was done in collaboration with Dr. Mick Deutz. First we were interested on the effects of ATD on affective behavior (eg. forced swim test, open field). We only observed modest effects of this treatment on affective behavior. On the other hand, object recognition was clearly impaired after ATD. We have shown this now in various studies using different time intervals and in different rat strains. These findings resemble the features of the data in human studies. Effects on mood can only be found in a vulnerable group (eg. FH+ or recovered depressive patients), whereas the effect of ATD on memory performance (especially word learning) is impaired in healthy subjects.
This research line now has two important spin offs:
1) Since the effects of ATD can be found in humans and animals, could this imply that the performance in the object recognition test can predict the effects of treatment in the human word learning test? This has been extended by testing the effects of Sildenafil in humans using the word learning test. Since we have repeatedly found an improved performance in object recognition in rats after Sildenafil treatment, we predict that the same treatment should be able to improve performance in humans.
2) Can we model vulnerability in animal models and does ATD leads to increased depression or anxiety? This is now a topic of a PhD study in which different vulnerability factors are tested experimentally.
At present, my colleague Dr. Jos Prickaerts is developing this ATD method for the application in mice. This has of course many advantages since this would allow the use of this method in different genetic models.
In our laboratories we have various testing available for the behavioral testing of rats and mice. Below you find a list of tests that we use.
- Operant conditioning (eg. attention, (non)matching to position, food motivation)
- Reaction time performance in rats
- Morris water task
- Barnes maze (for mice)
- Object recognition
- Open field
- Social Interaction
- Home cage emergence
- Zero maze
- Forced swimming
- Sucrose intake
- Punished drinking
- Staircase test
EEG and Behavior
Psychopharmacology and ERP
Reaction time and ERP