The brain consists of billions of neurons that are as an ensemble capable of memorizing. It is widely assumed that memories are encoded in the connections between neurons. Thus, new experiences induce connectivity changes in the network, that encode for that memory. However, it remains one of the mysteries of the brain how older memories are protected when new ones are formed.

Cultured networks of cortical neurons on multi electrode arrays provide a suitable platform to study connectivity and plasticity because they facilitate simultaneous recording of neuronal signals, and cells can easily be stimulated electrically or pharmacologically. In several recent studies such cortical networks were stimulated with tetani to induce plasticity. However, other studies showed that the effect of electrical stimulation on connectivity may be ambiguous or hard to reproduce. One of the possible explanations for this difficulty is the balance between activity and connectivity that networks seem to develop, which hampers prediction of the new equilibrium after external stimulation.

A pilot study showed that tetani do affect network connectivity when they are applied for the first time, but not in subsequent applications. We hypothesize that the first tetanus changed connectivity to a new equilibrium that complied with the applied tetanus. Subsequent stimuli had less effect because they already fitted in the current connectivity. If this is true, the network apparently memorizes such a tetanus.

In this project we will verify the earlier observation that connectivity hardly changed upon subsequent tetani. Then, we will apply a second, different tetanus to investigate if a second series of tetani has a similar memory effect.


Research questions include:

§Can we verify the observed memory function? If we cannot reliably reproduce the earlier results, what factor(s) determine the chances on success?

§How fast is a memory formed?

§How does memory formation depend on the time between subsequent tetani?

§Is the observed effect strictly related to tetani, or do single pulses have a similar effect?

§Can we store a second memory in a network?

§Does this interfere with the first memory?

Background publications from earlier projects:

1. Stegenga, J., et al., Phase dependent effects of stimuli locked to oscillatory activity in cultured cortical networks. Biophys J, 2010. 98(11): p. 2452-2458.

2. Stegenga, J., et al., The effect of learning on bursting. IEEE Trans. Biomed. Eng. , 2009. 56(4): p. 1220-1227.

3. le Feber, J., J. Van Pelt, and W. Rutten, Latency related development of functional connections in cultured cortical networks. Biophys. J., 2009. 96(8): p. 3443-3450.

4. le Feber, J., J. Stegenga, and W.L.C. Rutten, The Effect of Slow Electrical Stimuli to Achieve Learning in Cultured Networks of Rat Cortical Neurons. PLoS ONE, 2010. 5(1): p. e8871.

5. le Feber, J., et al., Conditional firing probabilities in cultured neuronal networks: a stable underlying structure in widely varying spontaneous activity patterns. J. Neural Eng., 2007. 4: p. 54-67.

Research themes

From cellular mechanisms to neural circuit behaviour

Principal Investigator tracks

Joost le Feber



People involved

Joost le Feber

Tim Witteveen

Irina Stoyanova

Bettie Klomphaar

Karin Groot Jebbink

Wim Rutten




not yet available

Project website