Network Excitability

Summary

Characteristic of spontaneous activity in the sleeping neocortex are synchronous poly-neuronal bursts. These play an important role in the homeostatic regulation of network excitability. Long-term suppression of these bursts in the cortex leads to hyper excitability what is usually obseverd in the form of epileptic activity patterns. In contrast to the sleep state, the neocortex receives cholinergic input from other nuclei during the more active States (awake or REM sleep), during these states the bursts disappear.

In vitro networks of cortical neurons, cultured on multi electrode arrays (MEAs) are widely used to study neural mechanisms and activity patterns of the brain. Such cultured networks are isolated from the outside world, and almost always exhibit bursts, analogous to the dormant neocortex. If a network is stimulated with acetylcholine (a neurotransmitter that is not synthesized in the cortex itself), firing patterns change to more widespread activity. After prolonged burst suppression, bursting becomes very intense, with very many bursts.

So it seems as if longer periods of little or no activity lead to hyper excitability, while periods of normal or slightly increased activity reduce the network excitabiliy. To test these hypotheses, in this project two pharmacological manipulations are performed: all activity is blocked ~ 24 hours, by means of a sodium channel blocker Tetrodotoxin (TTX). After that, activity is accelerated with carbachol, a synthetic form of the excitatory neurotransmitter acetylcholine. The resulting activity patterns are continuously measured and analyzed, looking at burst frequencies, the ratio of the number of spikes inside/outside bursts and the strength of functional connections.

Research questions are:

·

Do recorded activity patterns confirm the above hypotheses?

·

Does the hyperactivity that typically arises after longer exposure to TTX extend into the cholinergically desynchronized state?

·

Does this period of REM sleep-like cortical activation, in turn affect the activity patterns that we measure after cessation of cholinergic stimulation?

Research

Research questions are:

·

Do recorded activity patterns confirm the above hypotheses?

·

Does the hyperactivity that typically arises after longer exposure to TTX extend into the cholinergically desynchronized state?

·

Does this period of REM sleep-like cortical activation, in turn affect the activity patterns that we measure after cessation of cholinergic stimulation?

Background publications from earlier projects:

1.

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.

2.

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.

3.

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

Funding

internal

People involved

Joost le Feber

Timo Lauteslager

Irina Stoyanova

Bettie Klomphaar

Karin Groot Jebbink

Michela Chiappalone

Michael Corner

Timespan

2010-2012

Publications

1.

Le Feber, J. and M. Corner, Single pulse responses in cultured neuronal networks to describe connectivity, in 5th International IEEE EMBS Conference on Neural Engineering. 2011: Cancun, Mexico. p. 96-99.

2.

le Feber, J., M. Chiappalone, and M. Corner. Lasting Effects of Cholinergic Activation in Developing Cortical Cultures. in FENS. 2010. Amsterdam, the Netherlands.

3.

Chiappalone, M., M. Corner, and J. le Feber, Persistent effects of cholinergic activation in developing cerebral cortex cultures: a model for the role of sleep activity patterns in early development?, in 7th Int Meeting Substrate-Integrated Micro Electrode Arrays, A. Stett, Editor. 2010, BioPro: Reutlingen, Germany. p. 64-65.

Project website