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Research Portfolio


A new approach to the treatment of absence seizures


Grant round winners 2012

grant amount:

£149,827, over 36 months

lead investigator:

Professor Vincenzo Crunelli



University of Cardiff


Epileptic seizures occur when the neurons of the brain are hyperexcitable. This is usually prevented by the maintenance of a fine balance between excitation and inhibition in the brain, which is brought about by molecules known as neurotransmitters (NTs). NTs allow neurons to communicate with each other and can either be excitatory or inhibitory. An excitatory NT will trigger the subsequent neuron to fire, whilst an inhibitory NT will suppress it. The main excitatory and inhibitory NTs in the brain are known as glutamate and GABA respectively. Serotonin (5-HT) is another NT that is able to modulate the activity of the other two.

In generalised epilepsies (GEs), seizures involve the entire brain, as opposed to originating in a particular region (as in focal/partial epilepsy). The causes of GEs are often not known, and in these cases they are said to be idiopathic (IGEs). Absence seizures (ASs) are generalised seizures that are characterised by a sudden interruption of activity, transient loss of consciousness and a blank stare. They are a feature of many IGEs, yet their underlying mechanisms are not fully understood and anti-epileptic drug (AED) treatment is only effective in 50-80% of people affected.

The thalamus is a structure located in the centre of the brain, which relays nerve signals to and from the cortex (the folded surface of the brain). It also helps to regulate sleep, consciousness and alertness, and it is thought to be important in AS generation.

The Study

Professor Vincenzo Crunelli and colleagues, at the University of Cardiff, have recently been awarded £149,827, over 36 months, to carry out a project entitled ‘Serotonergic modulation of absence seizures: focus on tonic GABA inhibition in the thalamus’, in which they will further explore the role of the thalamus in AS.

In a previous study, the group discovered a novel form of GABA activity called ‘tonic GABAA inhibition’ was increased in the thalamus of animal models of absence epilepsy, and this increase in tonic GABAA inhibition was necessary for absence seizures to occur. In principle, it should be possible to target and block GABAA inhibition with drugs and prevent seizures from occurring; however existing therapies would not be selective enough and would also disrupt the ‘normal’ GABA inhibition.


The current project will use the latest techniques to confirm whether thalamic 5-HT is also abnormal in models of absence epilepsy and, if so, whether it can be used to modulate tonic GABAA inhibition indirectly. If successful, this could potentially lead to the development of more effective anti-absence drugs in the future.