Do glia contribute to behaviour? A neuromodulatory review

1. The links between behavioural state, gross electrophysiology and the activity of neurons and astrocytes are reviewed to stimulate interest in the contributions that glia make to behaviour. 2. Behavioural arousal in which neuronal responsivity ("sensitivity") is elevated is also associated with a sustained (0.5-10 sec) potential shift (SPS). 3. There is powerful and accumulating evidence that the SPS is primarily of glial origin. 4. In epilepsy neurons are hyperactive and there is a massive SPS during seizures. In seizure free periods, epileptic animals frequently have elevated arousal responses and increased neuronal sensitivity, indicating that seizures may be due to elevation of the activity of a normally adaptive sensitizing mechanism. 5. The common finding of an astrocytic pathology in epilepsy and the links between arousal, neuronal sensitization, SPSs and seizures implicates a modulatory role for astrocytes in both health and disease. 6. Glia, especially astrocytes, may modulate neuronal responsiveness by regulation of the microenvironment. 7. At the current state of knowledge, regulation of extracellular ionic K+, Ca2+ and neurotransmitter glutamate and GABA seem to be the most important candidates for modulating neuronal sensitivity in arousal and abnormally for seizure genesis. 8. Both in phylogeny and in ontogeny, glia and neurons have intimate associations. 9. The functional astrocytic syncitium is in a prime position to control the ecology of neuronal populations and thereby their activity. 10. The physiology and biochemistry of glia-neuronal interactions offers exciting new prospects for developments in behavioural neuroscience.