Understanding cortical 'background' activity

Electric and electrical activity of the brain is intricately related to biochemical signalling in the form of neurotransmitter and neuromodulator molecules. Excitatory neurotransmitters can cause ion flow that depolarises the neurons (UP state) eventually initiating action potential, whereas inhibitory neurotransmitters cause hyperpolarisations (DOWN state).

The cerebral cortex produces a very slow (less than once per second or 1 Hz) oscillation between UP and DOWN states independent of external input both in vitro and in vivo. External inputs such as sensory information act on a background of this endogenous activity. Scientists launched the EU-funded project INTRICA (Development and neuromodulation of intrinsic cortical activity) to study the activity during development, evaluate its modulation and investigate it in an animal model of autism.

Team members compared spontaneous cortical UP states in vitro during various stages of development and in two different areas: somatosensory cortex and motor cortex. The activity changed with age in a region-specific manner and, further, extended past the early developmental period into early adulthood. There were periods of pronounced change, indicating massive reorganisation of circuits, and also periods of constancy. Transitions between the developmental phases were in part mediated by changes in inhibitory circuits mediated by the primary inhibitory neurotransmitter receptors (gamma-aminobutyric acid-A (GABA-A) and GABA-B).

Further studies of UP state modulation in genetically modified animals showed that UP state activity is modulated by both high-affinity and low-affinity nicotine (acetylcholinergic) receptors, and that GABA-B inhibition plays a role in the high-affinity nicotinic acetylcholine receptor effects. Researchers are currently investigating potential changes in endogenous activity with autism, having shown a difference in the activity in adult brains that experienced early-life seizures.

INTRICA introduces an in vitro model for the development and maturation of the normal cortical network and sets the stage for the discovery of indicators of disorders manifested as disruptions of the excitation-inhibition balance. Further, the results reveal a direct modulatory role for the high-affinity nicotinic acetylcholine receptors acting through GABA-B receptors. Endogenous background oscillations likely play a critical role in information processing. INTRICA has added some important pieces to the puzzle of how and when this might occur.