Stability of neural circuit function

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The nervous system must adapt and change to allow us to learn new tasks or to cope with injury and disease. One significant area of change is the amount of excitation neurons are exposed to. All neurons become 'wired' together in circuits that control our behaviours and potential to learn. These connections, termed synapses, are highly dynamic and can rapidly change their how strongly they activate partner neurons. These changes, when summed, have the potential to either leave a target neuron devoid of excitation or, by contrast, saturated. Either extreme can push neural circuits towards destabilisation and may result in diseases such as epilepsy. To guard against such extremes, neurons have developed homeostatic mechanisms to allow them to adjust how they respond to synaptic excitation. If excitation becomes too low, neurons boost their output by firing more than normal numbers of action potentials. If excitation becomes too great, these same neurons respond by reducing their action potential firing. It is, therefore, implicit that individual neurons have an inbuilt 'sense' of what is an appropriate level of activity. How such a reference-level develops and what the molecular components of the system are remains to be determined. We have identified a novel period in early neural circuit formation where manipulation of neural activity is sufficient to permanently change functional stability of mature neural circuits. We hypothesize that this period is required for the establishment of suitable activity-reference points that will form the foundation of on-going homeostatic mechanisms. Our studies utilise the fruitfly because its genome is fully sequenced and because it provides a simple model for the human nervous system.