Figure 7. Restoring excitation:inhibition (E:I) balance during the critical period (CP) rescues seizure phenotype caused by a genetic mutation.

(A) The para^bss (bss) mutation causes lifelong neural hyperactivity, which is evident in a long duration of recovery from seizure when compared to wild-type controls (Canton-S). This recovery can be rescued by balancing the hyperactivity present with inhibition provided by sufficiently strong stimulation of chordotonal (ch) neurons, during the CP (bss + 80 dB). Weaker stimulation of the ch neuron-mediated inhibition provides intermediate phenotypes (bss + 60 dB, bss + 40 dB) that suggest the function of the mature network reflects the sum of excitatory and inhibitory activity during the CP. (B) para^bss raised at 21°C experience less excitation than those raised at 25°C (e.g. in A) during development, and demonstrate a reduced seizure phenotype compared to the latter. This phenotype is completely rescued by 40 dB stimulation of ch neurons (vs. 80 dB at 25°C (A)), which supports the idea that it is a balanced sum of excitatory and inhibitory activity during the CP, that enables normal mature network function. Similarly, exposing para^bss raised at 21°C to 80 dB vibration during the CP results in a significant increase in seizure duration. We hypothesise that at this temperature inhibition provided by ch neuron activity is greater than the increase in excitation resulting from the para^bss mutation.