Inhibition to Excitation Ratio Regulates Visual System Responses and Behavior in vivo

The balance of inhibitory to excitatory synaptic inputs is thought to control information processing and behavioral output of the CNS. We tested the effects of decreased or increased inhibition/excitation (I/E) ratio on visual circuit function and visually-guided behavior in Xenopus tadpoles. We decreased inhibitory synaptic transmission in tectal neurons by knocking down the GABA(A) receptor γ2 subunit or by expressing a peptide, called ICL, that interferes with anchoring GABA(A)R at synapses. Recordings of mIPSCs and mEPSCs showed that these treatments selectively decreased mIPSCs frequency, resulting in a ~50% decrease in the ratio of inhibitory to excitatory synaptic input. ICL expression and γ2 subunit knockdown also decreased the I/E ratio of optic nerve evoked synaptic responses. We recorded visually-evoked responses from tectal neurons and found that decreasing the synaptic I/E ratio increased the variance of first-spike latency, increased recurrent activity in the tectal circuit, enlarged spatial receptive fields and lengthened the synaptic integration window. We used the benzodiazepine, diazepam, to increase inhibitory synaptic activity. Diazepam increased optic nerve evoked inhibitory transmission, but did not affect evoked excitatory currents, resulting in ~30% increase in I/E ratio. Increasing the I/E ratio with diazepam decreased the variance of first-spike latency, decreased spatial receptive field size and lengthened temporal receptive fields. Sequential recordings of spikes and excitatory and inhibitory synaptic inputs to the same visual stimuli demonstrated that decreasing or increasing I/E ratio disrupted input/output relations. We assessed the effect of altered I/E ratio on a visually-guided behavior that requires the optic tectum. Increasing and decreasing I/E in tectal neurons blocked the tectally-mediated visual avoidance behavior. Because ICL expression, γ2-subunit knockdown and diazepam did not directly affect excitatory synaptic transmission, these results indicate that decreasing or increasing the I/E ratio disrupts visual system responses and visually-guided behavior.