Heterosynaptic scaling of developing GABAergic synapses: dependence on glutamatergic input and developmental stage.

A proportionality or balance between coactivated excitatory and inhibitory inputs is often observed for individual cortical neurons and is proposed to be important for their functions. This feature of neural circuits may arise from coordinated modulation of excitatory and inhibitory synaptic inputs, a mechanism that remains unknown. Here, in vivo whole-cell recordings from tectal neurons of young Xenopus tadpoles reveals activity-dependent bidirectional modifications of GABAergic inputs. At early developmental stages when GABAergic inputs dominate visually evoked responses, repetitive visual stimulation leads to long-term depression of GABAergic inputs. At later stages when convergent glutamatergic inputs are much stronger, long-term potentiation (LTP) of GABAergic inputs is induced. The polarity of GABAergic plasticity depends on the ratio between the magnitude of coactivated glutamatergic and GABAergic inputs (E/I ratio) to the tectal cell: LTP is induced only when the E/I ratio is above a threshold, and the level of LTP correlates linearly with the logarithm of the E/I ratio. The induction of LTP requires the activation of postsynaptic NMDA receptors, as well as presynaptic TrkB signaling likely through retrograde BDNF (brain-derived neurotrophic factor) and is achieved by overcoming a predominant depression process mediated by NMDA receptors on the presynaptic GABAergic neurons. Our results indicate that the strength of developing GABAergic synapses can be scaled in accordance to coactivated convergent glutamatergic input. This mechanism may contribute to the formation of functional neural circuits with correlated excitatory and inhibitory inputs.