Fine-tuning of pre-balanced excitation and inhibition during auditory cortical development

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Abstract
In order to build a proper and stable representation of the auditory world, neonatal rodents exhibit a significant degree of circuit plasticity, allowing for sensitivity to the pattern of sensory inputs. During this time, neurons construct a receptive field, one that relies upon a particular balance of excitatory and inhibitory inputs, yet it is unknown as to how this balance is formed. Two studies published in this issue of Nature reveal contrasting views as to how the mature system develops. Excitation and inhibition were found to be equally strong upon hearing onset in each study. But whereas Dorrn et al. find evidence for an experience-dependent refinement of inhibition as the receptive fields develop, Sun et al. observed a fine adjustment in the excitatory input strength to produce a shifted balance. Nevertheless, taken together, both studies point towards a fine adjustment of synaptic inputs as the force behind the production of mature receptive fields, as opposed to more radical changes such as input pruning. To build a representation of the auditory world, neuronal circuits in neonatal rodents exhibit plasticity, allowing sensitivity to the pattern of sensory inputs. At this time, neurons construct a receptive field, which relies on a balance of excitatory and inhibitory inputs. Here, excitation and inhibition were found to be co-tuned upon hearing onset, but later an adjustment in the excitatory input strength occurred. Thus a fine adjustment in synaptic inputs, rather than more radical changes such as input pruning, may refine mature receptive fields. Functional receptive fields of neurons in sensory cortices undergo progressive refinement during development1,2,3,4. Such refinement may be attributed to the pruning of non-optimal excitatory inputs, reshaping of the excitatory tuning profile through modifying the strengths of individual inputs, or strengthening of cortical inhibition. These models have not been directly tested because of the technical difficulties in assaying the spatiotemporal patterns of functional synaptic inputs during development. Here we apply in vivo whole-cell voltage-clamp recordings to the recipient layer 4 neurons in the rat primary auditory cortex (A1) to determine the developmental changes in the frequency–intensity tonal receptive fields (TRFs) of their excitatory and inhibitory inputs. Surprisingly, we observe co-tuned excitation and inhibition immediately after the onset of hearing, suggesting that a tripartite thalamocortical circuit with relatively strong feedforward inhibition is formed independently of auditory experience. The frequency ranges of tone-driven excitatory and inhibitory inputs first expand within a few days of the onset of hearing and then persist into adulthood. The latter phase is accompanied by a sharpening of the excitatory but not inhibitory frequency tuning profile, which results in relatively broader inhibitory tuning in adult A1 neurons. Thus the development of cortical synaptic TRFs after the onset of hearing is marked by a slight breakdown of previously formed excitation–inhibition balance. Our results suggest that functional refinement of cortical TRFs does not require a selective pruning of inputs, but may depend more on a fine adjustment of excitatory input strengths.