Developmental maturation of excitation and inhibition balance in principal neurons across four layers of somatosensory cortex.
In adult cortices, the ratio of excitatory and inhibitory conductances (E/I ratio) is presumably balanced across a wide range of stimulus conditions. However, it is unknown how the E/I ratio is postnatally regulated, when the strength of synapses are rapidly changing. Yet, understanding of such a process is critically important, because there are numerous neuropsychological disorders, such as autism, epilepsy and schizophrenia, associated with disturbed E/I balances. Here we directly measured the E/I ratio underlying locally induced synaptic conductances in principal neurons from postnatal day 8 (P8) through 60. We found that (1) within each developmental period, the E/I ratio across four major cortical layers was maintained at a similar value under wide range of stimulation intensities; and (2) there was a rapid developmental decrease in the E/I ratio, which occurred within a sensitive period between P8 to P18 with exception of layer II/III. By comparing the excitatory and inhibitory conductances, as well as key synaptic protein expressions, we found a net increase in the number and strength of inhibitory, but not excitatory synapses, is responsible for the developmental decrease in the E/I ratio in the barrel cortex. The inhibitory markers were intrinsically co-regulated, gave rise to a sharp increase in the inhibitory conductance from P8 to P18. These results suggest that the tightly regulated E/I ratios in adults cortex is a result of drastic changes in relative weight of inhibitory but not excitatory synapses during critical period, and the local inhibitory structural changes are the underpinning of altered E/I ratio across postnatal development.
Department of Zoology and Physiology, University of Wyoming, Laramie, WY 82071, USA.
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D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000254:growth & development* / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials; D051379:Mice; D008822:Mice, Transgenic; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D013997:Time Factors; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D014633:Valine