Subplate Neurons Regulate Maturation of Cortical Inhibition and Outcome of Ocular Dominance Plasticity

Abstract

Synaptic plasticity during critical periods of development requires intact inhibitory circuitry. We report that subplate neurons are needed both for maturation of inhibition and for the proper sign of ocular dominance (OD) plasticity. Removal of subplate neurons prevents the developmental upregulation of genes involved in mature, fast GABAergic transmission in cortical layer 4, including GABA receptor subunits and KCC2, and thus prevents the switch to a hyperpolarizing effect of GABA. To understand the implications of these changes, a realistic circuit model was formulated. Simulations predicted that without subplate neurons, monocular deprivation (MD) paradoxically favors LGN axons representing the deprived (less active) eye, exactly what was then observed experimentally. Simulations also account for published results showing that OD plasticity requires mature inhibition. Thus, subplate neurons regulate molecular machinery required to establish an adult balance of excitation and inhibition in layer 4, and thereby influence the outcome of OD plasticity.

The determination of projection neuron identity in the developing cerebral cortex

“…The advent of retrograde tracing techniques and intracellular dye injections revealed that, as a general rule, neurons in the upper layers 2 and 3 tend to form corticocortical connections, including projections to the contralateral hemisphere across the corpus callosum, whereas neurons in layers 5,6, and the subplate are the source of subcortical projections to targets that include the spinal cord, pons, midbrain, and thalamus. Neurons in layers 1 and 4 extend axons locally within the cortex.…”

“…The upper preplate, which is known during development as the marginal zone, is populated by Cajal-Retzius neurons, of which many or most are derived from a region known as the cortical hem (located near the hippocampal anlage) and then migrate tangentially to populated the neocortex [4,5]. The deeper domain of the preplate becomes the subplate, a largely transient zone of neurons that plays important roles in axon targeting during development [6]. Within the cortical plate, neurons of the deepest layers (6 and 5) are generated at the earliest stages, followed by neurons of layers 4, 3 and 2.…”

Electrical synapses formed by connexin36 regulate inhibition- and experience-dependent plasticity

“…OD ratio was computed as contra/ipsi VEP amplitude ratio. OD plasticity experiments using Arc and qRT-PCR were carried out as described (11,(29)(30)(31)48). ANOVA, t test, or Wilcoxon was used for statistical comparisons, and P < 0.05 was considered significant.…”

Parsing out the embryonic origin of subplate cell-type diversity

“…Because SNs have been implicated in circuit assembly (8,9), it would be interesting to perform diphtheria toxin-mediated ablation of RMTW cells and assess how this manipulation affects the assembly of cortical cytoarchitecture. The report by Pedraza et al (11) provides a significant advancement to our current knowledge of early neuronal subtype diversity and paves the way to ask further fundamental questions in an effort to unravel the logic underlying wiring of the brain.…”

“…Remarkably, the dorsolateral geniculate nucleus becomes uncoupled from the visual cortex upon SN ablation, resulting in marked impairment of sensory information processing (8). In addition to a role in the maturation of glutamatergic activity, SNs regulate the maturation of GABAergic innervation by controlling the expression of the chloride cotransporter KCC2 (9). Finally, SNs have been implicated in regulating the proper assembly of cortical columns (10).…”