Role for subplate neurons in cortical critical periods

Harvard University (Medical School), Boston MA

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Abstract

Subplate (SP) neurons are among the earliest generated neurons of the cerebral cortex, and are present only during the time when cortical organization is highly susceptible to altered neural activity (the critical period). SP neurons have been implicated in visual cortical development because their removal before the critical period leads to disruption of thalamocortical connections and ocular dominance columns in visual cortex. SP removal also increases cortical expression of activity-regulated genes (such as BDNF, trbK and GAD). By controlling cortical activity levels, SP neurons may play a role in cortical development and the critical period. The basic physiology of the subplate and its influence on the cortical circuitry is unknown. The proposed research will investigate in vitro the developmental role of the SP. We will test the hypothesis that SP neurons control or modulate the balance of excitation and inhibition of developing cortex and by that manner influence the critical period. This work will investigate the cortical targets of SP innervation and how the SP modulates thalamocortical activity. Since SP ablation disrupts cortical development and affects cortical gene expression, studies proposed here will test if synaptic efficacy and plasticity are altered. Because inhibition has been shown to be crucial for development, we will also examine if SP ablation affects the maturation cortical inhibition. These studies should further our understanding of SP physiology, and also elucidate how the subplate influences cortical excitability. Thus, this study will provide crucial insight into the function of this transient neuronal population during development and its possible role in regulating the onset and duration of the critical period.