Subplate neurons and their role in the functional maturation of the brain

dc.contributor.advisorKanold, Patrick Oen_US
dc.contributor.authorSheikh, Aminahen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.description.abstractNormal brain development is crucial for the proper maturation of neural circuits and cognitive functioning. White matter brain injury during development results in disruption of normal brain maturation and consequently increases risk of developing disorders such as epilepsy and cerebral palsy. Crucial for the proper development of thalamocortical circuits are a transient population of neurons in the developing subcortical white matter of the brain referred to as subplate neurons (SPNs). SPNs are among the first cortical neurons to be born and are necessary for normal functional development of the cerebral cortex. This dissertation begins by studying the effect of SPN removal in the neonatal rat somatosensory cortex (S1). After subplate ablation in the S1 barrel region, we find that removal of SPNs prevents the development of the barrel field in L4, and in vitro recordings reveal that thalamocortical inputs to layer 4 neurons are weak. This dissertation then progresses to investigating the effects of a more clinically relevant and common brain injury among humans, neonatal hypoxia-ischemia (HI), which causes brain damage specific to different brain structures over development. In the preterm human, HI results in damage to subcortical developing white matter, referred to as periventricular leukomalacia (PVL). From other studies we know that HI can damage SPNs however, it is unclear how HI and its differing severities alters SPN circuits. This dissertation uses a rat model of HI in which either mild or moderate HI was induced at postnatal day (P)1. To investigate the functional synaptic connectivity changes of SPNs and layer 4 neurons in both injury categories, this dissertation also uses laser-scanning photostimulation (LSPS) combined with whole-cell patch clamp recordings in acute thalamocortical slices of rat A1 over development. Our results suggest that SPNs are uniquely susceptible to HI and that HI causes a rearrangement of SPN circuits. This leads to abnormal cortical function observed after HI. Results from these studies help fill in crucial gaps in the understanding of not only how important SPNs are in the proper development of multiple sensory regions, but also how vulnerable they are to hypoxic-ischemic brain injury.en_US
dc.titleSubplate neurons and their role in the functional maturation of the brainen_US


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