Neonatal Hypoxia-Ischemia Causes Functional Circuit Changes in Subplate Neurons

Aminah Sheikh, Xiangying Meng, Ji Liu, Alexandra Mikhailova, Joseph P.Y. Kao, Patrick S. Mcquillen, Patrick O. Kanold

Research output: Contribution to journalArticlepeer-review

Abstract

Neonatal hypoxia-ischemia (HI) in the preterm human results in damage to subcortical developing white matter and cognitive impairments. Subplate neurons (SPNs) are among the first-born cortical neurons and are necessary for normal cerebral development. While moderate or severe HI at P1 in rats leads to SPN loss, it is unclear if HI, esp. forms not associated with overt cell loss lead to altered SPN circuits. Thus, we used two HI models with different severities in P1 rats. Cauterization of the common carotid artery (CCA) causes a largely transient and thus milder ischemia (HI-Caut) while CCA ligation causes more severe ischemia (HI-Lig). While HI-Lig caused subplate damage, HI-Caut did not cause overt histological damage on the light microscopic level. We used laser-scanning photostimulation (LSPS) in acute thalamocortical slices of auditory cortex during P5-10 to study the functional connectivity of SPNs. Both HI categories resulted in hyperconnectivity of excitatory and inhibitory circuits to SPNs. Thus, alterations on the circuit level are present in the absence of cell loss. Our results show that SPN circuits are uniquely susceptible to HI. Given the key developmental role of SPNs, our results suggest that altered SPN circuits might underlie the abnormal development of cortical function after HI.

Original languageEnglish (US)
Pages (from-to)765-776
Number of pages12
JournalCerebral Cortex
Volume29
Issue number2
DOIs
StatePublished - Feb 1 2019
Externally publishedYes

Keywords

  • auditory cortex
  • complexin-3
  • cortical
  • hypoxia-ischemia
  • neonatal
  • subplate

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Cellular and Molecular Neuroscience

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