Presented at the Neonatal Society 2016 Autumn Meeting.
Cross CM, Luyt K, Ashby MC
Department of Physiology, Pharmacology and Neuroscience, University of Bristol
Background: The preterm period coincides with rapid neurological development, during which neural migration and synaptogenesis result in the maturation of the thalamocortical pathways (1). As such it is postulated that premature birth results in disruptions in this development, affecting the connectivity of the infant brain, contributing to the neurological deficits seen clinically. This study uses a mouse model of prematurity to investigate the development of the sensorimotor pathways, at a synaptic, cellular and behavioural level.
Methods: Premature birth was induced in C57BL/6 female mice with a subcutaneous injection of the progesterone receptor antagonist RU486 (Mifepristone). Experiments were carried out on offspring during the first 3 postnatal weeks. Whole-cell patch clamp recordings of stellate neurons in acute barrel cortex slices were used to measure neuron membrane properties, excitability and miniature excitatory post-synaptic currents (mEPSCs). Anatomical development of the barrel cortex was assessed histologically using cytochrome oxidase (CO) staining. The development of reflexive sensorimotor behaviours were assessed with a battery of behavioural tests.
Results: RU486 successfully induced preterm birth (mean gestation lengths: preterm = 18days±1.4 hours (n=29); control = 19days 12±17hrs (n=21). P < 0.0001; two-tailed T-test)). Membrane properties and excitability of stellate cells showed marked developmental changes and the frequency of mEPSCs in the barrel cortex increased with age. However we found no differences between the development of these features in preterm and term pups. Assessment of thalamocortical neuron migration using CO staining showed that preterm and term pups followed the same developmental time course, with distinct barrels being visible by the end of the first postnatal week. Pups ability to complete tasks requiring sensorimotor coordination, such as righting reflex and cliff aversion, and reflexive sensory behaviours such as whisking, improved during the first 3 postnatal weeks, with preterm and term pups developing at the same rate. At weaning (postnatal day 21) open-field testing showed no differences in mobility or exploratory and anxiety behaviours in premature pups compared to controls.
Conclusion: Premature birth in mice raised in a normal environment with their dam does not alter the developmental trajectory of the sensorimotor pathway, on a synaptic, cellular or behavioural level.
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1. Kanold PO (2010), Luhmann HJ. The subplate and early cortical circuits. 33:23–48