Preterm Birth Impedes Structural and Functional Development of Cerebellar Purkinje Cells in the Developing Baboon Cerebellum.

Tara Barron,Jun Hee Kim

doi:10.3390/brainsci10120897

Abstract

Human cerebellar development occurs late in gestation and is hindered by preterm birth. The fetal development of Purkinje cells, the primary output cells of the cerebellar cortex, is crucial for the structure and function of the cerebellum. However, morphological and electrophysiological features in Purkinje cells at different gestational ages, and the effects of neonatal intensive care unit (NICU) experience on cerebellar development are unexplored. Utilizing the non-human primate baboon cerebellum, we investigated Purkinje cell development during the last trimester of pregnancy and the effect of NICU experience following premature birth on developmental features of Purkinje cells. Immunostaining and whole-cell patch clamp recordings of Purkinje cells in the baboon cerebellum at different gestational ages revealed that molecular layer width, driven by Purkinje dendrite extension, drastically increased and refinement of action potential waveform properties occurred throughout the last trimester of pregnancy. Preterm birth followed by NICU experience for 2 weeks impeded development of Purkinje cells, including action potential waveform properties, synaptic input, and dendrite extension compared with age-matched controls. In addition, these alterations impact Purkinje cell output, reducing the spontaneous firing frequency in deep cerebellar nucleus (DCN) neurons. Taken together, the primate cerebellum undergoes developmental refinements during late gestation, and NICU experience following extreme preterm birth influences morphological and physiological features in the cerebellum that can lead to functional deficits.

Highlights

Preterm birth is prevalent even in developed countries, as nearly 10% of infants were born preterm in the US in 2017 [1]
During the last trimester of pregnancy, the cerebellum became larger in size of overall structures with an increased surface area and folial complexity as described in human cerebellum [7,18,19] (Figure 1b)
Morphological development of baboon cerebellum duringduring the lastthe trimester of the pregnancy

Summary

Introduction

Preterm birth is prevalent even in developed countries, as nearly 10% of infants were born preterm in the US in 2017 [1]. After pre-term birth, infants continue their development in the highly stimulatory environment of the neonatal intensive care unit (NICU), rather than protected in the womb. Survival of preterm infants has increased due to improved treatment in the NICU, preterm birth still results in deficits in neurodevelopment, leading to long-term disabilities. Individuals born prematurely have been shown a reduction in cerebellar size associated with hemorrhage [3], infarction [4], or, commonly, underdevelopment [5,6,7]. Reduced cerebellar size caused by preterm birth can lead to cognitive, neuropsychological, and motor function deficits [5,8] and can persist into adulthood [8]

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Results

Conclusion