Developmental nicotine exposure disrupts dendritic arborization patterns of hypoglossal motoneurons in the neonatal rat

Abstract

Maternal smoking or use of other products containing nicotine during pregnancy can have significant adverse consequences for respiratory function in neonates. We have shown, in previous studies, that developmental nicotine exposure (DNE) in a model system compromises the normal function of respiratory circuits within the brainstem. The effects of DNE include alterations in the excitability and synaptic interactions of the hypoglossal motoneurons, which innervate muscles of the tongue. This study was undertaken to test the hypothesis that these functional consequences of DNE are accompanied by changes in the dendritic morphology of hypoglossal motoneurons. Hypoglossal motoneurons in brain stem slices were filled with neurobiotin during whole-cell patch clamp recordings and subjected to histological processing to reveal dendrites. Morphometric analysis, including the Sholl method, revealed significant effects of DNE on dendritic branching patterns. In particular, whereas within the first 5 postnatal days there was significant growth of the higher-order dendritic branches of motoneurons from control animals, the growth was compromised in motoneurons from neonates that were subjected to DNE.

Influence of developmental nicotine exposure on glutamatergic neurotransmission in rhythmically active hypoglossal motoneurons

“…The increased AMPA-mediated quantal size in XIIMNs from DNE animals may help explain the previously reported heightened response to microinjection of AMPA or glutamate into the hypoglossal motor nucleus (Jaiswal et al, 2013), the concomitant reduction in glutamate receptor expression (Jaiswal et al, 2013) and the reduction in the size and complexity of the dendritic tree in XIIMNs of DNE animals (Powell et al, 2016). The functional significance of these observations has yet to be established but our working hypothesis is that the increased glutamate release and reduced cell size leads to hyperexcitability of XIIMNs (Jaiswal et al, 2013; Pilarski et al, 2011), and the reduction in transmitter receptor expression is a form of homeostatic plasticity that helps to restore normal excitability.…”

“…Furthermore, bath application activates all postsynaptic sites simultaneously. We have recently reported that DNE leads to a significant alteration of XIIMN dendritic branching (Powell et al, 2016). Therefore, there may be rearrangement of synaptic locations relative to the cell body, or changes in the subtypes or density of glutamatergic receptors at a subset of postsynaptic sites that lead to increased mEPSC amplitude but not increased overall response of the XIIMNs to bath application of agonists.…”

Changes in the Morphology of Hypoglossal Motor Neurons in the Brainstem of Developing Rats

“…Because the proportions (percentage of the total data represented by each distribution) of the two distributions are not constant across the three age groups, the mixed distributions appeared to best characterize size shift—more neurons with larger soma—with increasing age. One possible explanation for this second distribution is that these neurons may be growing faster, earlier and the loss of this subgroup could relate to a delay or reduced rate of development as has been suggested for perinatal nicotine exposure (Powell et al ., ).…”

“…This is one of the first studies to demonstrate that the sensitive period from P10 through P13 represents not only a window of time in which abrupt changes occur, but a vulnerable window in which heightened susceptibility to infection can occur. Another recent study of perinatal nicotine exposure showed morphological changes in XII MNs for P0–P4 but did not extend to P10–P13 (Powell et al ., ). Thus, there are very few, if any studies that have examined respiratory or related phenomena for perinatal nicotine exposure or maternal inflammation during P10–P13.…”

Plasticity in respiratory motor neurons in response to reduced synaptic inputs: A form of homeostatic plasticity in respiratory control?

“…Nicotine is a powerful neuroteratogen, resulting in an array of developmental abnormalities, including in neurons underlying breathing (Pilarski et al, 2011; Jaiswal et al, 2013, 2016). Developmental nicotine exposure disrupts normal growth of hypoglossal motor neurons (Powell et al, 2016) and increases their excitability (Pilarski et al, 2011, Jaiswal et al, 2013, Jaiswal et al, 2016). However, these changes are counterbalanced by decreased glutamatergic (Jaiswal et al, 2013) and enhanced GABAergic synaptic transmission (Jaiswal et al, 2016) between brainstem neurons generating respiratory rhythm and pattern and hypoglossal motor neurons.…”