Abrupt changes in pentobarbital sensitivity in preBötzinger complex region, hypoglossal motor nucleus, nucleus tractus solitarius, and cortex during rat transitional period (P10–P15)

Abstract

On postnatal days P10–P15 in rat medulla, neurotransmitter receptor subunit composition shifts towards a more mature phenotype. Since medullary GABAARs regulate cardiorespiratory function, abrupt alterations in GABAergic synaptic inhibition could disrupt homeostasis. We hypothesized that GABAARs on medullary neurons become more resistant to positive allosteric modulation during P10–P15. Medullary and cortical slices from P10–P20 rats were used to record spontaneous action potentials in pre-Botzinger Complex (preBötC-region), hypoglossal (XII) motor nucleus, nucleus tractus solitariius (NTS), and cortex during exposure to pentobarbital (positive allosteric modulator of GABAARs). On P14, pentobarbital resistance abruptly increased in preBötC-region and decreased in NTS, but these changes in pentobarbital resistance were not present on P15. Pentobarbital resistance decreased in XII motor nucleus during P11–P15 with a nadir at P14. Abrupt changes in pentobarbital resistance indicate changes in GABAergic receptor composition and function that may compensate for potential increased GABAergic inhibition and respiratory depression that occurs during this key developmental transitional period.

Lung-injury depresses glutamatergic synaptic transmission in the nucleus tractus solitarii via discrete age-dependent mechanisms in neonatal rats

“…There is considerable evidence P11–15 represents a TP for breathing control in the rat-pup. Firstly, during this period excitatory and inhibitory transmission systems within several brainstem respiratory sites (including the nTS) undergo abrupt changes towards adult neuronal expression levels (Wong-Riley and Liu, 2008; Liu and Wong-Riley, 2010a, 2012a, 2013; Turner and Johnson, 2015; Bavis and MacFarlane, 2017), which are similar to TPs in other CNS sites (Kumar et al, 2002; Tyzio et al, 2007; Brill and Huguenard, 2008; Roberts et al, 2009; Isoo et al, 2016). Secondly, the ventilatory responses to acute hypoxia or hypercapnia become transiently blunted between P12 and P15 and exposure to chronic hypoxia during this period can prolong the hypoxic insensitivity; this suggests the TP may be an important step towards the development of some ventilatory functions (Liu et al, 2009; Teran et al, 2014; Bavis and MacFarlane, 2017).…”