Excitatory–inhibitory imbalance in hypoglossal neurons during the critical period of postnatal development in the rat

• Published in: The Journal of physiology Vol. 589; no. 8; pp. 1991 - 2006
• Main Authors: Gao, Xiu‐ping, Liu, Qing‐song, Liu, Qiuli, Wong‐Riley, Margaret T. T.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2011; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Age Factors; Aging; Analysis of Variance; Animals; Animals, Newborn; Brain Stem - cytology; Brain Stem - drug effects; Brain Stem - growth & development; Brain Stem - metabolism; Electric Stimulation; Excitatory Postsynaptic Potentials; gamma-Aminobutyric Acid - metabolism; Glycine - metabolism; Humans; Hypoglossal Nerve - cytology; Hypoglossal Nerve - drug effects; Hypoglossal Nerve - growth & development; Hypoglossal Nerve - metabolism; In Vitro Techniques; Infant; Inhibitory Postsynaptic Potentials; Kinetics; Motor Neurons - drug effects; Motor Neurons - metabolism; Motor Neurons - physiology; Neural Inhibition; Neurons; Neurotransmitter Agents - pharmacology; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Respiratory; Rodents; SIDS; Sudden Infant Death - etiology; Sudden infant death syndrome; Synaptic Transmission - drug effects; Tongue - innervation
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.198945

Non‐technical summary  Previously, our laboratory has reported that within a narrow window toward the end of the second postnatal week in a rat's life, many sudden neurochemical and functional changes occurred that rendered the animal less responsive to decreased oxygen supply. The present study extends these findings to the recordings of single nerve cells and documents that, during this critical period of normal postnatal respiratory network development, the responses to excitation are significantly reduced and those to inhibition are significantly enhanced. Thus, the system is under greater inhibitory influence at this time. These findings may have significant implication for understanding sudden infant death syndrome, whose victims are seemingly normal infants with no known pathologies. The peak incidence of SIDS is not at birth, but between the second and fourth months after birth, a theoretical critical period of postnatal respiratory development.   Hypoglossal motoneurons (HMs) innervate tongue muscles and are critical in maintaining patency of the upper airway during respiration. Abnormalities in HMs have been implicated in sudden infant death syndrome (SIDS) and obstructive sleep apnoea. Previously, we found a critical period in respiratory network development in rats around postnatal day (P) 12–13, when abrupt neurochemical, metabolic and physiological changes occurred. To test our hypothesis that an imbalance between inhibitory and excitatory synaptic transmission exists during the critical period, whole‐cell patch‐clamp recordings of HMs were done in brainstem slices of rats daily from P0 to P16. The results indicated that: (1) the amplitude and charge transfer of miniature excitatory postsynaptic currents (mEPSCs) were significantly reduced at P12–13; (2) the amplitude, mean frequency and charge transfer of miniature inhibitory postsynaptic currents (mIPSCs) were significantly increased at P12–13; (3) the kinetics (rise time and decay time) of both mEPSCs and mIPSCs accelerated with age; (4) the amplitude and frequency of spontaneous EPSCs were significantly reduced at P12–13, whereas those of spontaneous IPSCs were significantly increased at P12–13; and (5) both glycine and GABA contributed to mIPSCs. However, GABAergic currents fluctuated within a narrow range during the first three postnatal weeks, whereas glycinergic ones exhibited age‐dependent changes comparable to those of total mIPSCs, indicating a reversal in dominance from GABA to glycine with development. Thus, our results provide strong electrophysiological evidence for an excitatory–inhibitory imbalance in HMs during the critical period of postnatal development in rats that may have significant implications for SIDS.