In response to changing afferent input, neural pathways may undergo both short term (minutes) and long term (days, weeks) adjustments within the pathway in order to maintain physiological output within an appropriate range. The underlying cellular mechanisms responsible for this homeostatic adaptation may include changes in gene expression and subsequent protein distribution/function. In this study we examine the mechanisms that underlie the long term changes in the central neural component of a cardio-respiratory reflex response to chronic intermittent hypoxia (CIH), a model of sleep apnea. We are using a combination of electrophysiological, molecular and genetic techniques to understand the adaptations (over days/weeks) to CI H that produce sustained changes in chemosensory synaptic transmission in the nucleus of the solitary tract leading to an elevated level of information transfer that is partially restrained by what we propose is a secondary homeostatic adaptation. These changes are thought to contribute to elevated arterial pressure and exaggerated chemoreflexes in CIH. In the first of two years we focus on the mechanisms underlying an increase in spontaneous release of neurotransmitter that occurs after three days of CIH. In the second year we address mechanisms underlying the adaptive response to this exaggerated response and that brings synaptic transmission partially back towards normal. We believe this study is important not only because it provides insight to potential mechanisms for manipulating respiratory and cardiovascular reflexes at specific sites but also because it provides insight to adaptations in neuronal transmission that may be universal in application.
| Tatalovic, Milos; Glazebrook, Patricia A; Kunze, Diana L (2012) Expression of the P/Q (Cav2.1) calcium channel in nodose sensory neurons and arterial baroreceptors. Neurosci Lett 520:38-42 |
| Ramirez-Navarro, Angelina; Glazebrook, Patricia A; Kane-Sutton, Michelle et al. (2011) Kv1.3 channels regulate synaptic transmission in the nucleus of solitary tract. J Neurophysiol 105:2772-80 |
