Systems neuroscienceSerotonin-induced in vitro long-term facilitation exhibits differential pattern sensitivity in cervical and thoracic inspiratory motor output
Section snippets
Brainstem–spinal cord preparations
The University of Wisconsin Institutional Animal Care and Use Committee approved all experimental procedures. All experiments conformed to International Guiding Principles for Biomedical Research Involving Animals as established by the Council for International Organizations of Medical Sciences. Statistical calculations were performed during the study to minimize the number of animals used to obtain valid scientific results. Sprague–Dawley (Colony 217, Harlan Sprague Dawley, Inc., Indianapolis,
Results
To avoid studies on unstable preparations, criteria were established to quantify the stability of the inspiratory burst frequency. If the inter-burst period increased to greater than three standard deviations above the average inter-burst period during baseline, it was taken as an indication that the preparation was not stable, and data from these experiments were excluded from analysis (23 of 49 preparations were excluded). The average inter-burst period at the beginning and end of experiments
Discussion
To our knowledge, this is the first demonstration of spinal 5-HT-induced LTF in vitro. Spinal 5-HT receptor activation, without hypoxia, is sufficient to induce LTF in both cervical and thoracic respiratory motor output in vitro. Although the magnitude of LTF was similar in cervical and thoracic motoneurons following episodic spinal 5-HT application, there were profound differences in pattern sensitivity between these motor outputs. Whereas cervical LTF exhibited pattern sensitivity similar to
Conclusions
5-HT is sufficient to elicit LTF in spinal respiratory motor output in vitro. The LTF magnitude is relatively similar between these motor pools. However, differential pattern sensitivity between cervical and thoracic LTF may provide a novel and highly useful model to study the mechanistic basis of pattern sensitivity in respiratory plasticity, or other important forms of pattern sensitivity in both invertebrate and vertebrate nervous systems (Pittenger and Kandel, 2003).
Acknowledgments
We would like to thank Dr. Mark Brownfield for the generous gift of the 5-HT2A and 5-HT7 antibodies. This work was supported by NIH 69064 and HL 080209. M. R. L.-B. was supported by an NIH training grant (NRSA) GM007507.
References (32)
- et al.
Endogenous 5-HT(1/2) systems and the newborn rat respiratory controlA comparative in vivo and in vitro study
Respir Physiol Neurobiol
(2004) - et al.
Statics of the respiratory system in newborn mammals
Respir Physiol
(1980) - et al.
Long term facilitation of phrenic motor output
Respir Physiol
(2000) - et al.
Prolonged augmentation of respiratory discharge in hypoglossal motoneurons following superior laryngeal nerve stimulation
Brain Res
(1991) - et al.
Depth profiles of pH and PO2 in the isolated brain stem-spinal cord of the neonatal rat
Respir Physiol
(1993) - et al.
Episodic but not continuous hypoxia elicits long-term facilitation of phrenic motor output in rats
J Physiol
(2000) - et al.
Phrenic long-term facilitation requires spinal serotonin receptor activation and protein synthesis
J Neurosci
(2002) - et al.
BDNF is necessary and sufficient for spinal respiratory plasticity following intermittent hypoxia
Nat Neurosci
(2004) - et al.
An in vitro model of 5-HT-induced spinal respiratory long-term facilitation (LTF) reveals differences between cervical and thoracic motoneurons2005 Experimental biology abstracts
FASEB J
(2005) - et al.
Synaptic activity-independent persistent plasticity in endogenously active mammalian motoneurons
Proc Natl Acad Sci U S A
(2004)