Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC130
Depressed TS-evoked glutamatergic transmission on NTS neurons of CIH rats is due to reduced number of functional synapses
C. L. Almado1, B. H. Machado1, R. M. Leão1
1. Physiology, School of Medicine of Ribeir
Chronic intermittent hypoxia (CIH) induces several changes in the cardiovascular and respiratory neural control, including reduction in the afferent synaptic transmission on nucleus tractus solitarii (NTS) neurons. Here we studied the mechanisms involved in this reduction in NTS neurons of CIH rats. Male rats (21 days old) were exposed to 10 days of CIH, and after this period whole-cell glutamatergic synaptic currents were recorded in neurons within caudal and intermediate NTS in horizontal brainstem slices at room temperature. Tractus Solitarii (TS)-evoked glutamatergic post-synaptic currents (eEPSCs) were obtained by TS electrical stimulation in the presence of GABAA receptor antagonist bicuculline. The neurons were classified according to the standard deviation (SD) of latency for eEPSCs, as 2nd-order neurons (latency SD<250 µs) and putative higher-order neurons (latency SD>250 µs). CIH selectively reduced the amplitude of eEPSCs in 2nd-order neurons (325±22 vs. 187±10 pA, n=58; P<0.0001) but did not affect the eEPSC amplitudes of putative higher-order NTS neurons (102±19 vs. 113±16 pA, n=20). Concerning the mechanisms of eEPSC reduction in 2nd-order neurons CIH did not affect the short-term depression of the non-NMDA EPSCs, suggesting the absence of changes in release probability. This evidence is supported by the lack of changes in mEPSC frequency as well as in the number of failures of EPSCs evoked in cadmium (Cd2+) or low calcium experiments (0.2 mM). In addition, a post-synaptic effect of CIH is ruled out because the half-width of eEPSCs, the amplitude of mEPSCs and the amplitude of EPSCs evoked in the presence of low Ca2+, Cd2+ or strontium [Sr2+ (asynchronous eEPSCs)] were similar in both groups. However, the total number of asynchronous eEPSCs recorded in the presence of 2 mM of Sr2+ was significantly reduced after CIH suggesting a decrease in the number of functional synapses. A minimal stimulation protocol of the TS showed that the amplitude of the putative single-fiber eEPSCs was slightly diminished after CIH (17.6±0.6 vs. 16±0.5 pA, n=22, P<0.05) while the estimated number of afferent fibers was greatly reduced (24±2 vs. 12±1 fibers, n=22, P<0.0001). These findings support the concept that CIH selectively depresses TS-evoked glutamatergic synaptic transmission on 2nd-order NTS neurons by a reduction in the number of functional synapses, probably due to a plastic homeostatic adaptation to the overexcitation of visceral afferents inputs in CIH rats.
Where applicable, experiments conform with Society ethical requirements