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Time course of changes in glutamatergic transmission within NTS during CIH exposure and the role of ΔFosB (710.6)
Author(s) -
Wu Qiong,
Mifflin Steve
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.710.6
Subject(s) - fosb , dnqx , medicine , microinjection , endocrinology , biology , chemistry , glutamate receptor , transcription factor , receptor , biochemistry , gene , ampa receptor
ΔFosB is a transcription factor induced by chronic intermittent hypoxia (CIH), a model of the arterial hypoxemia seen in sleep apnea patients. We reported that 7 days of CIH increases the amplitude of mEPSCs recorded in 2 nd order arterial chemoreceptor NTS neurons. We hypothesize that NTS injection of a dominant‐negative construct of ΔFosB (provided by Dr. E. Nestler) to block the function of ΔFosB will block the CIH increase in mEPSC. A brain slice preparation was used to record mEPSCs by whole cell patch clamp in a normoxia group and in rats exposed to CIH of differing durations. mEPSC amplitude in normoxia group and after 1, 3, 5, and 7 days CIH exposure averaged 12.3±0.8 pA (n=12), 19.6±1.3 pA (n=11), 17.5±1.6 pA (n=11), 16.7±1.2 pA (n=21), 18.2±0.8 pA (n=7), respectively (all p<.05 vs. normoxia). 1 day after a 7 day exposure, mEPSC amplitude remained increased (17.5±1.6 pA, n=4), after 3 day recovery mEPSC amplitude was similar to normoxia (12.9±1.0 pA, n=7). AAV‐GFP‐ΔJunD construct was microinjected into NTS to block the function of ΔFosB, then GFP labeled second order NTS neurons were recorded after 1 day and 7 days CIH exposure. ΔFosB inhibition decreased the amplitudes of mEPSCs to normoxia levels in both groups, 13.9±0.6 pA (n=10), 13.0±0.6 pA (n=19), respectively. CIH rapidly enhances the post‐synaptic response to glutamatergic synaptic transmission within the NTS and ΔFosB plays a role in mediating this enhancement. Grant Funding Source : HL088052