Hypercapnic acidosis (HA) increases glutamatergic but decreases GABAergic input to chemosensitive neurons from the caudal nucleus tractus solitarius (cNTS) from neonatal rats

Abstract

We examined the modulation of synaptic input by HA in cNTS neurons. Whole‐cell patch clamp was used to measure the postsynaptic currents in brainstem slices from neonatal rats. The frequency of spontaneous excitatory postsynaptic currents (sEPSC) was increased from 1 to 1.6 Hz (p=0.02; n=11) by HA (15% CO2) and from 1.3 to 2 Hz (n=7; p=0.03) by HA (10% CO2) in chemosensitive cNTS neurons. Neither 10% nor 15% CO2 had an effect on the amplitude of sEPSCs (10–15 pA). In the presence of tetrodotoxin, HA (15% CO2) resulted in an increase in the frequency of miniature excitatory postsynaptic currents (mEPSC) from 0.4 to 0.6 Hz (n=4; p=0.006) but did not affect mEPSC amplitude (19 pA). In contrast, HA (15% CO2) resulted in a significant decrease in the frequency of spontaneous inhibitory postsynaptic currents (sIPSC) from 0.12 to 0.04 Hz (p=0.03; n=5), with no change in amplitude (6–8 pA). In nonchemosensitive cNTS neurons, HA (10% CO2) had no effect on sEPSC frequency (2.2 Hz) or amplitude (10 pA). The GABA‐A receptor agonist muscimol (3 μM) completely inhibited the firing rate of chemosensitive neurons in slices from neonatal rats aged P1‐P3, suggesting that GABA is inhibitory from birth in cNTS neurons. In conclusion, HA enhances presynaptic release of glutamate while reducing GABA release showing that the chemosensitive response of cNTS neurons is modulated by changes in synaptic input. Supported by WSU Foundation Grant.