Activation of spinal membrane ERs with intrathecal E2-BSA restores pLTF in OVX rats. A, B, Representative traces of integrated phrenic neurograms over 90 min during and following aIH in OVX female rats receiving intrathecal (A) E2-BSA (n = 5) to activate membrane E2 receptors or (B) control BSA alone (n = 5). Baseline is indicated by the dashed line. E2-BSA given 15 min before aIH resulted in a progressive increase in phrenic nerve burst amplitude above baseline (dashed line). Rats receiving BSA alone did not express pLTF. C, In the absence of aIH, time-control (TC) rats (n = 6) receiving intrathecal injections displayed no time-dependent changes in phrenic nerve burst amplitudes over the same 90 min period. D, Quantification of pLTF magnitude following pretreatment with intrathecal E2-BSA or BSA alone reflect an E2-BSA-induced enhancement of phrenic burst amplitude 60 min following aIH relative to baseline, BSA-treated control rats, and time controls. The 50 nm E2-BSA dose was derived from dose–response studies (inset). E, F, Intrathecal E2-BSA led to enhanced phrenic amplitude in response to hypoxia (E), but had minimal impact on phrenic burst frequency (F).