5HT1A receptors inhibit glutamate inputs to cardiac vagal neurons post-hypoxia/hypercapnia.

Synaptic inputs to cardiac vagal neurons (CVNs) regulate parasympathetic activity to the heart. Previous work has shown insults such as hypoxia and hypercapnia (H/H) alter CVN activity by activating post-synaptic serotonergic, purinergic, and glutamatergic receptors in CVNs. This study examines the role of serotonergic 5HT1A receptors in modulating these excitatory neurotransmissions to CVNs during control conditions, H/H and recovery from H/H. Excitatory post-synaptic currents (EPSCs) were recorded from identified CVNs in vitro before, during and post H/H. The 5HT1A receptor antagonist WAY 100635 had no effect on EPSCs in CVNs before, and during H/H. However, during recovery from H/H inspiratory-related excitatory serotonergic and purinergic pathways were recruited to excite CVNs. However, when these serotonergic and purinergic pathways are blocked, the 5HT1A receptor antagonist WAY 100635 restores an excitatory glutamatergic neurotransmission to CVNs. This study indicates endogenous activation of serotonergic 5HT1A receptors diminishes glutamatergic neurotransmission to CVNs following H/H, likely via a presynaptic site of action.