Our research interest is on the study of the activity and connection of medullary parasympathetic and pre-sympathetic cardiovascular neurons in rats. Cardiac vagal neurons (CVNs) in the medulla play a critical role in the control of heart rate and cardiac function. The activity of CVNs is diminished and unresponsive in many diseases. We showed that spontaneous inhibitory postsynaptic current (sIPSC) activity could be recorded in CVNs in nucleus ambiguus (NA), and it was mediated by GABAA and glycine receptors. Our data also suggest that there is a tonic inhibitory current (Itonic) mediated by extrasynaptic GABAA receptors in CVNs. Pentobarbital can directly activate GABAA receptors located at synaptic and extrasynaptic sites in CVNs and the increased phasic or tonic GABAA receptor conductance silences CVNs and inhibits cardiovascular function.
Many studies have reported that exposure to highly selective serotonin reuptake inhibitors (SSRIs), citalopram, during perinatal stage in rats produced profound changes in the serotonergic system. Such neurochemical alterations persisted into adulthood. We further utilize such strategy to investigate whether the effects of serotonergic abnormalities in medulla play a role on the autonomic function in SSRI-treated rats. Our SSRI-treated animals showed an imbalanced autonomic function. We further investigate the effects of serotonergic abnormality on other brain functions. We found that there are reduced GABAB receptor activity and tonic inhibition on noradrenergic neurons in the locus coeruleus (LC), which might result in the significantly higher spontaneous activity of LC neurons seen in these male, but not female, SSRI-treated animals.
We also investigated the role of GABAB receptors in mediating ERK1-dependent autoregulation of the stability of GABABR-activated whole-cell current, in addition to its well-known effect on gated potassium channels, to cause a tonic current in LC neurons.