Glutamatergic Activity in the Nucleus of the Solitary Tract contributes to the Circadian Regulation of Blood Pressure
Authors: Crowthers Raymond , Greenwald Eric , Martinez Diana 
Published: May 2022

Cardiorespiratory parameters including blood pressure are governed by a 24‐hour circadian rhythm. Blood pressure follows a circadian cycle and dips during the resting/sleeping period while peaking during the active/awake period. During sleep blood pressure is 10%‐20% lower than average daytime blood pressure, a phenomenon described as “dipping”. The brain regions and mechanisms by which the circadian rhythm of blood pressure is controlled are not fully understood. To address this knowledge gap, we examined the nucleus of the solitary tract (nTS). The nTS is the first central site for integration and modulation of reflexes including the baroreflex. The nTS receives sensory information through glutamate release from baroreceptors that sense changes in blood pressure, eliciting reflex responses in the nTS to maintain BP homeostasis. Previous studies have shown that injections of glutamate or increases of extracellular glutamate decrease blood pressure. Due to its integral role in the autonomic system, we hypothesized that the nTS is involved in circadian blood pressure regulation through alterations in glutamate. Specifically, the present study sought to identify if decreased glutamate raised blood pressure during the active period and if increased glutamate reduced blood pressure in the inactive period. To address this, we used 7‐week‐old male Sprague Dawley rats and a combination of electrophysiology, molecular methods, immunohistochemistry, and 24/7 telemetry. Rats acclimated for 2 weeks prior to telemetry recordings. Measurements were compared at four different time points in one day (6 hours apart) except for electrophysiological recordings which were taken 12 hours apart. During the active period, blood pressure significantly increased in comparison to the inactive period. We next examined the relationship between changes in blood pressure and changes in glutamatergic activity. We first determined if activation of glutamatergic neurons differed across the 4 time periods. We took 30 µm of coronal slices containing the nTS (at the level of area postrema) from perfused animals. Active glutamatergic neurons (denoted by cFos expression) significantly decreased during the active period in comparison to the inactive period. To examine if this increase in glutamatergic neuronal cFos expression correlated with channel expression, we used western blot and found that the expression of AMPA receptors (GluA1 subunit) also decreased during the active period. During the active period, the resting membrane potential of nTS neurons were hyperpolarized in comparison to the inactive period. This lead to a significant decrease in spontaneous excitatory post‐synaptic currents in nTS neurons during the active period. The data indicate that glutamatergic activity decreased during the active period when blood pressure was higher in comparison to the inactive period. Taken together, these results suggest that nTS glutamatergic activity may have a circadian pattern and may contribute to the circadian blood pressure rhythm.