Medullary Norepinephrine Neurons Modulate Local Oxygen Concentrations in the Bed Nucleus of the Stria Terminalis

Abstract

Neurovascular coupling is understood to be the underlying mechanism of functional hyperemia, but the actions of the neurotransmitters involved are not well characterized. Here we investigate the local role of the neurotransmitter norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat by measuring O₂, which is delivered during functional hyperemia. Extracellular changes in norepinephrine and O₂ were simultaneously monitored using fast-scan cyclic voltammetry. Introduction of norepinephrine by electrical stimulation of the ventral noradrenergic bundle or by iontophoretic ejection induced an initial increase in O₂ levels followed by a brief dip below baseline. Supporting the role of a hyperemic response, the O₂ increases were absent in a brain slice containing the vBNST. Administration of selective pharmacological agents demonstrated that both phases of this response involve β-adrenoceptor activation, where the delayed decrease in O₂ is sensitive to both α- and β-receptor subtypes. Selective lesioning of the locus coeruleus with the neurotoxin DSP-4 confirmed that these responses are caused by the noradrenergic cells originating in the nucleus of the solitary tract and A1 cell groups. Overall, these results support that non-coerulean norepinephrine release can mediate activity-induced O₂ influx in a deep brain region.

Stress and Drug Dependence Differentially Modulate Norepinephrine Signaling in Animals with Varied HPA Axis Function

“…Although blockade of a 2C receptors did not increase norepinephrine overflow, a 2C inhibition generated a large alkaline flux following stimulated norepinephrine release, seen in Figure 1f as blue current just below norepinephrine peak oxidation potential. The a 2C receptors in the vBNST may therefore be positioned to regulate blood flow/ metabolism in the vBNST (Bucher et al, 2014).…”

Electrochemical carbon fiber-based technique for simultaneous recordings of brain tissue PO2, pH, and extracellular field potentials

“…The sub-second time resolution of FCV allows detection of events that occur at the onset of neuronal activity and precede increases in blood flow (Logothetis et al 2001). Separate electrochemical detection of tissue partial pressure of oxygen (PtO 2 ) and pH using FCV has been achieved previously (Bucher et al 2014; Hosford et al 2017; Takmakov et al 2010). Here we describe a novel FCV-based technique that enables simultaneous recordings of key variables representing the metabolic state of the brain: brain tissue PO 2 , pH and neuronal activity.…”

Correlation of transient adenosine release and oxygen changes in the caudate‐putamen

“…; Bucher et al . ). To measure adenosine and oxygen levels, the FSCV waveform can be modified to scan up to 1.5 V and down to −1.4 V to both oxidize adenosine and reduce oxygen (Cechova and Venton ).…”