Effects of the α₂‐adrenergic receptor agonist dexmedetomidine on neural, vascular and BOLD fMRI responses in the somatosensory cortex

Abstract

This paper describes the effects of dexmedetomidine (DEX) 5 the active ingredient of medetomidine which is the latest popular sedative for functional magnetic resonance imaging (fMRI) in rodents 5 on multiple unit activity, local field potential (LFP), cerebral blood flow (CBF), pial vessel diameter (indicative of cerebral blood volume; CBV), and blood-oxygenation-level-dependent (BOLD) fMRI. These measurements were obtained from the rat somatosensory cortex during 10-s forepaw stimulation. We found that the continuous intravascular systemic infusion of DEX (50μg/kg/h, doses typically used in fMRI studies) caused epileptic activities and that supplemental isoflurane administration of ~0.3% helped suppress the development of epileptic activities and maintained robust neuronal and hemodynamic responses up to 3 hours. Supplemental administration of nitrous oxide (N2O) in addition to DEX nearly abolished hemodynamic responses even if neuronal activity remained. Under DEX-ISO anesthesia, spike firing rate and the delta power of LFP increased, while beta and gamma power decreased compared to ISO-only anesthesia. DEX administration caused pial arteries and veins to constrict nearly equally, resulting in decreases in baseline CBF and CBV. Evoked LFP and CBF responses to forepaw stimulation were largest at a frequency of 8–10 Hz, and a non-linear relationship was observed. Similarly, BOLD fMRI responses measured at 9.4 Tesla were largest at a frequency of 10 Hz. Both pial arteries and veins dilated rapidly (artery, 32.2%; vein, 5.8%), while venous diameter changes returned to baseline slower than arteries. These results will be useful for designing, conducting and interpreting fMRI experiments under DEX sedation.

Hemodynamic-based Mapping of Neural Activity in Medetomidine-sedated Rats using a 1.5T Compact Magnetic Resonance Imaging System: A Preliminary Study

“…Although this optimal frequency differed considerably from that of ¡-chloralose (3 Hz), 2 it agreed with that of dexmedetomidine, 10 a medetomidine isomer, and was similar to that of isoflurane (12 Hz) and its isomer enflurane (10 Hz) as described by Masamoto and Kanno 2 and references therein. From this, we infer that the differences in the pharmacological properties of agents used in anesthesia and sedation serve important roles in their respective different optimal frequencies.…”

Neural and Hemodynamic Responses to Optogenetic and Sensory Stimulation in the Rat Somatosensory Cortex

“…The choice of S1FL is owing to prior extensive studies of neurovascular coupling in the somatosensory cortex using optical [14][15][16][17][18] and fMRI approaches. [19][20][21][22][23][24] We compared dynamic BOLD response functions, and the relationship between neural activities and hemodynamic responses induced by optical and sensory stimulation. Further, the neurovascular relationships were examined by decoupling the presynaptic firing rate from the postsynaptic processing with application of antagonists to ionotropic GluRs.…”

Functional network study on the wild type and DISC1 transgenic mice

“…Although increasingly used in rodent studies, medetomidine induces negative effects on cardiovascular functions and causes dose-dependent vasoconstriction (Sinclair, 2003;Jonckers et al, 2015). In addition, animals under medetomidine anaesthesia were reported to show epileptic activities (Fukuda et al, 2013;Grandjean et al, 2014b). Fukuda et al (2013) proposed a combination of low-dose isoflurane and dexmedetomidine to suppress potential epileptic activity without sacrificing the desired effects of medetomidine.…”

“…In addition, animals under medetomidine anaesthesia were reported to show epileptic activities (Fukuda et al, 2013;Grandjean et al, 2014b). Fukuda et al (2013) proposed a combination of low-dose isoflurane and dexmedetomidine to suppress potential epileptic activity without sacrificing the desired effects of medetomidine. In addition, the vasodilatory effect of isoflurane and the vasoconstrictive effect of medetomidine appeared to compromise each other (Fukuda et al, 2013), showing promising effects of the combination regimen for rodent fMRI experiments.…”

“…Fukuda et al (2013) proposed a combination of low-dose isoflurane and dexmedetomidine to suppress potential epileptic activity without sacrificing the desired effects of medetomidine. In addition, the vasodilatory effect of isoflurane and the vasoconstrictive effect of medetomidine appeared to compromise each other (Fukuda et al, 2013), showing promising effects of the combination regimen for rodent fMRI experiments. This study compared changes in regional connectivity in mice using rsfMRI under six anaesthesia regimens relevant to rodent functional imaging studies:…”