Anesthesia with dexmedetomidine and low dose isoflurane increases solute transport via the glymphatic pathway in rat brain when compared to high dose isoflurane. The glymphatic pathway transports cerebrospinal fluid through the brain, thereby facilitating waste removal. A unique aspect of this pathway is that its function depends on the state of consciousness of the brain and is associated with norepinephrine activity. A current view is that all anesthetics will increase glymphatic transport by inducing unconsciousness. This view implies that the effect of anesthetics on glymphatic transport should be independent of their mechanism of action, as long as they induce unconsciousness. We tested this hypothesis by comparing the supplementary effect of dexmedetomidine, which lowers norepinephrine, with isoflurane only, which does not. Female rats were anesthetized with either isoflurane (N = 8) or dexmedetomidine plus low-dose isoflurane (N = 8). Physiologic parameters were recorded continuously. Glymphatic transport was quantified by contrast-enhanced magnetic resonance imaging. Cerebrospinal fluid and gray and white matter volumes were quantified from T1 maps, and blood vessel diameters were extracted from time-of-flight magnetic resonance angiograms. Electroencephalograms were recorded in separate groups of rats. Glymphatic transport was enhanced by 32% in rats anesthetized with dexmedetomidine plus low-dose isoflurane when compared with isoflurane. In the hippocampus, glymphatic clearance was sixfold more efficient during dexmedetomidine plus low-dose isoflurane anesthesia when compared with isoflurane. The respiratory and blood gas status was comparable in rats anesthetized with the two different anesthesia regimens. In the dexmedetomidine plus low-dose isoflurane rats, spindle oscillations (9 to 15 Hz) could be observed but not in isoflurane anesthetized rats. We propose that anesthetics affect the glymphatic pathway transport not simply by inducing unconsciousness but also by additional mechanisms, one of which is the repression of norepinephrine release. Delta rhythm orchestrates the neural activity underlying the resting state BOLD signal via phase-amplitude coupling. Spontaneous ongoing neuronal activity is a prominent feature of the mammalian brain. Temporal and spatial patterns of such ongoing activity have been exploited to examine large-scale brain network organization and function. However, the neurophysiological basis of this spontaneous brain activity as detected by resting-state functional Magnetic Resonance Imaging (fMRI) remains poorly understood. To this end, multi-site local field potentials (LFP) and blood oxygenation level-dependent (BOLD) fMRI were simultaneously recorded in the rat striatum along with local pharmacological manipulation of striatal activity. Results demonstrate that delta () band LFP power negatively, while beta () and gamma () band LFPs positively correlated with BOLD fluctuation. Furthermore, there was strong cross-frequency phase-amplitude coupling (PAC), with the phase of LFPs significantly modulating the amplitude of the high frequency signal. Enhancing dopaminergic neuronal activity significantly reduced ventral striatal functional connectivity, LFP-BOLD correlation, and the PAC effect. These data suggest that different frequency bands of the LFP contribute distinctively to BOLD spontaneous fluctuation and that PAC is the organizing mechanism through which low frequency LFPs orchestrate neural activity that underlies resting state functional connectivity.

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6
Fiscal Year
2018
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National Institute on Drug Abuse
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Liu, Dong; Lu, Hanbing; Stein, Elliot et al. (2018) Brain regional synchronous activity predicts tauopathy in 3×TgAD mice. Neurobiol Aging 70:160-169
Benveniste, Helene; Lee, Hedok; Ding, Fengfei et al. (2017) Anesthesia with Dexmedetomidine and Low-dose Isoflurane Increases Solute Transport via the Glymphatic Pathway in Rat Brain When Compared with High-dose Isoflurane. Anesthesiology 127:976-988
Brynildsen, Julia K; Hsu, Li-Ming; Ross, Thomas J et al. (2017) Physiological characterization of a robust survival rodent fMRI method. Magn Reson Imaging 35:54-60
Jaime, Saul; Gu, Hong; Sadacca, Brian F et al. (2017) Delta Rhythm Orchestrates the Neural Activity Underlying the Resting State BOLD Signal via Phase-amplitude Coupling. Cereb Cortex :1-15
Ash, Jessica A; Lu, Hanbing; Taxier, Lisa R et al. (2016) Functional connectivity with the retrosplenial cortex predicts cognitive aging in rats. Proc Natl Acad Sci U S A 113:12286-12291
Belcher, Annabelle M; Yen, Cecil Chern-Chyi; Notardonato, Lucia et al. (2016) Functional Connectivity Hubs and Networks in the Awake Marmoset Brain. Front Integr Neurosci 10:9
Hsu, Li-Ming; Liang, Xia; Gu, Hong et al. (2016) Constituents and functional implications of the rat default mode network. Proc Natl Acad Sci U S A 113:E4541-7
Brynildsen, Julia K; Najar, Julie; Hsu, Li-Ming et al. (2016) A novel method to induce nicotine dependence by intermittent drug delivery using osmotic minipumps. Pharmacol Biochem Behav 142:79-84
Vaupel, D B; Schindler, C W; Chefer, S et al. (2016) Delayed emergence of methamphetamine's enhanced cardiovascular effects in nonhuman primates during protracted methamphetamine abstinence. Drug Alcohol Depend 159:181-9
Le Foll, Bernard; Chefer, Svetlana I; Kimes, Alane S et al. (2016) Impact of short access nicotine self-administration on expression of ?4?2* nicotinic acetylcholine receptors in non-human primates. Psychopharmacology (Berl) 233:1829-35

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