title: Pharmacological insight into neurotransmission origins of resting-state functional connectivity: α2-adrenergic agonist vs antagonist.
abstract: Resting-state functional connectivity MRI has emerged as a powerful tool for mapping large-scale neural networks based on synchronous BOLD signal; however, the neurobiological mechanisms are still unknown. To understand its neural substrates, especially the underlying neurotransmission, we applied pharmacological modulation with a receptor specific agonist and antagonist. Resting and evoked electrophysiology and BOLD signals in rat brains were measured under infusion of α2-adrenergic receptor agonist, medetomidine, the antagonist, atipamezole, and the vehicle individually. Both somatosensory BOLD activation and evoked potential were increased significantly under medetomidine compared to the vehicle while atipamezole slightly decreased both. The interhemispheric correlation at the resting state, in contrast, was suppressed by medetomidine but increased by atipamezole in regions with high receptor densities including the somatosensory cortex and thalamus. No change was seen in the caudate putamen, where receptor occupancy is low. The regional difference in connectivity was not related to cerebral blood flow, indicating that BOLD signal correlation is unlikely due to the vascular effects of the drugs. Resting intracortical recording exhibited agonist/antagonist dependent changes in beta and gamma bands that correlated with the BOLD functional connectivity measure. Our results confirm an important role of the adrenergic system on functional connectivity and suggest a neurotransmission basis of the phenomenon.
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Fatima A
authors.initials: FA
authors.lastname: Nasrallah
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Si-Min Amanda
authors.initials: SA
authors.lastname: Low
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Si Kang
authors.initials: SK
authors.lastname: Lew
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore.
authors.forename: Kaina
authors.initials: K
authors.lastname: Chen
authors.affiliation: Magnetic Resonance Imaging Group, Singapore Bioimaging Consortium, Agency for Science Technology and Research, Singapore; Clinical Imaging Research Centre, National University of Singapore, Singapore; Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: Chuang_Kai_Hsiang@sbic.a-star.edu.sg.
authors.forename: Kai-Hsiang
authors.initials: KH
authors.lastname: Chuang
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001931:Brain Mapping; D002560:Cerebrovascular Circulation / Q000187:drug effects; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D007091:Image Processing, Computer-Assisted; D007093:Imidazoles / Q000494:pharmacology; D008279:Magnetic Resonance Imaging; D008297:Male; D020926:Medetomidine / Q000494:pharmacology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*; D012146:Rest; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D007093:Imidazoles; D018341:Receptors, Adrenergic, alpha-2; C050701:atipamezole; D020926:Medetomidine
keywords: Adrenergic; Functional MRI; Functional connectivity; Neural basis; Resting state