PET Imaging of Perceptual Learning-Induced Changes in the Aged Rodent Cholinergic System

Abstract

The cholinergic system enhances attention and gates plasticity, making it a major regulator of adult learning. With aging, however, progressive degeneration of the cholinergic system impairs both the acquisition of new skills and functional recovery following neurological injury. Although cognitive training and perceptual learning have been shown to enhance auditory cortical processing, their specific impact on the cholinergic system remains unknown. Here we used [ 18 F]FEOBV, a positron emission tomography (PET) radioligand that selectively binds to the vesicular acetylcholine transporter (VAChT), as a proxy to assess whether training on a perceptual task results in increased cholinergic neurotransmission. We show for the first time that perceptual learning is associated with region-specific changes in cholinergic neurotransmission, as detected by [ 18 F]FEOBV PET imaging and corroborated with immunohistochemistry.

No Dopamine Agonist Modulation of Brain [18F]FEOBV Binding in Parkinson’s Disease

“…Similar results were obtained with ex vivo measurements of choline acetyltransferase expression, suggesting that increased regional [ 18 F]FEOBV binding accompanied increased cholinergic neurotransmission. 38 Increased regional [ 18 F]FEOBV binding is described in human subjects with isolated/idiopathic REM sleep behavior disorder and early PD. 39,40 These results may reflect increased cholinergic neurotransmission in some brain regions during the PD prodrome and early stages of PD, perhaps as part of compensatory efforts consequent to failing nigrostriatal signaling.…”

Development and preclinical evaluation of [18F]FBVM as a new potent PET tracer for vesicular acetylcholine transporter

“…To date, (−)-[ 18 F]FEOBV is the best characterized PET tracer useful for VAChT imaging in animal models [21,[49][50][51][52][53] and humans, in physiological [54] and more recently pathological [55][56][57][58][59][60][61] conditions. Therefore, we compared our new FBVM compounds to this reference tracer in the rat model by performing ex vivo biodistribution experiments and in vivo PET imaging.…”