Chlorotoxin-mediated disinhibition of noradrenergic locus coeruleus neurons using a conditional transgenic approach

Brain Research
J Michael SalbaumG Tononi

Abstract

The noradrenergic locus coeruleus (LC) has been implicated in the promotion of arousal, in focused attention and learning, and in the regulation of the sleep/waking cycle. The complex biological functions of the central noradrenergic system have been investigated largely through electrophysiological recordings and neurotoxic lesions of LC neurons. Activation of LC neurons through electrical or chemical stimulation has also led to important insights, although these techniques have limited cellular specificity and short-term effects. Here, we describe a novel method aimed at stimulating the central noradrenergic system in a highly selective manner for prolonged periods of time. This was achieved through the conditional expression of a transgene for chlorotoxin (Cltx) in the LC of adult mice. Chlorotoxin is a component of scorpion venom that partially blocks small conductance chloride channels. In this manner, the influence of GABAergic and glycinergic inhibitory inputs on LC cells is greatly reduced, while their ability to respond to excitatory inputs is unaffected. We demonstrate that the unilateral induction of Cltx expression in the LC is associated with a concomitant ipsilateral increase in the expression of markers of noradr...Continue Reading

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Citations

Jul 20, 2012·Physiological Reviews·Ritchie E BrownRobert W McCarley
Oct 16, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Patrick W HoworthAnthony E Pickering
Jan 6, 2005·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Chiara Cirelli

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