Behavioral correlates of activity of optogenetically identified locus coeruleus noradrenergic neurons in rats performing T-maze tasks

Liyang Xiang,Susan J Sara,Hongying Gao,Antoine Harel,Anthony E Pickering,Sidney I Wiener

doi:10.1038/s41598-018-37227-w

Abstract

The nucleusLocus Coeruleus (LC) is the major source of forebrain norepinephrine. LC is implicated in arousal, response to novelty, and cognitive functions, including decision-making and behavioral flexibility. One hypothesis is that LC activation promotes rapid shifts in cortical attentional networks following changes in environmental contingencies. Recent recordings further suggest LC is critical for mobilizing resources to deal with challenging situations. In the present study optogenetically identified LC neuronal activity was recorded in rats in a self-paced T-maze. Rats were trained on visual discrimination; then place-reward contingencies were instated. In the session where the animal shifted tasks the first time, the LC firing rate after visual cue onset increased significantly, even as the animal adhered to the previous rule. Firing rate also increased prior to crossing photodetectors that controlled stimulus onset and offset, and this was positively correlated with accelerations, consistent with a role in mobilizing effort. The results contribute to the growing evidence that the noradrenergic LC is essential for behavioral adaptation by promoting cognitive flexibility and mobilizing effort in face of changing environmental contingencies.

Highlights

The importance of the noradrenergic nucleus Locus Coeruleus (LC) in cognitive processes is well-acknowledged, yet little understood
Within trials, the response latency was much shorter in LC than in PFC10, indicating that the LC response was not mediated through the prefrontal cortex (PFC), as had been hypothesized
This study is the first to document the responses of optogenetically identified noradrenergic LC neurons during unrestrained locomotion, permitting behavioral correlates of these identified units, including locomotor acceleration, to be observed

Summary

Introduction

The importance of the noradrenergic nucleus Locus Coeruleus (LC) in cognitive processes is well-acknowledged, yet little understood. Recordings from the LC in rats supported a role in vigilance[6] These neurons respond with a phasic burst to novel sensory stimuli of all modalities, but habituate rapidly[7] unless the stimulus predicts a reward[8]. Within trials, the response latency was much shorter in LC than in PFC10, indicating that the LC response was not mediated through the PFC, as had been hypothesized These results, and others from pharmacological studies suggesting that NE facilitates performance in reversal and extra-dimensional shift tasks[11,12], led to a theory of function of the LC-NE system termed ‘network reset’[13]. Overall the results support the notion that the noradrenergic system is critical for mobilizing resources and preparing the appropriate response to face challenging situations[4,16]

Methods

Results

Conclusion