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

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.

Redefining Noradrenergic Neuromodulation of Behavior: Impacts of a Modular Locus Coeruleus Architecture

“…These methods have recently been applied to the LC to test the hypothesis that function-specific neuromodulation is achieved by subpopulations of LC neurons with unique anatomical connectivity in the brain. One approach has been to use the synthetic noradrenergic-neuronspecific promoter, PRS, to selectively express activity-modifying transgenes in LC neurons Lonergan et al, 2005;Howorth et al, 2009a,b;Hickey et al, 2014;Li et al, 2016;Hirschberg et al, 2017;Vazey et al, 2018;Cope et al, 2019;Xiang et al, 2019). Studies using PRS-containing canine adenoviral vectors (CAVs) (Junyent and Kremer, 2015) have been particularly helpful for dissecting the role of specific LC projections by enabling selective optogenetic or chemogenetic activation ( Fig.…”

Anticipatory energization revealed by pupil and brain activity guides human effort-based decision making

“…NA activity can directly influence pupil size and is tightly linked to changes in pupil dilation (Joshi et al 2016; Reimer et al 2016; Gelbard-Sagiv et al 2018), making phasic, task-related pupil an accurate indicator of brain arousal states (Yüzgeç et al 2018; McGinley et al 2015). However, it remains unclear whether the effort signals that guide choices would also draw on the same pupil-linked NA arousal system that has been found to facilitate actual behavior energization (Varazzani et al 2015; Zénon, Sidibé, and Olivier 2014; Borderies et al 2020; Xiang et al 2019).…”

Precise and pervasive phasic bursting in locus coeruleus during maternal behavior

“…We found that LC activity consistently preceded the change in speed associated with initiating retrieval by several hundred ms. LC fluorescence was highly correlated with speed during retrieval periods, yet these two measures were either not or negatively correlated during pup approach. Several recent studies reported significant correlations between phasic activation of LC and motion on approach to a learned reward location 47,48 . One interpretation of our results that is concordant with these previous findings is that an important feature of LC's regulation of maternal behavior is the promotion of actions that achieve the motivational goal of delivering the pup to a specific reward-associated location (the nest).…”