Spatiotemporal dynamics of noradrenaline during learned behaviour

Mriganka Sur

Abstract:

Noradrenaline released from the locus coeruleus (LC) is a ubiquitous
neuromodulator that has been linked to multiple functions including arousal,
action and sensory gain, and learning. Whether and how activation of
noradrenaline-expressing neurons in the LC (LC-NA) facilitates different components
of specific behaviours is unknown. Here we show that LC-NA activity displays distinct
spatiotemporal dynamics to enable two functions during learned behaviour:
facilitating task execution and encoding reinforcement to improve performance
accuracy. To examine these functions, we used a behavioural task in mice with graded
auditory stimulus detection and task performance. Optogenetic inactivation of the
LC demonstrated that LC-NA activity was causal for both task execution and
optimization. Targeted recordings of LC-NA neurons using photo-tagging,
two-photon micro-endoscopy and two-photon output monitoring showed that
transient LC-NA activation preceded behavioural execution and followed
reinforcement. These two components of phasic activity were heterogeneously
represented in LC-NA cortical outputs, such that the behavioural response signal was
higher in the motor cortex and facilitated task execution, whereas the negative
reinforcement signal was widely distributed among cortical regions and improved
response sensitivity on the subsequent trial. Modular targeting of LC outputs thus
enables diverse functions, whereby some noradrenaline signals are segregated
among targets, whereas others are broadly distributed.