Two types of locus coeruleus norepinephrine neurons drive reinforcement learning

Abstract

The cerebral cortex generates flexible behavior by learning. Reinforcement learning is thought to be driven by error signals in midbrain dopamine neurons. However, they project more densely to basal ganglia than cortex, leaving open the possibility of another source of learning signals for cortex. The locus coeruleus (LC) contains most of the brain's norepinephrine (NE) neurons and project broadly to cortex. We measured activity from identified mouse LC-NE neurons during a behavioral task requiring ongoing learning from reward prediction errors (RPEs). We found two types of LC-NE neurons: neurons with wide action potentials (type I) were excited by positive RPE and showed an increasing relationship with change of choice likelihood. Neurons with thin action potentials (type II) were excited by lack of reward and showed a decreasing relationship with change of choice likelihood. Silencing LC-NE neurons changed future choices, as predicted from the electrophysiological recordings and a model of how RPEs are used to guide learning. We reveal functional heterogeneity of a neuromodulatory system in the brain and show that NE inputs to cortex act as a quantitative learning signal for flexible behavior.

Cellular and Circuit Organization of the Locus Coeruleus of Adult Mice

“…However, "narrow" units are heavily biased toward the ventral part of the LC (Su & Cohen, 2022; N. K. Totah et al, 2018), while FFs as we described here may be dorsally biased (Loughlin et al, 1986). In addition, FFs do not exhibit a higher spontaneous firing rate than MPs (Fig.…”

“…Establishing a real correspondence between cell types as we discovered here and single unit types is important for the field, warranting a new systematic study (Su & Cohen, 2022; N. K. Totah et al, 2018; N. K. B. Totah et al, 2019).…”

“…Nevertheless, it is unknown how well in vitro intracellular waveforms correlate with in vivo extracellular ones and thus we cannot rule out the possibility that FF cells correspond to those "narrow" units. Establishing a real correspondence between cell types as we discovered here and single unit types is important for the field, warranting a new systematic study (Su & Cohen, 2022;N. K. Totah et al, 2018;N.…”

“…Furthermore, FFs could sustain higher frequency firing than MPs with large suprathreshold depolarizing current injections. The fact that FFs fire narrower spikes than MPs suggests FF may correspond to “narrow” units identified during extracellular recordings of LC neurons, while MP may correspond to those “wide” units (Su & Cohen, 2022; N. K. Totah, Neves, Panzeri, Logothetis, & Eschenko, 2018). However, “narrow” units are heavily biased toward the ventral part of the LC (Su & Cohen, 2022; N. K. Totah et al, 2018), while FFs as we described here may be dorsally biased (Loughlin et al, 1986).…”

“…Furthermore, FFs could sustain higher frequency firing than MPs with large suprathreshold depolarizing current injections. The observation that FFs fire narrower spikes than MPs suggests FF may correspond to "narrow" units identified during extracellular recordings of LC neurons, while MP may correspond to those "wide" units (Su & Cohen, 2022; N. K. Totah, Neves, Panzeri, Logothetis, & Eschenko, 2018). However, "narrow" units are heavily biased toward the ventral part of the LC (Su & Cohen, 2022;N.…”