Phasic dopamine reinforces distinct striatal stimulus encoding in the olfactory tubercle driving dopaminergic reward prediction

Abstract

The learning of stimulus-outcome associations allows for predictions about the environment. Ventral striatum and dopaminergic midbrain neurons form a larger network for generating reward prediction signals from sensory cues. Yet, the network plasticity mechanisms to generate predictive signals in these distributed circuits have not been entirely clarified. Also, direct evidence of the underlying interregional assembly formation and information transfer is still missing. Here we show that phasic dopamine is sufficient to reinforce the distinctness of stimulus representations in the ventral striatum even in the absence of reward. Upon such reinforcement, striatal stimulus encoding gives rise to interregional assemblies that drive dopaminergic neurons during stimulus-outcome learning. These assemblies dynamically encode the predicted reward value of conditioned stimuli. Together, our data reveal that ventral striatal and midbrain reward networks form a reinforcing loop to generate reward prediction coding.

Hierarchical cross-scale analysis identifies parallel ventral striatal networks coding for dynamic and stabilized olfactory reward predictions

“…S6A ). Considering that the CS-bound value coding units are reinforced from pre-existing odor-specific responses (Oettl et al, 2020), we wondered whether the single-units not encoding monotonic RP still contributed collectively to it. Indeed, upon removal of all units with monotonic RP coding in the transient-cluster, the cumulative firing rate of the remaining units still reflected a robust population coding of the monotonic RP ( Fig.…”

“…Recent studies have revealed that Tu neurons are recruited by stimuli that predict rewards upon conditioning (Gadziola et al, 2020, Millman and Murthy, 2020, Murata et al, 2015, Oettl et al, 2020, Zhang et al, 2017). In these studies, the duration of the conditioned stimulus partially overlaps with US.…”

“…The stability of the RP representation at CS may relate to its formation through synaptic plasticity (Wieland et al, 2015). In fact, the stimulus response potentiation evolves gradually upon repeated pairing of the odor with phasic dopamine in awake mice (Oettl et al, 2020). Once emerged, these RP-coding CS signals in the Tu drive downstream the equivalent RP responses of VTA DAN (Oettl et al, 2020).…”

“…We used an in-house designed tetrode array for dual-site recordings described in detail in Oettl et al, 2020. In brief, custom-designed printed circuit boards (PCB) (±10 μm, Würth Electronics) with a soldered Molex SlimStack connector served as an electrode interface board (EIB).…”

“…Here we developed a hierarchical approach, from mesoscale fMRI to cellular recordings, to dissect olfactory reward prediction coding in the context of stimulus-outcome learning. During such reinforcement learning, an initially neutral sensory stimulus (called a conditioned stimulus; CS) is paired repeatedly after a waiting interval with reward (an unconditioned stimulus; US) (Flagel et al, 2011, Oettl et al, 2020, Schultz, 2000, Setlow et al, 2003, Takahashi et al, 2016). Midbrain dopamine neurons (DAN) show firing responses to the CS and US.…”