A stable, distributed code for cue value in mouse cortex during reward learning

Abstract

The ability to associate reward-predicting stimuli with adaptive behavior is frequently attributed to the prefrontal cortex, but the stimulus-specificity, spatial distribution, and stability of pre-frontal cue-reward associations are unresolved. We trained headfixed mice on an olfactory Pavlovian conditioning task and measured the coding properties of individual neurons across space (prefrontal, olfactory, and motor cortices) and time (multiple days). Neurons encoding cues or licks were most common in olfactory and motor cortex, respectively. By quantifying the responses of cue-encoding neurons to six cues with varying probabilities of reward, we unexpectedly found value coding, including coding of trial-by-trial reward history, in all regions we sampled. We further found that prefrontal cue and lick codes were preserved across days. Our results demonstrate that individual prefrontal neurons stably encode components of cue-reward learning within a larger spatial gradient of coding properties.

Reward contingency modulates olfactory bulb output via pathway-dependent peri-somatic inhibition

“…While only a subset of pyramidal neurons from the piriform cortex project to the olfactory bulb 52 , a recent imaging study from olfactory bulb-projecting fibres showed value-like activity when the task depended on olfactory cues 53 . It is unclear why we did not observe the widespread reward-related modulation in tufted cells, even though some value-like activity is present in the anterior olfactory nucleus 4 , a region known to have modulatory influence over tufted cells 17 . Since the anterior olfactory nucleus has multiple compartments 54 with each with distinct long-range connectivity 55 , it will be crucial for future studies to resolve how these subregions contribute to associating values with olfactory stimuli.…”

“…One important source of reward-related signals to OB is the direct or indirect feedback projec,ons from olfactory cor,ces. Value-like modula,on of olfactory responses occurs in many parts of the brain: It has been observed in the prefrontal cortex 4,45 , orbitofrontal cortex 4,45 , hippocampus 46 , olfactory tubercle [47][48][49][50] , piriform cortex 4,51 , and anterior olfactory nucleus 4 , although there may be regional differences, for example, in the long-term stability of expression 45 . Of par,cular interest is the piriform cortex, which serves as a gateway for processed signals for modula,on of the mitral cells 17 .…”

“…quan,ty of expected reward [1][2][3][4][5] . This modula,on is o_en interpreted as represen,ng subjec,ve value 6,7 .…”

Basolateral amygdala population coding of a cued reward seeking state depends on orbitofrontal cortex

“…To project population activity onto the CS+ dimension (Ottenheimer et al, 2023), we normalized the unsmoothed firing rate of each neuron in a PSTH spanning baseline and CS+ activity so that each neuron's activity ranged from 0 to 1. We then calculated the difference between each neuron's CS+ evoked activity (0 to 2s) and baseline activity (-15 to 0s), producing a vector describing how modulated each neuron is to the CS+ relative to its total range of firing.…”

Neural signatures of stress susceptibility and resilience in the amygdala-hippocampal network

“…The reciprocally connected amygdala (AMY) and ventral hippocampus (vHPC) are crucial nodes in an extended network responsible for generating emotional and motivated behavior . In addition to its role in threat detection and anxiety-related behavior, the basolateral amygdala (BLA) generates outcome-specific reward representations to guide decision-making (38)(39)(40)(41)(42)(43)(44)(45). Ventral CA1 (vCA1) has also been shown to encode reward-predictive stimuli and drive rewardrelated approach behaviors (46)(47)(48)(49)(50).…”