RT Journal Article SR Electronic T1 Reward devaluation attenuates cue-evoked sucrose seeking and is associated with the elimination of excitability differences between ensemble and non-ensemble neurons in the nucleus accumbens JF eneuro JO eNeuro FD Society for Neuroscience SP ENEURO.0338-19.2019 DO 10.1523/ENEURO.0338-19.2019 A1 Meike C. Sieburg A1 Joseph J. Ziminski A1 Gabriella Margetts-Smith A1 Hayley Reeve A1 Leonie S. Brebner A1 Hans S. Crombag A1 Eisuke Koya YR 2019 UL http://www.eneuro.org/content/early/2019/11/07/ENEURO.0338-19.2019.abstract AB Animals must learn relationships between foods and the environmental cues that predict their availability for survival. Such cue-food associations are encoded in sparse sets of neurons or ‘neuronal ensembles’ in the nucleus accumbens (NAc). For these ensemble-encoded, cue-controlled appetitive responses to remain adaptive, they must allow for their dynamic updating depending on acute changes in internal states such as physiological hunger or the perceived desirability of food. However, how these neuronal ensembles are recruited and physiologically modified following the update of such learned associations is unclear. To investigate this, we examined the effects of devaluation on ensemble plasticity at the levels of recruitment, intrinsic excitability, and synaptic physiology in sucrose conditioned Fos-GFP mice that express green fluorescent protein (GFP) in recently activated neurons. Neuronal ensemble activation patterns and their physiology were examined using immunohistochemistry and slice electrophysiology, respectively. Reward-specific devaluation following four days of ad lib sucrose consumption, but not general caloric devaluation, attenuated cue-evoked sucrose seeking. This suggests that changes in the hedonic and/or incentive value of sucrose, and not caloric need drove this behavior. Moreover, devaluation attenuated the size of the neuronal ensemble recruited by the cue in the NAc shell. Finally, it eliminated the relative enhanced excitability of ensemble (GFP+) neurons against non-ensemble (GFP–) neurons observed under Non-devalued conditions, and did not induce any ensemble-specific changes in excitatory synaptic physiology. Our findings provide new insights into neuronal ensemble mechanisms that underlie the changes in the incentive and/or hedonic impact of cues that support adaptive food seeking.Significance statement Learned associations between food and the cues that predict their availability are encoded in neuronal ensembles in reward-relevant brain areas, such as the nucleus accumbens. Such learning is often accompanied by synaptic and intrinsic plasticity within these ensemble neurons. However, it is unclear how these plasticity changes manifest specifically in cue-activated neurons in response to decreases in reward value, e.g. following reward-specific or general (caloric) devaluation. We reveal that shifts in excitability, but not excitatory synaptic physiology between ensemble and non-ensemble neurons in the nucleus accumbens shell coincide with reward-specific devaluation. Our findings provide new insights into how changes in the perceived properties of food reward update cue-food associations by potentially fine-tuning neuronal excitability.