Individual Variation in Intrinsic Neuronal Properties of Nucleus Accumbens Core and Shell Medium Spiny Neurons in Animals Prone to Sign- or Goal-Track

The "sign-tracking" and "goal-tracking" model of individual variation in associative learning permits the identification of rats with different cue-reactivity and predisposition to addiction-like behaviors. Certainly, compared to "goal-trackers" (GTs), "sign-trackers" (STs) show more susceptibility traits such as increased cue-induced relapse of drugs of abuse. Different cue- and reward-evoked patterns of activity in the nucleus accumbens (NAc) have been a hallmark of the ST/GT phenotype. However, it is unknown whether differences in the intrinsic neuronal properties of NAc medium spiny neurons (MSNs) in the core and shell subregions are also a physiological correlate of these phenotypes. We performed whole-cell slice electrophysiology in outbred male rats and found that STs exhibited the lowest excitability in the NAc core, with lower number of action potentials and firing frequency as well as a blunted voltage/current relationship curve in response to hyperpolarized potentials in both the NAc core and shell. Although firing properties of shell MSNs did not differ between STs and GTs, intermediate responders that engage in both behaviors showed greater excitability compared to both STs and GTs. These findings suggest that intrinsic excitability in the NAc may contribute to individual differences in the attribution of incentive salience. Significance StatementDuring associative learning, cues acquire predictive value, but in some instances, they also acquire incentive salience, meaning they take on some of the motivational properties of the reward. The propensity to attribute cues with incentive salience varies between individuals, and excessive attribution can lead to maladaptive behaviors. The "sign-and goal-tracking" model allows us to isolate these two properties and disambiguate the neurobiological processes that govern them. To our knowledge this is the first study characterizing passive and active membrane properties of MSNs in the NAc core and shell of STs and GTs, as well as IRs. These findings are meant to better inform investigations of the distinct role of the NAc in reward learning, particularly in the attribution of incentive salience and addiction predisposition.