Biology subjects

Balleine, B.

Publications and source records attributed to Balleine, B..

5 recordsLinked to original sources

bioRxiv2026

Intratelencephalic neurons in the medial prefrontal cortex mediate the acquisition of goal-directed actions.

The medial prefrontal cortex (mPFC) and its connections with the posterior dorsomedial striatum are implicated in goal-directed learning, but the specific mPFC cell types involved have not been clearly established. The current study investigated mPFC intratelencephalic (IT) and pyramidal tract (PT) neuron involvement in goal-directed learning. In Cre-driver mouse lines, we mapped bilaterally projecting IT neurons and unilaterally projecting PT neurons from mPFC to dorsal striatum and showed that chemogenetic inhibition of IT, but not PT neurons, attenuated goal-directed learning. We then demonstrated training induced elevations in pERK signaling in IT neurons, which were transient in superficial mPFC layers, and more persistent in deeper layers. This was associated with plasticity in deep layer IT neurons, reflected in a shift towards excitatory over inhibitory synaptic inputs. Together, these data suggest that goal-directed learning influences synaptic input and downstream plasticity markers in mPFC IT neurons, and this functionally contributes to goal-directed learning.

neuroscience↗

bioRxiv2026

The motivational control of instrumental performance by nutrient-specific appetites depends on incentive learning

Considerable evidence suggests that the motivational control of instrumental action depends on incentive learning; i.e., on the opportunity to learn how the value of the consequences or outcome of an action, (e.g., a specific food) varies under different motivational conditions (e.g., under different degrees of hunger). The current study investigated whether learning the values of high-protein and high-carbohydrate rewards under different degrees of protein and carbohydrate appetite is also necessary for these nutrient-specific appetites to exert control over instrumental performance. Experiment 1 gave differing consummatory experience to whey protein and polycose carbohydrate outcomes under protein and carbohydrate appetite and found that, without the opportunity for incentive learning, the performance of actions earning these outcomes was insensitive to a shift in appetite. However, once the opportunity for incentive learning was provided, the rats increased their instrumental performance on a lever that earned the whey outcome relative to the polycose lever when protein hungry and on the polycose lever relative to the whey lever when carbohydrate hungry. Experiment 2 assessed how these nutrient-specific states exerted this control; whether, once learned, nutrient values were immediately controlled by nutrient appetite or whether this was based on conditional control acquired during experience with the outcomes under different nutrient appetites. We found that exposure to an outcome under a single nutrient-specific state was not sufficient to establish state-specific control. Instead, establishing the conditional control of outcome value required exposure to both the whey and polycose outcomes under both protein and carbohydrate appetites.

animal behavior and cognition↗

bioRxiv2022

Goal-directed action is transiently impaired in an hAPP-J20 mouse model of Alzheimer's disease, and in aging male mice regardless of genotype

Cognitive-behavioural testing in preclinical models of Alzheimers disease has typically been limited to visuo-spatial memory tests and has failed to capture the broad scope of deficits patients also display in goal-directed action control. The current study addresses this gap by providing the first comprehensive investigation of how goal-directed actions are affected in a transgenic mouse model of Alzheimers disease. Specifically, we tested outcome devaluation performance - a popular test of goal-directed action - in male and female human amyloid precursor protein (hAPP)-J20 mice. Mice were first trained to press a left and right lever for unique pellet and sucrose outcomes respectively (counterbalanced) over four days. On test, mice were fed one of the two outcomes to reduce its value via sensory specific satiety and subsequently given a choice between levers. Goal-directed action was intact for 36-week-old wildtype mice of both sexes, because they responded more on the lever associated with the still-valued outcome than that associated with the devalued outcome (i.e. Valued > Devalued). Goal-directed action was impaired (Valued = Devalued) for J20 mice of both sexes, and for 52-week-old male mice regardless of genotype. Following an additional 4 days of lever press training (i.e., 8 days lever pressing in total), outcome devaluation was intact for all mice regardless of age or genotype. Immunohistochemical analysis revealed that increased microglial expression in the dorsal CA1 region of the hippocampus was associated with poorer outcome devaluation performance on initial tests, but not with tests performed after 8 days of lever pressing. Together, these data demonstrate that goal-directed action is transiently impaired in J20 mice of both sexes and in aging male mice regardless of genotype, and that this impairment is related to neuroinflammation in the dorsal CA1 region of the hippocampus.

animal behavior and cognition↗

bioRxiv2022

Striatal dopamine encodes the relationship between actions and reward

Although the role of striatal dopamine in Pavlovian conditioning and in habits has been reasonably well described, relatively little is known about its function in goal-directed action. In this study we trained hungry rats on two lever press actions for distinct food outcomes and recorded dopamine release in the dorsomedial striatum as these action-outcome associations were encoded and subsequently degraded. During initial training the lever press actions generated bilateral dopamine release that was found to reflect the predicted action value. This value was updated by the prediction error generated by the feedback produced by contact with the outcome, or its absence, after the press. Importantly, hemispheric dopamine release became increasingly lateralized across the course of training, with greater release in the hemisphere contralateral to the press. Using video analysis and multiple different measures, we could find no evidence that the degree of lateralized release was associated with movement; rather, we found that it tracked the strength of the action-outcome association, increasing and decreasing with increments and decrements in the contingency between specific actions and their consequences. Similar results emerged whether the rewards were delivered on ratio or interval schedules of reinforcement and whether we used unpaired outcome delivery or outcome-identity reversal to modify the specific contingencies. These findings suggest that, whereas moment-to-moment fluctuations in action value are reflected in bilateral dopamine release, a second signal broadcasts the overall strength of specific action-outcome relationships via the difference between contralateral and ipsilateral release during actions.

neuroscience↗

bioRxiv2020

Medial Orbitofrontal Cortex Regulates Instrumental Conditioned Punishment, but not Pavlovian Conditioned Fear

Bidirectionally aberrant medial orbitofrontal cortical (mOFC) activity has been consistently linked with compulsion and compulsive disorders. Although rodent studies have established a causal link between mOFC excitation and compulsive-like actions, no such link has been made with mOFC inhibition. Here we use excitotoxic lesions of mOFC to investigate its role in sensitivity to punishment; a core characteristic of many compulsive disorders. In our first experiment, we demonstrated that mOFC lesions prevented instrumental conditioned punishment learning in a manner that could not be attributed to differences in Pavlovian conditioned fear. We then showed that increasing the frequency of punishing outcomes allowed mOFC-lesioned animals to overcome their initial deficit. Our second experiment demonstrated that the retrieval of instrumental punishment is also mOFC-dependent, as mOFC lesions prevented the extended retrieval of punishment contingencies relative to shams. In contrast, mOFC lesions did not prevent the re-acquisition of conditioned punishment that was learned prior to lesions being administered. Together, these results reveal that the mOFC does indeed regulate punishment learning and retrieval in a manner that is disassociated from any role in Pavlovian fear learning. These results imply that aberrant mOFC activity may contribute to the punishment insensitivity that is observed across multiple compulsive disorders.

neuroscience↗