This Week in The Journal

Reward and Extinction Memories in vmPFC

Brandon L. Warren, Michael P. Mendoza, Fabio C. Cruz, Rodrigo M. Leao, Daniele Caprioli, et al.

Animals that have learned an operant behavior such as pushing a lever to receive food eventually stop performing the behavior if the reward is no longer delivered. The association between action and reward is not forgotten, however. Instead, the animal forms a second memory, the extinction memory, that the reward is no longer available. Some experiments have suggested that activity in the dorsal medial prefrontal cortex (dmPFC) promotes operant behaviors, whereas activity in ventral mPFC (vmPFC) inhibits these behaviors after extinction. Contradictory evidence also exists, however. For example, while some studies found that broad inhibition of vmPFC reinstated drug seeking after extinction, others found that it reduced drug seeking.

To reconcile these results, Warren et al. hypothesized that different neuronal ensembles in vmPFC encode operant reward and extinction memories. To test this hypothesis, they used rats that express β-galactosidase under the control of the Fos promoter, which is regulated by neuronal activity. In these rats, neuronal activity increases expression of β-galactosidase, which converts the pro-drug Daun02 into a toxic molecule. Thus, Daun02 delivery kills recently activated neurons. These rats were trained to press a lever for food, and lever pressing was then extinguished in half the rats. On the next day, all rats were returned to the training chamber to activate ensembles encoding reward or extinction memories, and then Daun02 was delivered to vmPFC to kill activated neurons. Remarkably, Daun02-treated rats in which lever pressing had been extinguished showed more lever pressing than vehicle-treated controls when tested three days later, while Daun02-treated rats in which the behavior had not been extinguished showed less lever pressing than controls. Global inactivation of vmPFC with GABA receptor antagonists had no effect on lever pressing regardless of whether the behavior had been extinguished, however.

These results suggest that neuronal ensembles encoding food reward memories and ensembles encoding extinction memories are both present in the vmPFC. More broadly, the results demonstrate that global inactivation of a brain area can mask the effects of inactivating ensembles involved in a specific behavior. They thus emphasize the importance of using more precise manipulations to reveal brain function.

Hedonic Representations of Odors during Development

Rosemarie E. Perry, Syrina Al Aïn, Charlis Raineki, Regina M. Sullivan, and Donald A. Wilson

(see pages 6634–6650)

Odors vary greatly in their hedonic properties. Although some odors, such as predator urine, are innately aversive, most odor preferences are shaped by experience and associations. Pleasant or aversive associations, even those formed in early childhood, can shape food preferences and influence social affiliations throughout life. Yet surprisingly little is known about how the hedonic properties of odors are represented in the brain.

Patterns of correlated activation across brain areas differed for responses to male and maternal odors at P23. See Perry et al. for details.

To address this question, Perry et al. used 2-deoxyglucose autoradiography to label brain areas activated when rat pups were exposed to maternal or male odors. These odors were chosen because their hedonic properties depend on rearing conditions. Rat pups are normally attracted to the odor of any lactating female, which is dominated by a single component (caecotrophe). If production of this component is suppressed by feeding dams a special chow, pups are no longer attracted by the odor of other dams. Attraction to male odor also depends on rearing conditions. Pups raised without a father show aversive responses to male odor, whereas rats raised with a father are attracted to male odor.

Neural responses to maternal and male odors increased from postnatal day 7 (P7) to weaning (P23) in pups raised exclusively with their mothers fed normal chow. At P7, responses were present mainly in the olfactory bulb, anterior piriform cortex, and hippocampal CA1. At P14, activation in anterior piriform cortex had increased, and male odor activated additional areas—specifically the posterior piriform cortex and medial and lateral amygdala. These areas became activated by maternal odor at P23, at which time both odors activated orbitofrontal cortex (OFC) as well. Suppressing caecotrophe production in dams reduced activation of CA1, OFC, and lateral amygdala when their pups were exposed to normal maternal odor. Raising pups with their fathers produced more dramatic changes, reducing responses to male odors in all areas except the olfactory bulb.

These results suggest that neural representations of maternal and male odors expand during the first few postnatal weeks in rats. The fact that responses in multiple areas decreased when the hedonic properties of odors changed suggests that the representation of such properties is distributed across these areas. Future work should examine the nature of this encoding in more detail.