Maturation of extinction behavior in infant rats: large-scale regional interactions with medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex.

The ability to express a behavior during the postnatal period may be related to developmental changes in the recruitment of particular neural systems. Here, we show that developmental changes in the functional interactions involving three cortical regions (the medial prefrontal cortex, orbitofrontal cortex, and anterior cingulate cortex) are associated with maturation of extinction behavior in infant rats. Postnatal day 17 (P17) and P12 pups were trained in a straight-alley runway on an alternating schedule of reward and nonreward [patterned single alternation (PSA)] or on a pseudorandom schedule of partial reinforcement (PRF); the pups were then injected with fluorodeoxyglucose (FDG) and shifted to continuous nonreward (extinction). Handled control groups exposed to the same training environment but not trained on a particular schedule were included. Among P17 pups, extinction proceeded faster in PSA pups relative to PRF pups. No differences were found between P12 groups. FDG uptake, an index of acute changes in functional activity, was quantified in the three cortical regions and 27 other brain regions of interest. A multivariate covariance analysis, seed partial least squares, revealed that functional relationships involving the three cortical regions and large-scale systems of regions throughout the rostrocaudal extent of the brain changed with training in P17 pups. The cortical regions were primarily uncoupled in the younger group. The data suggest that functional maturation of the frontal cortical regions and their interactions with other brain systems are related to the maturational shift in behavior.

Extinction of behavior in infant rats: development of functional coupling between septal, hippocampal, and ventral tegmental regions.

Learning of a behavior at a particular age during the postnatal period presumably occurs when the functional brain circuit mediating the behavior matures. The inability to express a learned behavior, such as inhibition, may be accounted for by the functional dissociation of brain regions comprising the circuit. In this study we tested this hypothesis by measuring brain metabolic activity, as revealed by fluorodeoxyglucose (FDG) autoradiography, during behavioral extinction in 12- and 17-d-old rat pups. Subjects were first trained on a straight alley runway task known as patterned single alternation (PSA), wherein reward and nonreward trials alternate successively. They were then injected with FDG and given 50 trials of continuous nonreward (i.e., extinction). Pups at postnatal day 12 (P12) demonstrated significantly slower extinction rates compared to their P17 counterparts, despite the fact that both reliably demonstrated the PSA effect, i.e., both age groups distinguished between reward and nonreward trials during acquisition. Covariance analysis revealed that the dentate gyrus, hippocampal fields CA1-3, subiculum, and lateral septal area were significantly correlated in P17 but not P12 pups. Significant correlations were also found between the lateral septal area, ventral tegmental area, and the medial septal nucleus in P17 pups. Similar correlative patterns were not found in P12 and P17 handled control animals. Taken together, these results suggest that septal, hippocampal, and mesencephalic regions may be functionally dissociated at P12, and the subsequent maturation of functional connectivity between these regions allows for the more rapid expression of behavioral inhibition during extinction at P17.

Extinction after regular and irregular reward schedules in the infant rat: influence of age and training duration.

Greater persistence in extinction is observed following inconsistent reward compared to that observed following consistent reward, an effect termed the partial reinforcement extinction effect (PREE). We report three experiments in which the extinction rates of random partially reinforced (PRF) or continuously reinforced (CRF) infant rat pups were compared to the extinction rate of pups trained with an alternative and regular schedule of partial reinforcement, known as patterned single alternation (PSA). In PSA, subjects learn to alternate speed of responding in anticipation of the regular alternation of reward and nonreward trials in the straight alley runway. In Experiment 1, 17-day-old PSA subjects showed CRF-like extinction rates; whereas in Experiment 2, in which extinction was initiated early in training prior to the onset of the PSA discrimination, PSA subjects showed prolonged, PRF-like extinction curves. In contrast, 12-day-old pups in Experiment 3 showed no reward-schedule-related differences in extinction, despite differences in behavior during acquisition. These results prompt a modification of Amsel's (1962) model of discrimination learning, and suggest the existence of a dissociation between different types of reward-related expectancies in the younger subjects.