Extinction of Behavior in Infant Rats: Development of Functional Coupling Between Septal, Hippocampal, and Ventral Tegmental Regions

Abstract

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.

Animal model of posterior cingulate cortex hypometabolism implicated in amnestic MCI and AD

“…data and cell counts in the Nissl-stained slides were examined using Student's t tests. Furthermore, within each group, the functional intercorrelations between the PCC and other brain regions were analyzed by computing inter-regional activity correlations (Nair and Gonzalez-Lima, 1999). Activity values for both control and sodium azide-treated groups were analyzed with Pearson's correlation coefficients.…”

The effects of selective ibotenate lesions of the hippocampus on conditioned inhibition and extinction

“…The results of recent studies have also provided autoradiological evidence that seems consistent with the results that are reported here. For example, Nair and Gonzalez-Lima (1999) reported that rat pups show significantly slower rates of extinction in a runway task at Postnatal Day 12 than at Postnatal Day 17. Using brain metabolic mapping techniques, these researchers found that improvement in extinction performance between Postnatal Days 12 and 17 was positively correlated with increased metabolic activity in the CA1 and CA3 cell fields of the hippocampus.Increased activity in these hippocampal cell fields was not reported in an earlier study that used a similar metabolic analysis of the brain activity of adult rats during standard Pavlovian CI training (e.g., McIntosh & Gonzalez-Lima, 1995).…”

Dual Circuitry for Odor-Shock Conditioning during Infancy: Corticosterone Switches between Fear and Attraction via Amygdala

“…While the amygdala continues to develop through adolescence, nuclei are distinct by P7 and responsive to olfactory information during the early neonatal period (Schwob et al, 1984;Berdel et al, 1997;Morys et al, 1999;Nair and Gonzalez-Lima, 1999;Berdel and Morys, 2000;Bouwmeester et al, 2002;Wilson, 2003). However, at this age, minimal connections exist between the amygdala and other brain areas considered important in fear conditioning, such as the prefrontal cortex and hippocampus (Nair and Gonzalez-Lima, 1999;Bouwmeester et al, 2002).…”