Prefrontal Limbic Areas Research Articles

Mirror trends of plasticity and stability indicators in primate prefrontal cortex

Research on plasticity markers in the cerebral cortex has largely focused on their timing of expression and role in shaping circuits during critical and normal periods. By contrast, little attention has been focused on the spatial dimension of plasticity-stability across cortical areas. The rationale for this analysis is based on the systematic variation in cortical structure that parallels functional specialization and raises the possibility of varying levels of plasticity. Here, we investigated in adult rhesus monkeys the expression of markers related to synaptic plasticity or stability in prefrontal limbic and eulaminate areas that vary in laminar structure. Our findings revealed that limbic areas are impoverished in three markers of stability: intracortical myelin, the lectin Wisteria floribunda agglutinin, which labels perineuronal nets, and parvalbumin, which is expressed in a class of strong inhibitory neurons. By contrast, prefrontal limbic areas were enriched in the enzyme calcium/calmodulin-dependent protein kinase II (CaMKII), known to enhance plasticity. Eulaminate areas have more elaborate laminar architecture than limbic areas and showed the opposite trend: they were enriched in markers of stability and had lower expression of the plasticity-related marker CaMKII. The expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, was also higher in limbic areas, suggesting that cellular stress correlates with the rate of circuit reshaping. Elevated markers of plasticity may endow limbic areas with flexibility necessary for learning and memory within an affective context, but may also render them vulnerable to abnormal structural changes, as seen in neurologic and psychiatric diseases.

EPA-1465 – Polygenic risk of depression and prediction of illness in families at high familial risk

Mood disorders, including depression and bipolar disorder, have a strong familial basis and unaffected offspring of affected individuals have a substantially increased lifetime risk of these and other psychiatric disorders. It is increasingly understood that risk is conferred through the cumulative effects of a number of common genetic variants each of low-effect size. Using data from the Psychiatric Genomics Consortium, we conducted polygenic risk profiling of cohorts of individuals with brain imaging (Bipolar Family Study) and/or cognitive data. We showed that increased polygenic risk of mood disorder is associated with functional abnormalities of ventral prefrontal limbic areas and with reduced connectivity, measured using diffusion tensor imaging (DTI). We discuss the utility of polygenic profiling for biomarker and mechanism discovery and its potential role in predicting disease-associated phenotypes and clinical illness.