The Neuronal Hypofunction of Subdivisions of the Prefrontal Cortex Shows Differential Effects on Contingency Judgment Learning to Gauge Fear Responses.

Previous studies have indicated that the infralimbic (IL) and prelimbic (PL) subdivisions of the medial prefrontal cortex (mPFC) serve as critical modulators of fear suppression and expression. Although significant research has been conducted on the extinction of conditioned fear, the mechanisms underlying contextual fear discrimination learning, a form of contingency judgment learning, remain inadequately understood. Our investigation aimed to explore the influence of epigenetic regulation associated with cyclic AMP-response element binding protein (CREB)-dependent long-term memory encoding within the IL and PL on contextual fear discrimination.

Prefrontal multistimulus integration within a dedicated disambiguation circuit guides interleaving contingency judgment learning.

Understanding how cortical network dynamics support learning is a challenge. This study investigates the role of local neural mechanisms in the prefrontal cortex during contingency judgment learning (CJL). To better understand brain network mechanisms underlying CJL, we introduce ambiguity into associative learning after fear acquisition, inducing a generalized fear response to an ambiguous stimulus sharing nontrivial similarities with the conditioned stimulus.

Differential fear conditioning generates prefrontal neural ensembles of safety signals.

Fear discrimination is critical for survival, while fear generalization is effective for avoiding dangerous situations. Overgeneralized fear is a typical symptom of anxiety disorders, including generalized anxiety disorder and posttraumatic stress disorder (PTSD). Previous research demonstrated that fear discrimination learning is mediated by prefrontal mechanisms.

Long-Lasting Effects of Prenatal Ethanol Exposure on Fear Learning and Development of the Amygdala.

Prenatal ethanol exposure (PrEE) produces developmental abnormalities in brain and behavior that often persist into adulthood. We have previously reported abnormal cortical gene expression, disorganized neural circuitry along with deficits in sensorimotor function and anxiety in our CD-1 murine model of fetal alcohol spectrum disorders, or FASD (El Shawa et al., 2013; Abbott et al.

Rubinstein-Taybi Syndrome and Epigenetic Alterations.

Rubinstein-Taybi syndrome (RSTS) is a rare genetic disorder in humans characterized by growth and psychomotor delay, abnormal gross anatomy, and mild to severe mental retardation (Rubinstein and Taybi, Am J Dis Child 105:588-608, 1963, Hennekam et al., Am J Med Genet Suppl 6:56-64, 1990). RSTS is caused by de novo mutations in epigenetics-associated genes, including the cAMP response element-binding protein (CREBBP), the gene-encoding protein referred to as CBP, and the EP300 gene, which encodes the p300 protein, a CBP homologue.