Neurobiology of learning and memory
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Neurobiol Learn Mem · May 2012
Epigenetic regulation of reelin and brain-derived neurotrophic factor genes in long-term potentiation in rat medial prefrontal cortex.
Epigenetic mechanisms have recently been known to play fundamental roles in the regulation of synaptic plasticity, and learning and memory tasks in many brain regions, such as the hippocampus, the amygdala, the insular cortex. However, epigenetic mechanism in the medial prefrontal cortex (mPFC), also a crucial neural locus for the control of cognition and emotion, is not well known. The present study investigated the epigenetic regulation of two genes, reelin and brain-derived neurotrophic factor (bdnf), both play important roles in neural plasticity, in the mPFC. ⋯ Consistently, infusion of DNMT inhibitor, 5-azacytidine (5-azaC), or histone deacetylases (HDACs) inhibitor, sodium butyrate (NaB), into the mPFC could interfere with LTP-associated demethylation and acetylation of reelin and bdnf genes, and the induction of LTP as well. Long-term retention of trace fear memory, which is dependent on mPFC function, was also altered by administration of these inhibitors into the mPFC. These findings suggest that epigenetic regulation of DNA demethylation and histone acetylation of target genes, such as reelin and bdnf, might underlie the mechanisms of synaptic plasticity and memory retention in the mPFC.
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Neurobiol Learn Mem · Mar 2012
Brain activity associated with omission of an aversive event reveals the effects of fear learning and generalization.
During fear learning, anticipation of an impending aversive stimulus increases defensive behaviors. Interestingly, omission of the aversive stimulus often produces another response around the time the event was expected. This omission response suggests that the subject detected a mismatch between what was predicted and what actually occurred, thereby providing an indirect measure of cognitive expectancy. ⋯ These same regions also showed omission-related responses during the generalization test following highly expressive fearful faces. Finally, regression analysis on omission responses during the generalization test revealed correlations in offset-related SCRs and neural activity in the dorsomedial prefrontal cortex and posterior parietal cortex. Thus, converging psychophysiological and neural activity upon omission of aversive stimulation provides a novel metric of US expectancy, even to generalized cues that had no prior history of reinforcement.
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Neurobiol Learn Mem · Jan 2012
Loss of activity-dependent Arc gene expression in the retrosplenial cortex after hippocampal inactivation: interaction in a higher-order memory circuit.
The rodent hippocampus is well known for its role in spatial navigation and memory, and recent evidence points to the retrosplenial cortex (RSC) as another element of a higher order spatial and mnemonic circuit. However, the functional interplay between hippocampus and RSC during spatial navigation remains poorly understood. To investigate this interaction, we examined cell activity in the RSC during spatial navigation in the water maze before and after acute hippocampal inactivation using expression of two immediate-early genes (IEGs), Arc and Homer 1a (H1a). ⋯ Importantly, bilateral inactivation of hippocampus resulted in loss of behavior-induced Arc expression in RSC. Despite a lateralized effect in CA1, Arc expression was equivalently and bilaterally decreased in RSC of uni-TTX rats, consistent with a network level interaction between hippocampus and RSC. We conclude that the loss of hippocampal input alters activity of RSC neurons and compromises their ability to engage plastic processes dependent on IEG expression.
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Neurobiol Learn Mem · Jan 2012
Different types of exercise induce differential effects on neuronal adaptations and memory performance.
Different exercise paradigms show differential effects on various forms of memory. We hypothesize that the differential effects of exercises on memory performance are caused by different neuroplasticity changes in relevant brain regions in response to different exercise trainings. We examined the effects of treadmill running (TR) and wheel running (WR) on the Pavlovian fear conditioning task that assesses learning and memory performance associated with the amygdala (cued conditioning) and both the amygdala and hippocampus (contextual conditioning). ⋯ Injection of K252a, a TrkB kinase inhibitor, in the dorsal hippocampus or basolateral amygdala abolished the exercise-facilitated contextual or cued fear learning and memory performance, respectively, regardless of the types of exercise. In summary, our results supported that different types of exercise affect the performance of learning and memory via BDNF-TrkB signaling and neuroplasticity in specific brain regions. The brain region-specific neuronal adaptations are possibly induced by various levels of intensity/stress elicited by different types of exercise.
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Neurobiol Learn Mem · Jan 2012
Activation and role of the medial prefrontal cortex (mPFC) in extinction of ethanol-induced associative learning in mice.
Although the medial prefrontal cortex (mPFC) has been shown to be integrally involved in extinction of a number of associative behaviors, its role in extinction of alcohol (ethanol)-induced associative learning has received little attention. Previous reports have provided evidence supporting a role for the mPFC in acquisition and extinction of amphetamine-induced conditioned place preference (CPP) in rats, however, it remains unknown if this region is necessary for extinction of ethanol (EtOH)-induced associative learning in mice. ⋯ In order to confirm a functional role of the mPFC in regulating the extinction process, we then showed that electrolytic lesions of the mPFC following acquisition blocked subsequent extinction of EtOH-CPP. Together, these experiments indicate a role for the PL and IL subregions of the mPFC in processing changes of the EtOH-cue contingency, as well as in regulating extinction of EtOH-induced associative learning in mice.