DESCRIPTION (provided by applicant): The long-term objective of the application is to understand how emotional experiences alter memory acquisition and consolidation processes in the forebrain. The PI was instrumental in developing recent technological advances that allow powerful within-animal experimental designs in imaging plasticity-related genes expression in large groups of neurons across multiple brain regions. Applying this method (catFISH) the proposal outlines a series of experiments that can identify emotion-induced changes in the composition of neuronal groups expressing Arc and H1a, two activity-regulated genes that are necessary for memory consolidation. We will examine a two-part hypothesis: 7 Emotional spatial learning changes long term memory-related information processing in CA1 and projecting to it parts of CA3, perirhinal (PRh, area 35) and lateral entorhinal cortex (LEC). 7 Activation of the basolateral amygdala (BLA) during emotional learning enables changes in information processing induced by an emotional experience in CA1 and projecting to it parts of CA3, PRh and LEC. In Experiment 1 we will manipulate the emotional valence of a spatial context and assess the amount of overlap of Arc/H1a+ neurons in the hippocampal system induced by that spatial context when it is emotionally neutral, and when it is paired with an aversive event (contextual fear conditioning). Evidence that different Arc/H1a-expressing neuronal groups are activated when a place is emotionally-neutral and when the same place is paired with shock (low overlap) will suggest that during emotional learning the hippocampal system does not simply create contextual representation, but it has a more general mnemonic role that parallels its involvement in non-emotional learning. Observing low overlap in the hippocampus and projecting to it parts of perirhinal and lateral entorhinal cortex will indicate that emotional learning modulates information processing in the hippocampal system at multiple levels. We will combine intracranial drug infusions with the catFISH method to further investigate whether low overlap in the hippocampus during emotional learning is modulated by activation of the BLA. In a first test of this hypothesis the BLA will be inactivated and overlap will be assessed as in Experiment 1. Our hypothesis will be supported if inactivating the BLA before contextual fear conditioning results in high overlap in CA3 and CA1, similar to that of rats that have explored the context twice, but have not received footshock in it. The findings of the proposed research will significantly advance our understanding by answering two fundamental questions: 1) Are emotionally-influenced changes in spatial memory representations unique to the hippocampus, or are they distributed across the hippocampus and areas of perirhinal and lateral entorhinal cortex projecting to it? 2) Do emotionally-influenced changes in spatial memory representations depend on activation of the basolateral amygdala (BLA)? PUBLIC HEALTH RELEVANCE This basic science project proposes to investigate how emotional learning and resulting activation of the basolateral amygdala affects information processing in the hippocampal system. The resulting findings will be sure to inspire a very active area in public health in the coming decade. Disruption of emotion-influenced processes, including memory, are common in mood and psychiatric disorders such as post traumatic stress disorder, anxiety, depression, schizophrenia, phobias and manias. Understanding how emotion alters ongoing information processing and memory consolidation will enable more targeted studies of the mechanisms that are abnormal in these disorders and will provide a framework for testing genetic models and devising successful treatments. However, this is a basic science proposal and direct applicability to public health will depend upon follow-up applied studies.
|Effective start/end date||5/15/09 → 4/30/12|
- National Institutes of Health: $220,500.00
- National Institutes of Health: $183,750.00