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2015 Conte Center Seed Grant Awardees
The Conte Center @ UCI is pleased to announce the awardees for the 2015 Seed Grants. The awarded proposals were selected from a highly competitive pool of UCI researchers. With the support of the ICTS an extensive external review was conducted to select the preeminent proposals. Each of the proposals selected expands the Conte Center’s ability to meet their mission to address the complex developmental mechanisms responsible for adolescent vulnerability to emotional and cognitive disorders.
For more information about the Conte Center @ UCI please visit http://contecenter.uci.edu/
Professor Bruce McNaughton, PhD
Environmental enrichment effects on neural systems dynamics underlying memory and decision making
Environmental enrichment (EE) is the exposure to a variety of enhanced social and non-social stimuli that modify the brain across different levels of organization. EE during adolescence leads to persistent performance improvement on various cognitive tasks. Although the effects of EE on the brain have been thoroughly characterized in rodent models at the molecular, cellular and behavioral level, very little is known about the effects at the neural systems level. The aim of the current pilot study is to assess persisting effects of EE during adolescence on global brain dynamics and on the hippocampo-neocortical networks supporting memory and action selection. We will expose adolescent rats (postnatal day 21) to an EE paradigm for 3 months. EE will include housing in a large enclosure, equipped with daily exchanged objects, odors and food items, as well as audiovisual stimulation. Control animals will be home-caged. Following EE, rats will be implanted with recording electrode arrays in ventral hippocampus and medial prefrontal cortex. One month later, the rats will undergo 24-hr recording to assess the effects of EE on brain dynamics related to memory consolidation processes. Subsequently, neural activity will be recorded during performance on a reversal learning task on a Y-maze, which has been previously found to be enhanced following EE. With this we will assess neural processes related to action selection (decision making). EE has beneficial effects on the functional outcomes of cerebral palsy and stroke in humans, and slows the progression of pathological changes in a rodent model of Alzheimer's disease. Findings from this study will begin to provide mechanistic understanding of EE-induced persistent changes in brain dynamics and lay the groundwork for a much larger NIH proposal on systems effects of EE in early development. These results are ultimately expected also to help guide public policy.
Persistent effects of developmental cannabinoid exposure on oxytocin-dependent endocannabinoid signaling in social reward
In a study that is about to be published (Wei et al., 2015), we have shown that the marijuana-like neurotransmitter, anandamide, controls the rewarding value of social interactions in mice. The present proposal addresses the question of whether this regulatory mechanism might be affected by exposure to cannabinoid drugs during adolescence. This question is important because of the spread of recreational marijuana use among teenagers as well as marijuana’s recent medicalization in many States of the Union. Underscoring this point, the National Institute on Drug Abuse (NIDA) has recently issued a Request for Applications (RFA) that calls for investigation into the effects of cannabinoids on the developing brain. We intend to respond to this RFA with an R01 application aimed at testing the hypothesis that exogenous activation of CB1 cannabinoid receptors during adolescence impairs anandamide-mediated regulation of social reward later in life. In support of this hypothesis, we found in preliminary experiments that a 2-week treatment with the cannabinoid receptor agonist WIN-55212-2 (WIN) in adolescent mice (post natal day, PND, 30-43) abolished social reward in early adulthood (PND 58). In the present application, we request funding to conduct two pilot experiments that are needed to seed Specific Aims 2 and 3 of our planned R01 proposal.