Adolescence marks a state of increased engagement of dopamine systems, a neurobiological state associated with increased reward-motivated behaviors. While increased dopamine signaling during this time period predominately supports adaptive developmental processes, such as exploration and reward learning, it can also propel risk taking behaviors associated with substance use and abuse. Prominent animal models have shown that engagement of dopamine systems and increased reward sensitivtycan increase plasticity and consolidation in hippocampal learning systems, resulting in enhanced memory for rewarding events. Critically, these enhancements in memory underlie the reinstatement of prior drug-related contexts and propel drug use. While a large rodent literature has focused on reward?s influence on hippocampal-dependent plasticity, relatively little work has characterized these processes in human adults or adolescents. We propose to study the influence of reward on memory consolidation and episodic memory throughout adolescence into early adulthood. We will study 90 14- to 25- year-old healthy subjects using multiple neuroimaging modalities. All participants will complete a reward memory paradigm, which will allow for the quantification of the influence of reward on episodic memory, i.e. a behavioral marker of hippocampal consolidation. Memory enhancements for reward will be associated with neural markers related to memory consolidation.
In Aim 1, we will characterize associations between reward-mediated memory enhancements and neural markers of consolidation in healthy adults, allowing us to translate and extend animal models into a human neuroscience framework.
In Aim 2, we will characterize these relationships throughout adolescence to better understand how adolescents heighted sensitivity to reward influences long-term memory representations throughout development. This work will provide a deeper understanding of how hippocampal plasticity is influenced by reward throughout adolescence, and bolster a foundation to better understand the vulnerability to substance abuse in this population.
Prominent animal models suggest that interactions between the mesolimbic dopamine system and hippocampus may underlie enhanced consolidation for reward-related memories. Prominent animal models have associated mesolimbic-hippocampal interactions with a variety of features of substance abuse, including drug relapse and craving. This circuit may be particularly relevant for increased vulnerability for substance abuse in adolescence, as there is increased engagement of mesolimbic system during this time period. While prior research has characterized these interactions in animal models, relatively little is known as to how these systems develop throughout early adolescence into adulthood in humans. This proposal examines the development of neural systems that mediate the influence of reward motivation on memory consolidation and episodic memory. These investigations provide an empirical model of how mesolimbic-hippocampal interactions contribute the persistence of reward memories, and will provide a foundation to study these circuits in individuals with or at risk for drug abuse. !
