Understanding the post-natal emergence and progression of episodic/hippocampal based and affective/amygdala based learning and memory systems in male and female animals can lead to significant advances in education, anxiety disoders and a detailed understanding of neural basis of learning and memory. We start off with the basic observation that learning and memory in children and young animals are particulary distinct when compared to adult mammalian counterparts. Our central hypothesis is that early in development, affective neural circuits dominate learning and that later, cognitive neural circuits emerge to further regulate learned behaviors. Moreover, the development and function of each these memory systems are influenced by perinatal gonadal hormones, resulting in sex differentiation of learning and memory. This hypothesis is grounded in the knowledge that late maturing hippocampal and prefrontal cortical circuits are fine-tuned to encode patterns of contextual-spatial elements and at test are capable to sufficiently retrieve this same pattern of elements.This pattern completion view of perceptual learning is combined with the knowledge that the basolateral and central amygdala microcircuits emerge earlier in development and are crucial for emotional learning including fear. We approach these questions by using standard and modified Contextual Fear Conditioning procedures in combination with neuroanatomical tools to create whole-brain functional neural acitivity maps underlying learning and memory across developmental lifespan of the male and female rat. These data will be used to create an open access database of all raw data, functional maps and group analytics. In addition, these data will be used to target inactivation of key neural pathways in the acquisition, retention and retriveal of contextual fear memories.
Anxiety disorders afflict 18% of the U.S. population making it a significant mental health problem relevant to the NIH mission. Given this, the onset of anxiety disorders is most prominent in females, typically emerges around developmental periods of pre- adolescence and adolescence. With maladaptive fear and disrupted cognitive function being key features of anxiety disorders, unraveling behavioral and neural mechanisms in developing learning and memory systems can lead to a deeper understanding of anxiety disorders in males and females. Lastly, central to our approach and consistent with the NIH's blueprint for neuroscience, we will create and disseminate whole brain functional neuroanatomical maps of the developing contextual fear learning systems.
