The tendency to respond in similar ways to different situations, known as generalization, can be adaptive or maladaptive, depending on the context. For example, feeling apprehension when walking down a dark alley in any place in the world can be important for survival; however, displaying fear in well-lit streets is detrimental. These examples illustrate that the context or surroundings can signal when fear generalization is adaptive. The ventral hippocampus, an area involved in memory and anxiety, is in a key position to code contextual valence and use this information to generate selective versus generalized responses. Yet little is known about how this area modulates the expression of these behaviors. The goal of this project is to determine if different cells types within the ventral hippocampus modulate the expression of selective vs. generalized emotional responses. Understanding the mechanisms that control the selectivity of emotional behavior is extremely important because it can serve to explain anxiety behaviors, such as phobias or post-traumatic stress, where fear is continuously expressed in inappropriate contexts. Moreover, understanding the computations underlying generalization extends beyond emotional learning, having potential impact on artificial intelligence and machine learning. To address this question, this project uses cutting-edge techniques, including in vivo recordings of selective populations of cells while animals are learning. Since UTSA is a minority serving institution, this research also provides training opportunities to underrepresented groups and inform the community at large about current scientific issues through an ongoing podcast that serves to showcase prominent neuroscientists.
The ventral hippocampus has reciprocal connections with the basolateral amygdala, an area involved in fear learning and extinction, and it is the main hippocampal region sending projections to the prelimbic and infralimbic cortices, areas of the medial prefrontal cortex involved in fear expression and extinction, respectively. Additionally, ventral hippocampus principal cells display large, overlapping firing fields that are ideal for generalization processes. The overarching hypothesis of this proposal is that the ventral hippocampus modulates selective vs. generalized responses though the activity of distinct subpopulations of projection neurons with different physiological and computational properties. This idea is assessed by combining in vivo single unit and local field potential recordings along with pathway-specific chemogenetic silencing/activation and in vitro patch clamping techniques along with optogenetic circuit analysis to answer the following questions: 1) How do subpopulations of ventral hippocampal cells respond and synchronize with target regions when animals discriminate or generalize emotional responses? 2) What is the role of different ventral hippocampus projection cells in generalization/discrimination and how do ventral representations change when distinct subpopulations are selectively activated or inhibited? 3) What are the computational and synaptic properties of different ventral hippocampus projection cells? Since too narrow or too broad generalization can have extremely negative consequences for survival, understanding the neural mechanisms that produce fine calibration of generalization processes is very important.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
