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Learning and Anxiety in Amygdala-based Neural Circuits

Periodic Reporting for period 3 - LearnAnx_CircAmyg (Learning and Anxiety in Amygdala-based Neural Circuits)

Reporting period: 2020-09-01 to 2022-02-28

We have limited understanding of the mechanisms that underlie complex learning in emotional situations, and how these processes can go awry and result in mal-adaptive behaviors and even psychopathologies. In this project we develop models of complex behaviors that are motivated by either positive or negative reinforcers, and examine how they are governed and coded in neural networks. We focus on the pathway between the Amygdala and the prefrontal-cortex, as it is a main network that underlies learning and memory-formation in emotional contexts. It is also a main network that is implicated in almost all psychiatric conditions, and mainly in anxiety and post-trauma disorders. We record neural activity using deep multi-contact arrays to unveil the coding schemes embedded in these high-dimensional networks, and develop models of learning that are highly evolved in primates, such as rule-learning, generalization (the ability to abstract) and social interactions. The development of more complex models of behavior is crucial and is the next logical and required step in achieving translation of animal models for anxiety disorders, as well as in understanding basic mechanisms behind the rich repertoire of primates’ emotional behaviors.
We developed several behavioral models and were able to record neural activity during performance of these behavior. Importantly, we were able to unveil coding mechanisms in the primate amygdala that use temporal sequences of neural activations to enable rehearsal of a recently acquired emotional memory, either positive or negative. This result demonstrates directly that a recent learned emotional event is ‘rehearsed’ in the brain to allow its consolidation into memory. In a parallel project, we looked for difference between the human amygdala and the non-human-primate amygdala, and demonstrated that the ability of the neurons to code information is richer in humans, yet more robust in non-humans. This finding is one of the first to tell us why humans might have a better ability learn and generalize, but are also more vulnerable to “bugs” in the code, that might lead to psychopathologies. In addition, we developed a new framework of complex rule-learning, and show how networks in the prefrontal cortex and subcortical regions contribute in complementing manners to learning new rules, and develop coding schemes that can later be used to generalize behavior to similar rules.
The development of new models for complex mal-adaptive learning is a much required progress beyond the current models for anxiety/trauma, mostly based on classical conditioning. Because human psychopathology is clearly more complex than simple associative learning, such understanding of how the brain learns and codes for these elaborated behaviors is a must. We made clear progress in these aspects. We are now finalizing a project that shows a connection between social behaviors, with a focus on eye-gaze unique to primates, and emotional learning. This project shows that both social and emotional learning likely developed in the same circuits, with similar mechanisms for valence-based behaviors. In the time remaining in the project we will develop a closed-loop approach that allows us to test directly coding in the primate amygdala of emotional learning, and even manipulate and modulate it to achieve better control of the process nad hopefully suggest translational impact.