UC Riverside

The mental state of fear together with its related behavioral, physiological, and perceptual responses to threatening stimuli, is a highly conserved response in the animal kingdom that serves important functions for an animal’s survival. One of the challenges in modern neuroscience is to understand the mechanisms underlying how brain networks resolve ambiguous contextual information for appropriate valence determination and, subsequently, guide appropriate behavior responses. Fear based behaviors have been extensively studied over a hundred years using classical Pavlovian fear conditioning, in which a conditioned stimulus (CS) such as context is paired with an inherently aversive stimulus (US), like a mild foot shock. This form of associative learning has been used extensively to study the neural correlates of fear including the circuit-level, cellular-level, and molecular-level mechanisms of learning and memory. While it is well established that fear conditioning is encoded primarily in basolateral amygdala, the subsequent modulation of fear behavior involves a broader fear modulation circuit. There is strong evidence for the involvement of infralimbic (IL) and prelimbic (PL) subdivisions of prefrontal cortex (PFC) in fear memory modulation; however, the circuit-level mechanisms guiding appropriate fear responses are unclear. Current studies reveal that neurons in both IL and PL are active across fear discrimination learning. For example, fear conditioning triggers neuronal representation for CS+ specifically in PL but not in IL. In addition, differential fear conditioning triggers subtle and distinctive temporal patterns of neuronal representations of CS- in both PL and IL. Viral targeting of prefrontal cortex subdivisions with a specific inhibitor of memory consolidation demonstrated that both PL and IL are separately coding critical information during fear discrimination learning, which is consistent with prior data. In addition, neurons in PL projecting to BLA are also highly involved in coding information critical to learning appropriate balancing of fear responses. These data suggest that while there is functional division between IL and PL as previously suggested, both regions are necessary during differential fear discrimination learning. Furthermore, IL cannot compensate for impaired PL function, and PL cannot compensate for impaired IL function under the condition that both regions remain engaged during learning.