Prethalamic Mechanisms Underlying Flexible Behavior in Aversive Contexts

Fast instinctive responses to environmental stimuli can be crucial for survival, but are not always optimal. Animals must balance rapid instinctive responses with the ability to adapt behavior based on experience, optimizing survival in changing environments. My talk will uncover the neural mechanisms enabling the suppression of instinctive fear reactions and the regulation of behavioral strategies in aversive contexts. We show that higher visual areas (plHVAs) mediate the suppression of instinctive escape behaviors in response to visual threats via a corticofugal pathway targeting the ventrolateral geniculate nucleus (vLGN). During learning, plHVA inputs drive plasticity in the vLGN, enhancing responses to threat stimuli through endocannabinoid-mediated modulation of inhibitory circuits. This learning induces plastic changes within vLGN, revealing a circuit-specific mechanism for overwriting instinctive behavior. Additionally, we demonstrate that vLGN serves as a key node for integrating cognitive and affective inputs to regulate behavioral strategies in aversive environments. vLGN activity, modulated by prior experience and internal fear states, governs decisions between safety and exploration. Inputs from retrosplenial cortex and ventromedial hypothalamus converge on vLGN to guide risk-related actions, allowing animals to flexibly respond to threats without compromising exploratory drive. Together, these findings reveal how cortical, hypothalamic and prethalamic circuits interact to enable experience-dependent suppression of instinctive responses and the selection of adaptive strategies in aversive contexts, with implications for understanding anxiety-related dysfunctions and potential treatments.