Ibec Seminar. Sara Mederos
Brainwide circuits for adaptive decisions in response to threat
Sara Mederos, neuroscientist and Ramón y Cajal group leader of NeuCompLab at the Hospital del Mar Research Institute
To understand adaptive behavior, we must understand how decisions are computed and updated through experience. For example, when facing a potential threat, animals may initially rely on instinctive responses, such as escape, yet with experience they can suppress these reactions as the environment is reinterpreted. In this talk, I will show how these transformations arise from interactions between cortical and subcortical circuits that dynamically reshape decision variables in aversive contexts.
Using an ethologically grounded paradigm in which mice escape from an overhead looming stimulus that mimics an aerial predator, I will show that repeated exposure leads to suppression of this instinctive response. We find that higher visual areas instruct this learning through projections to the inhibitory ventrolateral geniculate nucleus (vLGN). Neural population recordings reveal that specific vLGN neurons increase their activity across learning and are necessary for the expression of escape suppression, indicating that cortical inputs instruct learning, while plasticity within vLGN implements the learned behavioral change.
I will then extend this framework to show how vLGN integrates inputs from retrosplenial cortex and hypothalamic circuits to regulate decisions between safety and exploration. These pathways carry distinct signals related to prior experience and internal state, and their coordinated activity shapes when animals decide to leave safety. ogether, these results reveal circuit mechanisms through which experience reshapes decision-making in aversive environments.
Finally, I will present ongoing work showing how acute stress induces persistent changes in hippocampal dynamics, linking experience-dependent updating of threat with longer-lasting circuit adaptations that may be relevant for anxiety and PTSD.
Sara Mederos is a neuroscientist and Ramón y Cajal group leader of NeuCompLab at the Hospital del Mar Research Institute in Barcelona (neucomplab.com). She trained in
Biochemistry and Neuroscience and completed her PhD in Perea’s lab at the Instituto Cajal (CSIC), where she studied communication between neurons and astrocytes, contributing to
demonstrate that these cells actively participate in synaptic plasticity, learning, and goaldirected behaviour (Glia, 2019; Nature Neuroscience, 2021). During this period she also developed short research stays at the Buzsáki Lab (NYU) and the Ponomarenko Lab (HHU Düsseldorf). She subsequently developed her postdoctoral research in Hofer’s lab at the
Sainsbury Wellcome Centre, University College London, and later as an independent PI supported by a Wellcome Trust Early Career Award, where she dissected the neuronal circuits and mechanisms underlying how experience and learning can modify instinctive responses such as fear (Science, 2025). Her laboratory studies how the brain integrates information about the environment, prior experience, and internal states to make flexible decisions. Her research integrates advanced neuroscience techniques, including in vivo electrophysiology in freely moving mice, optogenetics, in vitro electrophysiology, and serial-section two-photon imaging, to dissect the neural circuits underlying flexible decision-making. This work has provided new insights into how cortical and subcortical circuits interact to support learned safety and adaptive behaviour. Her research is supported by competitive international funding from the European Research Council, the Wellcome Trust, the AEI, the BBRF, and the BBVA Foundation. Among other recognitions, she has received the FENS EJN Young Investigator Prize, the Janett Rosenberg Trubatch Career Development Award, and the L’Oréal-UNESCO For Women in Science Spain Award, and was selected as a finalist for the Eppendorf & Science Prize for Neurobiology
