Role of Organic Anion Transporter 1 in the modulation of structural and functional plasticity in the hippocampus.

• Applicant: Professorin Dr. Daniela Mauceri
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 570478409

Neuroplasticity is defined as the capacity of the central nervous system (CNS) to adapt to stimuli through functional or structural reorganization of its connections, enabling cognitive processes such as learning and memory. This remodeling occurs at multiple levels: synaptic strength, receptor composition, and dendritic architecture. While neuroplasticity is essential for adaptive learning, it can also enable mal-adaptations such as addiction or chronic pain. We recently identified Organic Anion Transporter 1 (OAT1) as a modulator in the transition from acute to chronic pain. Our preliminary work supports the hypothesis that OAT1 is expressed in the hippocampus where it influences adaptive processes by modulating synaptic protein composition and signaling pathways, affecting hippocampus-dependent memory. Through a systematic multidisciplinary approach, we propose to first characterize metabolites transported by OAT1 in the CNS, then examine how OAT1 modulates hippocampus-dependent behavior, followed by investigating underlying synaptic signaling mechanisms and structural plasticity changes. Using complementary techniques including metabolomics, behavioral testing, electrophysiological recordings, and structural analyses in both in vitro and in vivo models, we aim to establish a comprehensive understanding of OAT1's role in hippocampal plasticity. This research could reveal novel mechanisms underlying adaptive and maladaptive plasticity with potential implications for neurological and cognitive disorders.

• DFG Programme: Research Grants
• Co-Investigators: Professor Dr. Andreas Draguhn; Professorin Dr. Ana M. M. Oliveira