Olfactory and spatial coding along the proximodistal axis of hippocampal region CA1 during goal-oriented navigation

• Applicants: Professor Dr. Tobias Ackels; Dr. Oliver Barnstedt
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 563909633

The hippocampus plays a crucial role in spatial navigation and memory formation, with the CA1 subregion serving as a key site for processing diverse sensory inputs. Recent studies suggest functional differentiation along the proximodistal axis of CA1, where proximal regions are more specialized for precise spatial coding and distal regions for processing contextual and non-spatial information, such as olfactory cues. However, the dynamic roles of these regions in encoding olfactory and spatial information during active navigation remain poorly understood. This project aims to investigate how proximal and distal CA1 neurons differentially contribute to olfactory and spatial coding during goal-oriented navigation, focusing on the influence of distinct entorhinal cortex (EC) inputs. Using advanced recording techniques such as chronic dual-color calcium imaging, we will simultaneously measure the activity of proximal and distal CA1 neurons in freely moving mice during different navigation tasks. Mice will engage in two tasks: one guided by olfactory cues and the other by spatial cues. These tasks are designed to isolate distinct sensory-driven navigation strategies and allow for direct comparison of neuronal activity across CA1 regions and across tasks. By analyzing behavioral parameters such as time to goal, proximity to the reward, and error rates, we will link neuronal activity to task performance, highlighting how sensory inputs are processed in real time. To elucidate the role of medial entorhinal cortex (MEC) and lateral entorhinal cortex (LEC) projections in this differentiation, we will use optogenetic silencing to selectively inhibit these inputs during navigation tasks. This will allow us to determine how MEC and LEC influence proximal and distal CA1 activity, respectively, and how their projections contribute to encoding spatial versus olfactory information. By examining how spatial and olfactory information are distinctly processed along the proximodistal axis of CA1, we aim to uncover how hippocampal neurons create unified representations that allow animals to navigate complex environments. Overall, this work will significantly advance our understanding of hippocampal specialization, the role of cortical inputs in sensory-driven behaviors, and the neural mechanisms underlying goal-oriented navigation.

• DFG Programme: Research Grants
• Major Instrumentation: Miniature Microscope for in vivo imaging
• Instrumentation Group: 5040 Spezielle Mikroskope (außer 500-503)