Characterization of spatial coding along the dorsal-ventral axis of the hippocampus using high-density neural probes
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Abstract:
The hippocampus is a critical brain region associated with spatial navigation, task learning, and memory consolidation. However, it is not a homogeneous structure; significant molecular, anatomical, and functional differences exist along its dorsal-ventral axis (M.-B. Moser and Edvard I. Moser, 1998; Fanselow and Dong, 2010; Strange, Menno P. Witter, et al., 2014). For instance, while neurons across the hippocampus encode spatial information, the dorsal and ventral subregions differ in the scale of spatial representation. These differences are attributed to distinct inputs and outputs from cortical and subcortical brain regions. Functionally, the dorsal hippocampus is primarily associated with spatial navigation, while the ventral hippocampus is linked to anxiety-related behaviors. Although hippocampal reactivation and its interaction with cortical regions are known to play a crucial role in memory consolidation, the interaction between the dorsal and ventral hippocampus in this process remains unclear. This thesis aims to investigate how neural activity in the dorsal and ventral hippocampus is coordinated or acts independently to support spatial behavioral tasks. To achieve this, eight adult male C57BL/6J mice were chronically implanted with a 4-shank Neuropixels probe (N. A. Steinmetz, C. Aydin, et al., 2021) to simultaneously record activity from the dorsal and ventral hippocampus. Our findings revealed that both the dorsal and ventral hippocampus encode spatial information with different scales. Notably, the ventral hippocampus exhibited limited participation in sharp-wave ripple activity, suggesting its minimal involvement in the spatial task. While no direct coordination of sharp-wave ripples between the two subregions was observed, a weak correlation in neural activity modulation was detected. The second part of this thesis addresses the technical challenges of using Neuropixels probes. To overcome these challenges, we developed a general approach for generating custom channel configurations without violating the hardware constraints of Neuropixels probes. This approach was implemented in an open-source Python application, NeuroCarto, which we integrated into our experimental workflow. Overall, this work establishes an experimental approach that employs 4-shank Neuropixels probes to record neural signals along the dorsal-ventral axis of the hippocampus in freely behaving mice. The application we developed significantly streamlined the creation of custom channel configurations, enhancing the efficiency of our experiments. Through this approach, we successfully recorded neural activity from the dorsal and ventral hippocampus, demonstrating their distinct roles in encoding spatial information at different scales.