Electrophysiological and molecular characterization of the parasubiculum

The parahippocampal region is thought to be critical for memory and spatial navigation. Within this region lies the parasubiculum, a small structure that exhibits strong theta modulation, contains functionally specialised cells and projects to layer II of the medial entorhinal cortex (MEC). Thus, it is uniquely positioned to influence firing of spatially modulated cells in the MEC and play a key role in the internal representation of the external environment. However, the basic neuronal composition of the parasubiculum remains largely unknown, and its border with the MEC is often ambiguous. We combine electrophysiology and immunohistochemistry in adult mice (both sexes) to define first, the boundaries of the parasubiculum, and second, the major cell types found in this region. We find distinct differences in the colabelling of molecular markers between the parasubiculum and the MEC, allowing us to clearly separate the two structures. Moreover, we find distinct distribution patterns of different molecular markers within the PaS, across both superficial-deep and dorsal-ventral axes. Using unsupervised cluster analysis, we find that neurons in the parasubiculum can be broadly separated into three clusters based on their electrophysiological properties, and that each cluster corresponds to a different molecular marker. We demonstrate that while the PaS aligns structurally to some to general cortical principals, it also shows divergent features in particular in contrast to the MEC. This work will form an important basis for future studies working to disentangle the circuitry underlying memory and spatial navigation functions of the parasubiculum.We identify the major neuron types in the parasubiculum using immunohistochemistry and electrophysiology, and determine their distribution throughout the PaS. We find that the neuronal composition of the parasubiculum differs considerably in comparison to the neighbouring medial entorhinal cortex. Both regions are involved in spatial navigation. Thus, our findings are of importance for unravelling the underlying circuitry of this process and for determining the role of the parasubiculum within this network