FUNCTIONAL DIVERSITY OF MATURE DENTATE GYRUS GRANULE CELLS ALONG THE RADIAL AXIS

The dentate gyrus is the main entry gate to the hippocampus and plays fundamental roles in memory acquisition, recall, and pattern discrimination. Mature granule cells (GCs), the principal neurons of the dentate gyrus, have long been regarded as a functionally uniform population that, due to their hyperpolarized resting membrane potential and low excitability, supports pattern separation. Here, we challenge this view and show that mature GCs form a heterogeneous population across the radial axis of the GC layer, exhibiting distinct intrinsic, synaptic, morphological, and functional properties. Using simultaneous whole-cell patch-clamp recordings in acute hippocampal slices from mice, we compared GCs located near the molecular layer (outer GCs; OGCs) with those closer to the hilus (inner GCs; IGCs). OGCs exhibited lower input resistance and higher membrane capacitance, consistent with reduced intrinsic excitability and a larger membrane surface area compared with IGCs. Moreover, OGCs showed a higher rheobase, wider firing dynamic range, and higher maximal firing frequencies. In addition, OGCs received stronger and more numerous excitatory and inhibitory synaptic inputs, indicating enhanced drive from the entorhinal cortex and tighter inhibitory control, although excitation–inhibition ratio was constant across depth. Morphologically, OGCs displayed broader and more complex dendritic arborizations than IGCs, supporting their distinct electrophysiological profiles. Finally, multiplane in vivo two-photon imaging in head-fixed mice performing a virtual reality navigation task revealed that OGCs exhibit higher activity levels and distinct spatial properties during spatial behavior. Together, these findings reveal a depth-dependent functional organization of mature dentate gyrus GCs with implications for hippocampal computation.