Resilience within the aging hippocampus: electrophysiological insights into the excitability of distinct neuronal populations

The hippocampus is one of the most plastic and functionally integrated structures of the mammalian brain, playing a fundamental role in learning, memory, and emotional regulation. With aging, the finely tuned mechanisms that govern hippocampal function may undergo physiological decline that can, in turn, influence network dynamics and cognitive performance. Understanding how neuronal excitability and circuit integrity are maintained, or modified, during aging is essential to elucidate the mechanisms that may support hippocampal resilience across the lifespan. Here, we performed whole-cell patch-clamp recordings from granule cells of the dentate gyrus (DGGCs), pyramidal neurons of the subiculum (Sub Pyr), and neurogliaform cells (NGFCs) of the stratum lacunosum-moleculare of the ventral hippocampus from adult (3–4 months), middle-aged (12–14 months), or old (24–26 months) mice. Intrinsic membrane properties, neuronal evoked excitability, firing behaviour, action potential dynamics, and responsiveness to physiologically relevant stimulation patterns were systematically compared across ages to assess whether neuronal excitability within the ventral hippocampus is preserved or gradually reshaped during aging. Our results revealed that aging induces biophysical adjustments, such as hyperpolarization of the resting membrane potential of Sub Pyr and NGFCs, and an increase in membrane capacitance only in Sub Pyr. However, the overall excitability of both excitatory and inhibitory neurons remain largely preserved. Moreover, DGGCs did not exhibit age-dependent alterations, possibly reflecting the fundamental contribution of adult hippocampal neurogenesis, which helps stabilize the proper functioning of the dentate network. Taken together, these findings highlight the subfield-specific nature of age-related hippocampal adaptation and show that both excitatory and inhibitory components of the ventral hippocampal circuitry maintain their fundamental electrophysiological identity from adulthood into senescence.