Heterogeneity of age-related neural hyperactivity along the CA3 transverse axis

Abstract

Age-related memory deficits are correlated with neural hyperactivity in the CA1 and CA3 regions of the hippocampus. Abnormal CA3 hyperactivity in aged rats has been proposed to contribute to an imbalance between the normal tradeoff between pattern separation and pattern completion, resulting in overly rigid representations. Recent evidence of functional heterogeneity along the CA3 transverse axis suggests that proximal CA3 supports pattern separation while distal CA3 supports pattern completion. It is not known whether age-related CA3 hyperactivity is uniformly represented along the CA3 transverse axis. We examined the firing rates of CA3 neurons from male young and aged Long-Evans rats along the CA3 transverse axis. Consistent with prior studies, young CA3 cells showed an increasing gradient in mean firing rate from proximal to distal CA3. However, aged CA3 cells showed an opposite trend, with a decreasing gradient from proximal to distal CA3. Thus, CA3 cells in aged rats were hyperactive in proximal CA3, but possibly hypoactive in distal CA3, compared to young rats. We suggest that, in combination with altered inputs from the entorhinal cortex and dentate gyrus, the proximal CA3 region of aged rats may switch from its normal function that reflects the pattern separation output of the DG and instead performs a computation that reflects an abnormal bias toward pattern completion. In parallel, distal CA3 of aged rats may create weaker attractor basins that promote bistable representations under certain conditions.