Biophysical heterogeneity and information routing in ventral CA1 circuits

Abstract

Intrinsic biophysical diversity is a defining feature of neuronal populations, yet how this heterogeneity relates to projection identity and information encoding remains unclear. Pyramidal neurons of the ventral CA1 (vCA1) hippocampus exhibit substantial variability in intrinsic membrane properties and project to multiple downstream targets, including the amygdala, prefrontal cortex, nucleus accumbens, and main olfactory bulb (MOB). Although projection-defined populations have been identified how this constrains their biophysics, and in turn how they shape stimulus encoding at the single-cell and population levels is not well understood. To address this question, I analyzed whole-cell recording data obtained from projection- defined vCA1 neurons, comparing olfactory bulb (OB)-projecting neurons with an unlabeled population representing mixed projection targets. Passive membrane properties confirmed substantial intrinsic heterogeneity within both groups. I then quantified stimulus encoding by computing mutual information between controlled fluctuating input currents (varying in gain, variance, event frequency, and correlation structure) and spike responses. Despite pronounced variability in spike timing and trial-to-trial reliability, single-cell mutual information was comparable between OB-projecting and non-OB-projecting neurons across stimulus conditions. In contrast, population-level analyses revealed stimulus-dependent differences in encoding capacity. OB-projecting populations exhibited higher mutual information under gain- and variance-modulated inputs and at high event frequencies, whereas non-OB populations encoded more information under low-event, high-correlation conditions. OB-projecting neurons also demonstrated consistently higher information per spike, indicating greater encoding efficiency. In both populations, mutual information increased monotonically with population size. These findings demonstrate that projection-defined vCA1 neurons can exhibit similar single- cell encoding capacity while significantly differing in population-level information processing in a stimulus-dependent manner. This work provides a quantitative framework linking intrinsic heterogeneity, projection identity, and population coding in hippocampal–sensory feedback circuits.