Physiological landmarks reveal the laminar organization of the primate hippocampus

Abstract

The laminar anatomy of the hippocampal microcircuit is conserved across mammals, and its physiology has been characterized extensively in rodents, yet how this circuitry is organized physiologically in the primate brain remains poorly understood. Here we used high-density Neuropixels probes to record simultaneously across the subfields of CA1, CA3 and the dentate gyrus in two awake macaques. Sharp-wave ripples and dentate spikes produced current source density signatures that provided physiological landmarks for CA1 and the dentate gyrus, enabling alignment of recordings to hippocampal cytoarchitecture. Theta-band (3-7 Hz) oscillatory activity occurred in discrete bouts whose prevalence peaked in the stratum lacunosum-moleculare. In CA1, gamma-band amplitude was modulated by theta-band phase, with fast and slow gamma preferentially coupled to distinct phases of the theta cycle. Putative principal cells and two interneuron classes differed systematically in firing rate, burstiness, and rhythmic modulation, with principal cells showing theta-rhythmic firing and wide-waveform interneurons showing alpha- and beta-rhythmic firing. Cross-correlogram analyses revealed sparse, distance-dependent functional coupling with a consistent directional hierarchy in which principal cells led interneurons. Together, these results identify the laminar microcircuit organization of the primate hippocampus in vivo and provide a new physiological framework for interpreting primate hippocampal recordings.