Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

Cell Rep. 2024 Apr 23;43(4):114100. doi: 10.1016/j.celrep.2024.114100. Epub 2024 Apr 11.

Abstract

Hippocampal pyramidal neuron activity underlies episodic memory and spatial navigation. Although extensively studied in rodents, extremely little is known about human hippocampal pyramidal neurons, even though the human hippocampus underwent strong evolutionary reorganization and shows lower theta rhythm frequencies. To test whether biophysical properties of human Cornu Amonis subfield 1 (CA1) pyramidal neurons can explain observed rhythms, we map the morpho-electric properties of individual CA1 pyramidal neurons in human, non-pathological hippocampal slices from neurosurgery. Human CA1 pyramidal neurons have much larger dendritic trees than mouse CA1 pyramidal neurons, have a large number of oblique dendrites, and resonate at 2.9 Hz, optimally tuned to human theta frequencies. Morphological and biophysical properties suggest cellular diversity along a multidimensional gradient rather than discrete clustering. Across the population, dendritic architecture and a large number of oblique dendrites consistently boost memory capacity in human CA1 pyramidal neurons by an order of magnitude compared to mouse CA1 pyramidal neurons.

Keywords: CA1; CP: Cell biology; CP: Neuroscience; adult human hippocampus; electrophysiological features; memory capacity; morphology; pyramidal neuron; resection tissue; stratum pyramidale.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Animals
  • CA1 Region, Hippocampal* / cytology
  • CA1 Region, Hippocampal* / physiology
  • Dendrites* / physiology
  • Female
  • Humans
  • Male
  • Mice
  • Middle Aged
  • Pyramidal Cells* / physiology
  • Theta Rhythm / physiology