On the origin of memory neurons in the human hippocampus

Trends Cogn Sci. 2025 May;29(5):421-433. doi: 10.1016/j.tics.2025.01.013. Epub 2025 Mar 4.

Abstract

The hippocampus is essential for episodic memory, yet its coding mechanism remains debated. In humans, two main theories have been proposed: one suggests that concept neurons represent specific elements of an episode, while another posits a conjunctive code, where index neurons code the entire episode. Here, we integrate new findings of index neurons in humans and other animals with the concept-specific memory framework, proposing that concept neurons evolve from index neurons through overlapping memories. This process is supported by engram literature, which posits that neurons are allocated to a memory trace based on excitability and that reactivation induces excitability. By integrating these insights, we connect two historically disparate fields of neuroscience: engram research and human single neuron episodic memory research.

Keywords: Indexing Theory; concept neurons; conjunctive coding; engram; episodic memory; hippocampus; memory trace; single neurons.

Publication types

  • Review

MeSH terms

  • Animals
  • Hippocampus* / cytology
  • Hippocampus* / physiology
  • Humans
  • Memory* / physiology
  • Memory, Episodic*
  • Neurons* / physiology