Morpho-electric diversity of human hippocampal CA1 pyramidal neurons

Mertens, Eline J.; Leibner, Yoni; Pie, Jean; Galakhova, Anna A.; Waleboer, Femke; Meijer, Julia; Heistek, Tim S.; Wilbers, René; Heyer, Djai; Goriounova, Natalia A.; Idema, Sander; Verhoog, Matthijs B.; Kalmbach, Brian E.; Lee, Brian R.; Gwinn, Ryder P.; Lein, Ed S.; Aronica, Eleonora; Ting, Jonathan; Mansvelder, Huibert D.; Segev, Idan; de Kock, Christiaan P.J.

doi:10.1016/j.celrep.2024.114100

Cited by 6 publications

(1 citation statement)

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“…Yet how cells and circuits generate these incredible phenomena remains unknown. In particular, we do not know whether the human brain is simply a scaled version of the extensively studied rodent brain (DeFelipe, 2011; Herculano-Houzel et al, 2015), or whether its uniqueness is produced by the specific properties of cells (Eyal et al, 2016), dendrites (Gidon et al, 2020; Mertens et al, 2024), or synapses (Campagnola et al, 2022; Molnár et al, 2016, 2008; Testa-Silva et al, 2014). Distinguishing between these possibilities requires structural and functional analysis of living human brain tissue.…”

Section: Introductionmentioning

confidence: 99%

Human hippocampal CA3 uses specific functional connectivity rules for efficient associative memory

Watson,

Vargas-Barroso,

Morse-Mora

et al. 2024

Preprint

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The human brain has remarkable computational power. It generates sophisticated behavioral sequences, stores engrams over an individual's lifetime, and produces higher cognitive functions up to the level of consciousness. However, so little of our neuroscience knowledge covers the human brain, and it remains unknown whether this organ is truly unique, or is a scaled version of the extensively studied rodent brain. To address this fundamental question, we determined the cellular, synaptic, and connectivity rules of the hippocampal CA3 recurrent circuit using multicellular patch clamp-recording. This circuit is the largest autoassociative network in the brain, and plays a key role in memory and higher-order computations such as pattern separation and pattern completion. We demonstrate that human hippocampal CA3 employs sparse connectivity, in stark contrast to neocortical recurrent networks. Connectivity sparsifies from rodents to humans, providing a circuit architecture that maximizes associational power. Unitary synaptic events at human CA3–CA3 synapses showed both distinct species-specific and circuit-dependent properties, with high reliability, unique amplitude precision, and long integration times. We also identify differential scaling rules between hippocampal pathways from rodents to humans, with a moderate increase in the convergence of CA3 inputs per cell, but a marked increase in human mossy fiber innervation. Anatomically guided full-scale modeling suggests that the human brain's sparse connectivity, expanded neuronal number, and reliable synaptic signaling combine to enhance the associative memory storage capacity of CA3. Together, our results reveal unique rules of connectivity and synaptic signaling in the human hippocampus, demonstrating the absolute necessity of human brain research and beginning to unravel the remarkable performance of our autoassociative memory circuits.

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