Quantification of neuron types in the rodent hippocampal formation by data mining and numerical optimization

Abstract

Quantifying the population sizes of distinct neuron types in different anatomical regions is an essential step towards establishing a brain cell census. Although estimates exist for the total neuronal populations in different species, the number and definition of each specific neuron type are still intensively investigated. Hippocampome.org is an open‐source knowledge base with morphological, physiological and molecular information for 122 neuron types in the rodent hippocampal formation. While such framework identifies all known neuron types in this system, their relative abundances remain largely unknown. This work quantitatively estimates the counts of all Hippocampome.org neuron types by literature mining and numerical optimization. We report the number of neurons in each type identified by main neurotransmitter (glutamate or GABA) and axonal‐dendritic patterns throughout 26 subregions and layers of the dentate gyrus, Ammon's horn, subiculum and entorhinal cortex. We produce by sensitivity analysis reliable numerical ranges for each type and summarize the amounts across broad neuronal families defined by biomarkers expression and firing dynamics. Study of density distributions indicates that the number of dendritic‐targeting interneurons, but not of other neuronal classes, is independent of anatomical volumes. All extracted values, experimental evidence and related software code are released on Hippocampome.org.

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

“…We tested these predictions in the CA3 network. Stereology analyses indicated that CA3 contains ∼110,000 CA3 PNs per hemisphere in mouse ((Attili et al, 2022); J.F.W, unpublished), ∼300,000 CA3 PNs per hemisphere in rat (Attili et al, 2022; Boss et al, 1987), and ∼1.8 M CA3 PNs per hemisphere in humans ((González-Arnay et al, 2024; Seress, 1988; Simić et al, 1997; West, 1993; West and Gundersen, 1990) see Methods ). Therefore CA3 undergoes a massive evolutionary expansion in cell number ((Herculano-Houzel et al, 2015); see Fig.…”

A Continuous Attractor Model with Realistic Neural and Synaptic Properties Quantitatively Reproduces Grid Cell Physiology

“…Based on prior models and rodent studies, we included a cell group that provides velocity-modulated excitation to grid cells (Burak and Fiete, 2009; Solanka et al, 2015). We mapped these direction- and speed-modulated conjunctive cells to LI-II Multipolar PCs, the most abundant glutamatergic neurons in EC based on Hippocampome.org (Attili et al, 2022). These neurons have potential synaptic connections to stellate cells (Rowland et al, 2018; Tecuatl et al, 2021) and can thus supply direct excitatory input to grid cells (see Discussion for an alternative based on GABAergic signaling).…”

“…Hippocampome.org is a knowledge base of the rodent hippocampal formation circuitry and offers a wide variety of neural properties that are ready to be integrated into simulations (Wheeler et al, 2024). Parameters available from Hippocampome.org along with the corresponding experimental measurements include the Izhikevich Model (IM) of neuron firing and excitability (Komendantov et al, 2019; Venkadesh et al, 2019), Tsodyks-Markram (TM) model of synaptic signaling and short-term-plasticity (Beyeler et al, 2015; Moradi & Ascoli, 2019; Moradi et al, 2022), neuron counts (Attili et al, 2022), and connection probabilities (Tecuatl et al, 2021). Hippocampome.org also provides a wealth of neuron type-specific details about hippocampal activity and molecular expression that can add to the biological realism of computational simulations (Hamilton et al, 2017a; Hamilton et al, 2017b; Rees et al, 2016; Sanchez-Aguilera et al, 2021; White et al, 2020).…”

Formation and Retrieval of Cell Assemblies in a Biologically Realistic Spiking Neural Network Model of Area CA3 in the Mouse Hippocampus

“…This resource identifies neuron types based on their primary neurotransmitter (glutamate or GABA) and the presence of axons and dendrites across distinct layers of each cytoarchitectonic area of the HPF: entorhinal cortex, dentate gyrus, CA3, CA2, CA1, and subiculum. Hippocampome.org provides for each neuron type experimental data regarding the expression of specific molecules [26], biophysical membrane properties [27], electrophysiological firing patterns in vitro and in vivo [28,29] and population size [30,31]. Additionally, Hippocampome.org quantifies the connection probability and synaptic signals of directional pairs formed between a pre-and post-synaptic neuron type, known as potential connections, which are based on their axonal and dendritic distributions [32][33][34][35].…”