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Inhibitory Neurons in Human Anterior Entorhinal Cortex and Some Comparisons With the Rhesus Monkey
Julied Bautista1, Vijaya Verma1, Helen Barbas1,2,3,4
1Department of Health Sciences, Neural Systems Laboratory, Boston University, Boston, Massachusetts, USA.
The Journal of Comparative Neurology
|June 30, 2026
Summary
The anterior entorhinal cortex (EC) has distinct inhibitory neuron populations, identified by calretinin (CR), calbindin (CB), and parvalbumin (PV), with varying distributions and GABAergic marker expression in humans and monkeys. These differences suggest specialized microenvironments influencing hippocampal memory processing.
Area of Science:
- Neuroscience
- Neuroanatomy
- Cellular Neuroscience
Background:
- The primate anterior entorhinal cortex (EC) is crucial for memory, receiving input from emotional and association areas.
- Inhibitory neurons expressing calcium-binding proteins (CBPs) like calretinin (CR), calbindin (CB), and parvalbumin (PV) modulate EC processing.
- Understanding the distribution and neurochemical properties of these inhibitory neurons is key to deciphering EC function.
Purpose of the Study:
- To compare the neurochemical classes of inhibitory neurons in the anterior EC of humans and rhesus monkeys.
- To investigate the laminar and regional distribution of CR, CB, and PV neurons in the anterior EC.
- To determine the colocalization of these CBPs with the GABAergic marker GAD67/GAD1 in the human anterior EC.
Main Methods:
- Stereological analysis of inhibitory neuron populations in the anterior EC of humans and rhesus monkeys.
- Immunohistochemical identification of neurons expressing CR, CB, PV, and GAD67/GAD1.
- Quantitative assessment of neuronal densities, laminar distribution, regional differences, and marker colocalization.
Main Results:
- CR neurons were the most prevalent inhibitory subpopulation, followed by CB and then PV, in both species.
- CR neurons were concentrated in superficial layers (I-II), CB in intermediate layers (II-III), and PV in deeper layers.
- Human anterior EC showed regional variations in CBP-positive neuron densities and differential colocalization with GAD67/GAD1, with PV neurons being predominantly GABAergic.
Conclusions:
- The anterior EC exhibits distinct inhibitory microenvironments in its medial and lateral sectors.
- The observed patterns of inhibitory neuron distribution and neurochemistry are conserved between humans and rhesus monkeys.
- These specialized inhibitory circuits likely play a significant role in modulating hippocampal input and output for memory formation and retrieval.

