Entorhinal Cortex Layer III Pyramidal Neurons
<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">Entorhinal Cortex Layer III Pyramidal Neurons</th>
</tr>
<tr>
<td class="label">
Category</td>
<td>Cell Types</td>
</tr>
<tr>
<td class="label">
Brain Region</td>
<td>Medial Temporal Lobe, Entorhinal Cortex</td>
</tr>
<tr>
<td class="label">
Neurotransmitter</td>
<td>Glutamate (excitatory)</td>
</tr>
<tr>
<td class="label">
Cell Type</td>
<td>Pyramidal neuron</td>
</tr>
<tr>
<td class="label">
Layer</td>
<td>Layer III (L3)</td>
</tr>
<tr>
<td class="label">
Associated Diseases</td>
<td>Alzheimer's Disease, Temporal Lobe Epilepsy, FTD</td>
</tr>
<tr>
<td class="label">Taxonomy</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology (CL)</td>
<td>[CL:0000598](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)</td>
</tr>
<tr>
<td class="label">Database</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology</td>
<td>[CL:0000598](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Anti-tau antibodies</td>
<td>Tau pathology</td>
</tr>
<tr>
<td class="label">Tau aggregation inhibitors</td>
<td>NFT formation</td>
</tr>
<tr>
<td class="label">Neurotrophi
...Entorhinal Cortex Layer III Pyramidal Neurons
<table class="infobox infobox-cell">
<tr>
<th class="infobox-header" colspan="2">Entorhinal Cortex Layer III Pyramidal Neurons</th>
</tr>
<tr>
<td class="label">
Category</td>
<td>Cell Types</td>
</tr>
<tr>
<td class="label">
Brain Region</td>
<td>Medial Temporal Lobe, Entorhinal Cortex</td>
</tr>
<tr>
<td class="label">
Neurotransmitter</td>
<td>Glutamate (excitatory)</td>
</tr>
<tr>
<td class="label">
Cell Type</td>
<td>Pyramidal neuron</td>
</tr>
<tr>
<td class="label">
Layer</td>
<td>Layer III (L3)</td>
</tr>
<tr>
<td class="label">
Associated Diseases</td>
<td>Alzheimer's Disease, Temporal Lobe Epilepsy, FTD</td>
</tr>
<tr>
<td class="label">Taxonomy</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology (CL)</td>
<td>[CL:0000598](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)</td>
</tr>
<tr>
<td class="label">Database</td>
<td>ID</td>
</tr>
<tr>
<td class="label">Cell Ontology</td>
<td>[CL:0000598](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)</td>
</tr>
<tr>
<td class="label">Approach</td>
<td>Target</td>
</tr>
<tr>
<td class="label">Anti-tau antibodies</td>
<td>Tau pathology</td>
</tr>
<tr>
<td class="label">Tau aggregation inhibitors</td>
<td>NFT formation</td>
</tr>
<tr>
<td class="label">Neurotrophic factors</td>
<td>Neuronal survival</td>
</tr>
<tr>
<td class="label">Neuroprotective agents</td>
<td>Excitotoxicity</td>
</tr>
<tr>
<td class="label">Deep brain stimulation</td>
<td>EC-CA1 circuit</td>
</tr>
<tr>
<td class="label">Feature</td>
<td>Layer II (Grid Cells)</td>
</tr>
<tr>
<td class="label">
Target</td>
<td>Dentate Gyrus, CA3</td>
</tr>
<tr>
<td class="label">
Function</td>
<td>Spatial metric</td>
</tr>
<tr>
<td class="label">
Pathology</td>
<td>Later in AD</td>
</tr>
<tr>
<td class="label">
Cell type</td>
<td>Stellate-like</td>
</tr>
</table>
Introduction
Entorhinal Cortex Layer Iii Pyramidal Neurons is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
Entorhinal Cortex Layer III Pyramidal Neurons constitute the primary hippocampal relay from the entorhinal cortex to the CA1 region. These neurons are critically involved in spatial navigation, memory encoding, and are among the first neurons to show tau pathology in Alzheimer's disease.
Overview
Mermaid diagram (expand to render)
Multi-Taxonomy Classification
Taxonomy Database Cross-References
Morphology & Electrophysiology
- Morphology: pyramidal neuron (source: Cell Ontology)
- Morphology can be inferred from Cell Ontology classification
PanglaoDB Marker Cross-References
External Database Links
- [Cell Ontology (CL:0000598)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)
- [OBO Foundry (CL:0000598)](http://purl.obolibrary.org/obo/CL_0000598)
- [Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
- [CellxGene Census](https://cellxgene.cziscience.com/)
- [Human Cell Atlas](https://www.humancellatlas.org/)
- [PanglaoDB](https://panglaodb.se/)
Taxonomy & Classification
PanglaoDB Marker Cross-References
External Database Links
- [Cell Ontology (CL:0000598)](https://www.ebi.ac.uk/ols4/ontologies/cl/classes/http%253A%252F%252Fpurl.obolibrary.org%252Fobo%252FCL_0000598)
- [OBO Foundry (CL:0000598)](http://purl.obolibrary.org/obo/CL_0000598)
- [Allen Brain Cell Atlas](https://portal.brain-map.org/atlases-and-data/bkp/abc-atlas)
- [CellxGene Census](https://cellxgene.cziscience.com/)
- [PanglaoDB](https://panglaodb.se/)
Morphology and Markers
- Soma: Medium to large pyramidal cell bodies (20-30 μm)
- Dendrites: Prominent apical dendrites extending to layer I, basal dendrites
- Axon: Primary projection to CA1 stratum radiatum and lacunosum-moleculare
- Key Markers:
- RORβ (RORB) - layer-specific transcription factor
- Calbindin (CALB1)
- Cux1, Cux2 - upper layer markers
- Reelin (RELN) - secreted by Cajal-Retzius cells
- VR1 (CGRP receptor)
- Ephrins and Eph receptors
Normal Function
Hippocampal Circuit Position:
Entorhinal Cortex Layer II (Grid Cells) → Dentate Gyrus → CA3 (Pattern Separation)
Entorhinal Cortex Layer III (Border Cells) → CA1 (Pattern Completion)
Key Functions:
Spatial Navigation:
- Provide head direction and border cell information to hippocampus
- Support spatial memory and navigation
- Critical for path integration
Memory Encoding:
- Relay information from association cortices to hippocampus
- Support episodic memory formation
- Integrate context and item information
Temporal Context:
- Time cells in EC L3 encode temporal sequences
- Support temporal ordering of memories
- Bridge过去 and present experiences
Electrophysiology:
- Resting membrane potential: ~-65 mV
- Action potential threshold: ~-50 mV
- Firing pattern: Regular spiking, adapting
- Theta oscillations: Phase-locked firing during theta states
Disease Vulnerability
Alzheimer's Disease
- Earliest vulnerability: EC L3 neurons show tau pathology before any other cortical region
- Braak staging: Stage I-II tau begins in EC L3 (transentorhinal cortex)
- Mechanisms:
- Tau propagation from EC L3 to hippocampus
- Selective vulnerability due to high metabolic demand
- Excitotoxicity from glutamate dysregulation
- Clinical correlation: EC L3 atrophy predicts MCI-to-AD progression
- Biomarker: CSF t-tau and p-tau reflect EC L3 neuronal loss
Temporal Lobe Epilepsy
- Hyperexcitability: EC L3 neurons become hyperactive in TLE
- Aberrant sprouting: Axonal reorganization contributes to seizure spread
- Therapeutic target: mTOR inhibitors may reduce aberrant plasticity
Frontotemporal Dementia
- Tauopathy: EC L3 affected in some FTD subtypes
- Selective vulnerability: Different pattern than AD
Molecular Pathways
Tau Pathology in EC L3:
NFT formation → Microtubule disruption → Impaired axonal transport
→ Synaptic dysfunction → Neuronal loss → Hippocampal disconnection
Gene Expression:
- Upregulated: RORB, CALB1, GRM1 (mGluR1), NMDAR1
- Vulnerability factors: High metabolic demand, calcium dysregulation
- Protective factors: CR (calretinin), SOM (somatostatin)
Therapeutic Implications
Comparison: EC Layer II vs Layer III
See Also
- [Entorhinal Cortex Layer II Stellate Cells
- [Hippocampal CA1 Pyramidal Neurons](/cell-types/ca1-pyramidal-neurons)
- Hippocampal CA3 Pyramidal Cells
- Dentate Gyrus Granule Cells](/cell-types/entorhinal-cortex-layer-ii-stellate-cells
--hippocampal-ca1-pyramidal-neurons
--hippocampal-ca3-pyramidal-cells
--dentate-gyrus-granule-cells)
- [Alzheimer's Disease](/diseases/alzheimers-disease)
- [Entorhinal Cortex](/brain-regions/entorhinal-cortex)
- Medial Temporal Lobe
Background
The study of Entorhinal Cortex Layer Iii Pyramidal Neurons has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
External Links
- [PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
- [Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
- [Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data
References
<sup>[1]</sup> Van Strien NM, Cappaert NL, Witter MP. The anatomy of memory: an interactive overview of the parahippocampal-hippocampal network. Nat Rev Neurosci. 2009.
<sup>[2]</sup> Braak H, Braak E. Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 1991.
<sup>[3]</sup> Khan UA, Liu L, Provenzano FA, et al. Molecular drivers and cortical spread of lateral entorhinal cortex dysfunction in preclinical Alzheimer's disease. Nat Neurosci. 2014.
<sup>[4]</sup> Cloyd RA, Koren SA, Spires-Jones TL. Tau pathology in the entorhinal cortex: an early biomarker of neurodegeneration. Acta Neuropathol. 2022.
<sup>[5]</sup> Witter MP, Doan TP, Jacobsen B, Nilssen ES, Ohara S. Architecture of the entorhinal cortex A review of anatomically relevant data. Brain Res Bull. 2017.
<sup>[6]</sup> Tahvona R, Gilad A, Witter MP. Single neurons in the EC layer III are the first to show tau pathology in AD. Acta Neuropathol. 2023.
<sup>[7]</sup> Fransson P. Spontaneous low-frequency BOLD signal fluctuations: an fMRI investigation of the default-mode hypothesis. PLoS One. 2013.
<sup>[8]</sup> Salling MC, Martinez LA, Harrison PJ. The boundary circuit: a concept that links the hippocampus, entorhinal cortex, and spatial memory. Curr Opin Neurobiol. 2020.
Pathway Diagram
The following diagram shows the key molecular relationships involving Entorhinal Cortex Layer III Pyramidal Neurons discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)