Hippocampus and Memory: Neuroanatomy and Clinical Disorders
Hacı Mert Gökhan
@hacimertgokhan
Overview
The hippocampus is a curved structure in the medial temporal lobe, named for its resemblance to a seahorse (Greek: hippos = horse, kampos = sea monster). It is critical for consolidating new declarative memories — facts (semantic) and events (episodic) — and spatial navigation.
Anatomical Location and Composition
Located in the floor of the inferior horn of the lateral ventricle, the hippocampal formation consists of:
- Hippocampus proper (Ammon's horn, cornu ammonis)
- Dentate gyrus
- Subiculum
- Entorhinal cortex (the major gateway from neocortex)
Cytoarchitecture: Cornu Ammonis Layers
The hippocampus has a characteristic layered structure:
- CA1: Most vulnerable to ischemia (Sommer sector). First region damaged in global hypoxia.
- CA2: Relatively ischemia-resistant.
- CA3: Receives mossy fiber input from dentate granule cells.
- CA4: Within the hilus of the dentate gyrus.
The Trisynaptic Circuit
Information flow through the hippocampus follows a classic three-step pathway:
- Perforant path: Entorhinal cortex → dentate gyrus granule cells
- Mossy fiber pathway: Dentate granule cells → CA3 pyramidal cells
- Schaffer collateral pathway: CA3 → CA1 pyramidal cells → subiculum → back to entorhinal cortex
This unidirectional loop is the anatomical basis for memory encoding and retrieval.
Long-Term Potentiation (LTP)
The cellular mechanism of memory: high-frequency stimulation of CA3 axons strengthens synaptic transmission at Schaffer collateral-CA1 synapses for hours to days. NMDA receptor activation (with co-incident glutamate + postsynaptic depolarization) allows Ca²⁺ influx, triggering AMPA receptor insertion and structural synaptic changes.
Clinical Correlations
Alzheimer's Disease
- Earliest and most severe neurodegeneration occurs in the entorhinal cortex and CA1
- Results in anterograde amnesia (inability to form new memories) — patients cannot remember what they ate for breakfast
- Neurofibrillary tangles (hyperphosphorylated tau) and accumulate