Learning and memory !
- Mechanism
- Exam priority: medium
Memories are stored by strengthening the connections between neurons; the hippocampus files facts and events.
Updated 2026-11-01
Also called: Long-term potentiation, Declarative memory
See it in 3D: Hippocampus · Fornix · Temporal lobe · Amygdala · Thalamus · Cerebellum
What it is
Memory is not one system. Declarative memory (facts and events) depends on the hippocampus and medial temporal lobe to form and consolidate it, then is stored across the cortex. Skills and habits (procedural memory) depend on the basal ganglia and cerebellum. At the synapse, learning is largely a change in strength, the best-known example being long-term potentiation through NMDA receptors.
How it works, step by step
- A strong, repeated input releases glutamate onto a hippocampal (CA1) neuron.
- AMPA receptors open and depolarize the postsynaptic membrane.
- Depolarization expels Mg²⁺ from NMDA receptors, which then let Ca²⁺ in: they act as coincidence detectors (pre- and postsynaptic activity together).
- Ca²⁺ activates kinases (CaMKII, PKC) that phosphorylate AMPA receptors and insert more of them into the membrane: early LTP.
- With repetition, signalling to the nucleus (cAMP, CREB) turns on gene expression and builds new synaptic structure: late LTP, lasting days or more.
- Over time, replay during sleep transfers the memory trace to cortical networks, making it less dependent on the hippocampus.
Memory systems and where they live
| Type | Example | Key structures |
|---|---|---|
| Episodic | What you had for breakfast | Hippocampus, medial temporal lobe, prefrontal cortex |
| Semantic | The capital of Colombia | Temporal neocortex (after hippocampal consolidation) |
| Working | Keeping a phone number in mind | Prefrontal cortex |
| Procedural | Riding a bicycle, suturing | Basal ganglia, cerebellum, motor cortex |
| Emotional conditioning | Fear of a place linked to a bad event | Amygdala |
Clinical notes
- Alzheimer disease starts in the entorhinal cortex and hippocampus: new memories fail first; acetylcholine-producing neurons of the basal forebrain are lost.
- Thiamine deficiency in alcohol use disorder or malnutrition damages the mammillary bodies and thalamus (Wernicke–Korsakoff).
- After a concussion, retrograde amnesia for the moments before the injury is typical because consolidation was interrupted.
Test yourself
Think of the answer, then tap the question to see it.
Why are NMDA receptors called coincidence detectors?
They open only when glutamate is bound and the postsynaptic membrane is already depolarized (removing the Mg²⁺ block), so they detect pre- and postsynaptic activity at the same time.
A patient with bilateral medial temporal lobe damage learns a new motor skill but does not remember practising. Why?
Procedural memory depends on basal ganglia and cerebellum, which are intact; declarative memory of the sessions needs the hippocampus.
What changes at the synapse during early versus late LTP?
Early LTP: existing AMPA receptors are phosphorylated and more are inserted. Late LTP: gene expression and protein synthesis build new synaptic structure.
Why do old memories survive in early Alzheimer disease while new ones are lost?
Disease begins in the entorhinal cortex and hippocampus, which form new memories; older consolidated memories are stored across the neocortex, which is affected later.
See it in 3D
The structures of Durgical's 3D anatomy where it happens.
Related topics
- Synaptic transmission
- The limbic system, emotion and reward
- Wakefulness, sleep, the EEG and seizures
- Basal ganglia and movement control
- Functions of the cerebellum
Related conditions
In Biochemistry
Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.
Sources: 16.2 The Mental Status Exam (OpenStax (Rice University), 2022); Neuroanatomy, Hippocampus (StatPearls (NCBI Bookshelf), 2024); Alzheimer Disease (StatPearls (NCBI Bookshelf), 2024); Neuroanatomy, Mammillary Bodies (StatPearls (NCBI Bookshelf), 2024); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 58). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).
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Representative model, for educational purposes only.