Does a Stronger Synapse Become a Memory?

Jul 27

3 min read

What long-term potentiation can, and cannot, tell us about learning

A discovery that transformed memory research

Long-term potentiation was first described in detail in 1973 by neuroscientists Timothy Bliss and Terje Lømo. While stimulating a pathway leading into the hippocampus of rabbits, they observed that repeated electrical activity produced a stronger response that continued after the stimulation had ended. The discovery offered a compelling possibility: perhaps experience could leave a lasting trace by changing the strength of connections between neurons.

How does a synapse become stronger?

In a widely studied form of hippocampal LTP, the neurotransmitter glutamate activates receptors on the postsynaptic neuron. Strong or coordinated activity allows calcium to enter the cell through NMDA receptors, triggering molecular changes that increase the number or effectiveness of AMPA receptors at the synapse. The next time the presynaptic neuron releases glutamate, the postsynaptic response may therefore be stronger. If the change continues, protein synthesis and structural modifications can help stabilise it.

Why LTP looked like a memory mechanism

LTP has several properties that make it well suited to learning. It can persist over time, affect specific active connections and strengthen synapses when neurons are activated together. Experiments have also shown that learning can induce LTP-like changes in the hippocampus, while disrupting particular forms of synaptic plasticity can interfere with memory. This evidence supports a meaningful connection between LTP and learning, but it does not prove that every memory is stored as one strengthened synapse.

Strengthening can reshape the synapse

LTP is not limited to a change in electrical responsiveness. It can also be accompanied by physical changes in dendritic spines, the small projections that receive many excitatory signals. Some spines enlarge, become more stable or reorganise their internal molecular structure after plasticity is induced. Research has found that LTP can increase a synapse’s probability of survival, suggesting that neural activity can influence both the strength and the long-term stability of a connection.

Why memory needs more than LTP

The brain cannot simply strengthen every active connection indefinitely. Learning also involves weakening synapses through long-term depression, adjusting neuronal excitability, controlling inhibition and maintaining balance across entire networks. Different forms of plasticity operate over different time scales, and some do not follow the classic rule that presynaptic and postsynaptic neurons must fire almost simultaneously. Memory therefore depends on a collection of interacting biological processes rather than one universal mechanism.

From individual synapses to memory engrams

Modern research increasingly studies memories through engrams: populations of cells that are modified during learning and later reactivated during recall. Synaptic strengthening may help organise the connections within these populations, but the memory is distributed across a circuit rather than contained inside a single synapse. A 2025 study examining a memory engram in mice found selective changes in synaptic connectivity associated with learning, illustrating how researchers are beginning to connect molecular plasticity with the architecture of entire memory networks.

Conclusions

Long-term potentiation gave neuroscience a biological explanation for how brief activity might produce lasting change. It showed that synapses are not fixed points of communication: their strength, structure and stability can be shaped by experience.

Yet LTP should not be understood as the memory itself. Remembering requires coordinated changes across many synapses and neurons, supported by processes that strengthen some connections, weaken others and reorganise activity throughout wider networks.

A stronger synapse may form part of a memory’s physical trace.

The memory, however, belongs to the circuit.

Source:

Bliss, T. V. P., & Lømo, T. (1973). Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path.

Abraham, W. C. et al. (2024). Long-term potentiation: 50 years on: past, present and future.

Caya-Bissonnette, L. et al. (2024). Half a century legacy of long-term potentiation.

Hagena, H., et al. (2024). Interplay of hippocampal long-term potentiation and long-term depression in learning and memory.