Long-Term Potentiation (LTP)

Cells that fire together wire together; weak connections between neurons strengthen with repeated activation.

A persistent strengthening of synaptic connections following high-frequency stimulation; a form of synaptic plasticity.

High-frequency stimulation that induces LTP.

Changes in synaptic strength, including LTP and LTD resulting from learning or experiences.

Brain region crucial for declarative memory; part of the medial temporal lobe.

A strong stimulus at one synapse strengthens only that synapse, not others.

Weak stimulation of a synapse can be strengthened when connected to a strongly stimulated synapse.

Studying LTP outside the animal in tissue slices (often taken from the hippocampus).

Field excitatory postsynaptic potential; a measure of combined synaptic activity from many nearby neurons.

The difference in electrical charge between the inside and outside of a cell.

A change in the membrane potential, becoming less negative (more positive) inside.

A change in the membrane potential, becoming more negative inside.

LTP is measured by observing a percentage change in fEPSP strength over baseline after a strong stimulation.

NMDA receptors are crucial for LTP induction but not for its expression. They act as a "gatekeeper" allowing calcium influx only when both glutamate binds and the postsynaptic cell is sufficiently depolarized.

Calcium influx through NMDA receptors during LTP induction is essential for long-term strengthening of the synapse. Blocking calcium prevents LTP.

AMPA receptors are crucial for LTP expression. They are involved in both the pre-existing surface pool and the intracellular pool, which get mobilized to increase synaptic strength.

LTP induction requires both pre- and post-synaptic activity. Glutamate release from the presynaptic neuron is essential, but the postsynaptic neuron must also be sufficiently depolarized to remove the magnesium block from NMDA receptors.

LTP is strongly linked to Hebbian learning, the idea that "cells that fire together wire together." This suggests that LTP may be a biological mechanism underlying learning and memory.

A portion of AMPA receptors are already located on the postsynaptic membrane, providing a base level of synaptic strength. Blocking this pool hinders early stages of LTP expression.

A reserve pool of AMPA receptors is stored within the postsynaptic cell. These receptors are mobilized to the surface during LTP induction, contributing to the rapid increase in synaptic strength.

LTP results from two processes: 1) increasing the number of AMPA receptors already on the surface, and 2) recruiting additional AMPA receptors from the intracellular pool.

A measure of the strength of a group of synapses, reflecting the sum of extracellular recordings from nearby neurons.

A key requirement for LTP is the depolarization of the post-synaptic cell, activated by glutamate released from the pre-synaptic neuron.

For LTP to occur, the presynaptic neuron must release glutamate. This triggers the postsynaptic neuron to become more sensitive to glutamate, strengthening the connection between the neurons.

The postsynaptic neuron must be sufficiently depolarized, meaning its electrical charge must become more positive. This allows the NMDA receptor to open, allowing calcium ions to flow in.

Calcium ions flowing into the postsynaptic neuron through NMDA receptors are essential for triggering the molecular changes responsible for LTP.

AMPA receptors are located on the postsynaptic membrane and become more abundant during LTP. This increase in AMPA receptors makes the neuron more responsive to glutamate, strengthening the connection.

Some AMPA receptors are already present on the postsynaptic membrane before LTP. Blocking these receptors hinders the early stages of LTP expression.

A reserve pool of AMPA receptors is stored inside the postsynaptic neuron. These receptors are recruited to the membrane during LTP, contributing to the rapid increase in synaptic strength.

LTP involves two independent processes to increase synaptic strength: increasing the number of AMPA receptors already on the membrane and recruiting more AMPA receptors from the intracellular pool.

Blocking protein synthesis in the hippocampus prevents the formation of long-lasting memories, suggesting that protein synthesis is crucial for memory consolidation.

The strength of stimulation determines the type of LTP induced. Weak stimulation leads to short-lasting LTP (LTP1), while stronger stimulation leads to long-lasting LTP (LTP2 and LTP3) involving protein synthesis and gene expression.

Strong stimulation tags a synapse, marking it for future strengthening. mRNAs carrying proteins needed for LTP are then captured by the tagged synapse.

LTD is the opposite of LTP and weakens synaptic connections. It's a way to balance neuron activation and prevent over-excitation.

A mechanism where neurons adjust their excitability to maintain an optimal level of activity. Cells open chloride channels to reduce their responsiveness.

A group of neurons that represent a specific concept or memory. They are weakly connected but become strongly linked by repeated stimulation.

The medial temporal lobe (MTL) is crucial for forming new declarative memories, including facts and events. Damage to the MTL, particularly the hippocampus, impairs the ability to create new memories.

Tetanic stimulation is a high-frequency stimulation that induces long-term potentiation (LTP). Following tetanus, synapses become stronger, resulting in a more robust response to future stimuli.

LTP induction refers to the process of activating the synapse with high-frequency stimulation. LTP expression refers to the lasting changes in synaptic strength that occur after induction, leading to enhanced transmission.

The process of increasing the number of AMPA receptors (AMPARs) at the synapse, leading to stronger synaptic transmission and contributing to LTP.

Phosphorylation of Ser831 on AMPARs allows more sodium ions to enter the cell, increasing its excitability and contributing to LTP.

Phosphorylation of Ser845 tags AMPARs for removal from the synapse, reducing excitability and potentially contributing to LTD.

CaMK2, activated by calcium influx, plays a crucial role in LTP by promoting spine growth, AMPAR recruitment, and strengthening synapses.

Larger spines are more stable and tend to have more AMPARs, contributing to long-lasting LTP.

LTP is more susceptible to disruption in the first 10 minutes after induction, indicating a time window for stabilizing synaptic changes.

While LTP is initially localized to a single synapse, it can influence other synapses through various mechanisms, leading to global changes in neural networks.

Switching AMPARs from GluR1 to GluR2 removes the magnesium block, always allowing calcium ions to enter the cell, making it more sensitive to glutamate and potentially contributing to LTP.

LFS activates Ser845 phosphorylation, leading to removal of AMPARs from the membrane, reducing excitability and effectively weakening the synapse.