Long-Term Potentiation (LTP)

Definition and Mechanism

Long-Term Potentiation (LTP) is a persistent strengthening of synapses—the connections between neurons—that occurs after brief, high-frequency stimulation. LTP is considered a fundamental mechanism for learning and memory, as it increases the efficiency of communication between neurons.

• Key Term: Synapse – the junction between two neurons where communication occurs.

• Key Term: AMPA receptors – a type of glutamate receptor involved in fast synaptic transmission in the central nervous system.

How LTP is Induced

• High-Frequency Stimulation: LTP typically begins with brief, high-intensity stimulation of a neuron, causing a large release of neurotransmitters (e.g., glutamate).

• Calcium Influx: Neurotransmitter binding to postsynaptic receptors, especially NMDA receptors, leads to an influx of calcium ions (Ca2+) into the postsynaptic cell.

• Cellular Cascades: The increased calcium activates various signaling pathways and protein kinases, such as CAMK2 and protein kinase C.

• Synaptic Changes: These kinases strengthen the synapse by:

  • Inserting more AMPA receptors into the postsynaptic membrane, increasing sensitivity to glutamate.

  • Phosphorylating existing AMPA receptors, making them more efficient at transporting ions.

Example: LTP is critical for memory formation in the hippocampus.

Drug Effects on Synaptic Transmission

Overview

Drugs can alter synaptic transmission by interfering with the communication between neurons at various stages. They may increase or decrease the normal activity of neurotransmitters through several mechanisms.

Mimicking Neurotransmitters (Agonists)

• Definition: Agonists are drugs that mimic the action of naturally occurring neurotransmitters by binding to and activating receptors on the postsynaptic neuron.

• Example: Morphine mimics endorphins, binding to opioid receptors to produce pain relief.

Blocking Neurotransmitter Receptors (Antagonists)

• Definition: Antagonists bind to receptors but do not activate them, blocking the natural neurotransmitter from binding and thus suppressing neural signaling.

• Example: Scopolamine blocks acetylcholine receptors, helping prevent motion sickness.

Stimulating or Inhibiting Neurotransmitter Release

• Increase: Some drugs force neurons to release larger amounts of neurotransmitters (e.g., methamphetamine increases dopamine release).

• Decrease: Other drugs block the packaging of neurotransmitters into vesicles, reducing release (e.g., reserpine blocks monoamine neurotransmitter storage).

Interfering with Neurotransmitter Reuptake

• Definition: After neurotransmitter release, reuptake proteins recycle them back into the presynaptic neuron. Drugs can block these transporters, increasing neurotransmitter levels in the synapse.

• Example: Cocaine blocks the reuptake of dopamine, serotonin, and norepinephrine. SSRIs block serotonin reuptake, increasing its synaptic concentration.

Affecting Enzyme Breakdown

• Definition: Some drugs inhibit enzymes that degrade neurotransmitters, prolonging their action.

• Example: Monoamine oxidase inhibitors (MAOIs) prevent the breakdown of serotonin, dopamine, and norepinephrine.

Blocking Neurotransmitter Synthesis

• Definition: Some drugs block the enzymes needed to synthesize neurotransmitters, reducing their supply.

• Example: Alpha-methyltyrosine inhibits tyrosine hydroxylase, reducing catecholamine synthesis.

Action Potentials: Cellular Events

Overview

An action potential is a rapid, temporary change in a cell's membrane potential, allowing neurons to transmit electrical signals over long distances. The process involves a sequence of ion channel openings and closings.

Phases of the Action Potential

1. Resting Potential: The neuron maintains a stable, negative membrane potential (about -70 mV) due to the distribution of sodium (Na+) and potassium (K+) ions.

2. Depolarization to Threshold: A stimulus causes some Na+ channels to open, making the inside of the cell less negative. If the threshold (about -55 mV) is reached, more Na+ channels open.

3. Rapid Sodium Influx: Voltage-gated Na+ channels open, causing a rapid influx of Na+ ions and a sharp rise in membrane potential.

4. Peak and Repolarization: At the peak (about +30 mV), Na+ channels inactivate and voltage-gated K+ channels open, allowing K+ to exit the cell, repolarizing the membrane.

5. Hyperpolarization: K+ channels may remain open slightly longer, causing the membrane potential to become more negative than the resting potential.

6. Return to Resting Potential: The sodium-potassium pump restores the original ion distribution, returning the membrane to its resting state.

Key Terms and Concepts

• Threshold: The critical level of depolarization required to trigger an action potential.

• All-or-None Principle: Once threshold is reached, an action potential is generated and propagated without decrement.

• Refractory Period: A period during which the neuron is less responsive to further stimulation, ensuring one-way propagation of the action potential.

Relevant Equation

The Nernst equation can be used to calculate the equilibrium potential for a particular ion:

Where:

• Eion = equilibrium potential for the ion

• R = universal gas constant

• T = temperature in Kelvin

• z = charge of the ion

• F = Faraday's constant

• [ion]outside and [ion]inside = ion concentrations outside and inside the cell

Summary Table: Drug Effects on Synaptic Transmission