A topic in the Open Knowledge Graph — a free, open map of 15,290 topics and the order to learn them in.

Long-Term Depression

Graduate Depth 235 in the knowledge graph ☐ I know this ☆ Set as goal

176topics build on this

1,243prerequisites beneath it

Calcium Signaling in Neurons Glutamatergic Excitation: Information Transfer and Synaptic Plasticity +3 more→→Cerebellum: Motor Coordination and Learning Cerebellum: Motor Learning and Coordination +4 more

synaptic-plasticity learning

Core Idea

Lasting decrease from low-frequency stimulation. Moderate Ca2+ elevation activates phosphatases (calcineurin) that remove AMPA receptors, weakening transmission.

Explainer

From your understanding of postsynaptic currents and the distinction between ionotropic and metabotropic receptors, you know that synaptic transmission produces measurable electrical responses and that different receptor types trigger different intracellular signaling pathways. Long-term depression (LTD) is the complementary process to long-term potentiation (LTP) — while LTP strengthens synapses, LTD weakens them. Both are essential: a brain that could only strengthen synapses would quickly saturate, with every connection at maximum strength and no ability to discriminate signal from noise. LTD provides the erasure, refinement, and forgetting that keep neural circuits functional.

The key to understanding LTD lies in calcium concentration. Both LTP and LTD are triggered by calcium entering the postsynaptic neuron through NMDA receptors, but the *amount* of calcium determines which direction the synapse moves. High-frequency stimulation (like a burst of rapid firing) produces large, fast calcium transients that activate kinases — enzymes like CaMKII that add phosphate groups to proteins. These kinases drive AMPA receptor insertion into the postsynaptic membrane, strengthening the synapse (LTP). Low-frequency stimulation (typically around 1 Hz for several minutes) produces a modest, sustained calcium elevation that instead activates phosphatases — enzymes like calcineurin (protein phosphatase 2B) and PP1 that remove phosphate groups. These phosphatases trigger the internalization of AMPA receptors: the receptors are pulled out of the postsynaptic membrane via endocytosis and either recycled or degraded. Fewer AMPA receptors in the membrane means smaller excitatory postsynaptic currents in response to the same amount of glutamate release — the synapse has been weakened.

This calcium-threshold model — sometimes called the BCM theory after Bienenstock, Cooper, and Munro — provides an elegant explanation for bidirectional plasticity at a single synapse. The postsynaptic neuron effectively reads its own calcium signal to decide whether to strengthen or weaken: brief, intense calcium means "this connection is important, keep it," while prolonged, moderate calcium means "this connection is not contributing usefully, weaken it." The threshold between LTP and LTD is itself adjustable through metaplasticity — a synapse's recent history of activity shifts the threshold, preventing runaway potentiation or depression.

LTD is not merely a laboratory curiosity — it plays critical roles in real neural computation. In the cerebellum, LTD at parallel fiber–Purkinje cell synapses is the primary mechanism for motor learning: when a movement produces an error, climbing fiber signals trigger LTD that weakens the synaptic connections responsible for the incorrect motor command. In the hippocampus, LTD contributes to memory flexibility by allowing old associations to be overwritten with new ones. During development, LTD helps refine neural circuits by weakening inappropriate connections — for example, eliminating synapses that carry poorly correlated visual input during the critical period of visual cortex development. Without LTD, the brain would be a one-way ratchet, accumulating synaptic strength without the ability to prune, refine, or adapt.

Practice Questions 5 questions

Prerequisite Chain

Understanding Zero → The Number Zero → Counting to Five → Counting to 10 → One-to-One Correspondence → Counting a Set of Objects Up to 20 → Cardinality: The Last Number Counted → Matching Numerals to Quantities → Subitizing Small Quantities → Addition Within 10 → Making 10 as an Addition Strategy → Addition Within 20 → Doubles and Near Doubles → Doubles Facts Within 10 → Near Doubles Facts Within 20 → Mental Math Strategies for Addition → Mental Math: Adding and Subtracting Tens → Addition Within 100 → Repeated Addition as Multiplication → Multiplication as Equal Groups → Multiplication: Arrays → Basic Multiplication Facts (0s, 1s, 2s, 5s, 10s) → Multiplication Facts Within 100 → Division as Equal Sharing → Division as Grouping (Measurement Division) → Division: Grouping (Repeated Subtraction) Model → Division: Fair Sharing Model → Division as Equal Sharing → Division as Grouping → Basic Division Facts → Division Facts Within 100 → Multiplication and Division Fact Families → Relationship Between Multiplication and Division → Division Facts as Inverse of Multiplication → Remainders and Quotients in Division → Division Word Problems → Multi-Step Word Problems → Solving Multi-Step Word Problems → Multiplication Word Problems → Division Word Problems → Introduction to Long Division → Factors and Multiples → Prime and Composite Numbers → Equivalent Fractions → Relating Fractions and Decimals → Decimal Place Value → Integers and the Number Line → Comparing and Ordering Integers → Absolute Value → Adding Integers → Subtracting Integers → Multiplying Integers → Dividing Integers → Unit Rates → Proportions → Percent Concept → Converting Between Fractions, Decimals, and Percents → Operations with Rational Numbers → Two-Step Equations → Solving Multi-Step Equations → Equations with Variables on Both Sides → Angle Pairs: Complementary, Supplementary, and Vertical → Parallel Lines and Transversals → Corresponding Angles → Alternate Interior Angles → Triangle Angle Sum Theorem → Exterior Angle Theorem → Triangle Inequality Theorem → Similar Triangles: AA Similarity → Similar Triangles: SSS and SAS Similarity → Proportions in Similar Triangles → Right Triangle Trigonometry Introduction → Sine, Cosine, and Tangent Ratios → Trigonometric Ratios Review → Radian Measure → Converting Between Degrees and Radians → The Unit Circle → Graphing Sine and Cosine → Graphing Tangent and Reciprocal Trigonometric Functions → Derivatives of Trigonometric Functions → Antiderivatives → Iterated Integrals and Fubini's Theorem → Double Integrals in Cartesian Coordinates → Double Integrals in Polar Coordinates → Double Integrals in Polar Coordinates → Double Integrals: Definition and Setup → Iterated Integrals and Fubini's Theorem → Double Integrals over Rectangular Regions → Double Integrals over General Regions → Applications of Double Integrals: Area, Mass, and Moments → Triple Integrals in Cartesian Coordinates → Triple Integrals in Cylindrical and Spherical Coordinates → Change of Variables and the Jacobian Determinant → Applications of Triple Integrals: Volume and Mass → Vector Fields and Their Representations → Line Integrals of Vector Fields → Work and Circulation → Line Integrals of Scalar and Vector Functions → Fundamental Theorem for Line Integrals → Conservative Vector Fields → Conservative Vector Fields and Potential Functions → Curl and Divergence of Vector Fields → Curl and Divergence → Divergence Theorem → Electric Flux and Divergence Theorem → Gauss's Law: Integral Form and Meaning → Solving Problems with Gauss's Law → Conductors in Electrostatic Equilibrium → Capacitance and Capacitors → Dielectrics → Dielectric Constant and Relative Permittivity → Electric Field Inside Dielectric Materials → Dielectric Materials and Polarization → Dielectric Susceptibility and Permittivity → Energy Density in Electric Fields → Electric Current and Current Density → Electrical Resistance and Resistivity → Ohm's Law and Circuit Elements → Electromotive Force (EMF) and Batteries → Kirchhoff's Circuit Laws: Voltage and Current → DC Circuit Network Analysis Methods → Transient Response in RC Circuits → RC Circuits → LC and RLC Circuits → AC Circuits: Fundamentals → Impedance and Reactance → AC Power and Resonance → Electromagnetic Waves → Postulates of Special Relativity → Time Dilation → Length Contraction → Lorentz Transformation → Relativistic Velocity Addition → Relativistic Momentum and Energy → Mass-Energy Equivalence and E=mc² → Photons as Particles with Energy and Momentum → Planck-Einstein Relation: Energy and Frequency → Photoelectric Effect → The Photon: Light as Quanta → Compton Scattering → Wave-Particle Duality → de Broglie Wavelength → The Schrödinger Equation → State Vectors and Wavefunctions → Quantum Superposition → The Measurement Problem → Interpretations of Quantum Mechanics → Postulates of Quantum Mechanics → Observables and Quantum Operators → Commutators and Commutation Relations → Quantum Angular Momentum → Quantum Mechanical Treatment of Hydrogen → Solving the Schrödinger Equation for Hydrogen Atom → Quantum Numbers → Electron Configuration → Periodic Trends → Covalent Bonding → Electronegativity and Bond Polarity → Ionic Bonding → Lewis Structures → VSEPR Theory and Molecular Geometry → Molecular Geometry and Electron Pair Geometry → Molecular Polarity and Dipole Moments → Intermolecular Forces → States of Matter and Phase Changes: Melting, Boiling, and Sublimation → Gas Laws and the Ideal Gas Equation → Gas Stoichiometry and Volume-Volume Calculations → Thermochemistry and Enthalpy → Heat Capacity and Calorimetry → Entropy and Molecular Disorder → Spontaneity and ΔG → Entropy and Gibbs Free Energy → Chemical Equilibrium → Acid-Base Chemistry → Weak Acid Ionization → Weak Base Ionization → Acid and Base Strength: Ka, Kb, and Ionization → Leaving Groups and Nucleofugality → SN2 Substitution Reactions → SN1 Substitution Reactions → E1 Elimination Reactions → Alcohols and Ethers: Structure, Properties, and Nomenclature → Reactions of Alcohols → Aldehydes and Ketones: Structure and Reactivity → Oxidation Reactions in Organic Chemistry → Oxidation of Alcohols to Aldehydes and Ketones → Aldehyde and Ketone Structure and Nomenclature → Nucleophilic Addition to Aldehydes and Ketones → Carboxylic Acids and Their Derivatives → IUPAC Nomenclature of Carbonyls and Carboxylic Acids → IUPAC Nomenclature of Alkenes → Electrophilic Addition to Alkenes → Aromaticity and Benzene → Electrophilic Aromatic Substitution (EAS) → Nucleophilic Aromatic Substitution (SNAr) → Nucleophilic Acyl Substitution → Amines: Structure, Basicity, and Reactions → Amine Reactivity: Nucleophilicity and Basicity → Amino Acid Structure and Properties → Peptide Bonds and Polypeptide Formation → Protein Primary Structure → Protein Secondary Structure → Protein Tertiary Structure → Enzyme Structure and Function → Transcription: DNA to RNA → RNA Types and Structure → RNA Structure and Intramolecular Base Pairing → RNA Processing and Splicing → Translation: RNA to Protein → Ribosomes: Protein Synthesis Machines → Translation: Initiation and Elongation → Post-Translational Modifications → Proteasomal Degradation and Ubiquitin-Mediated Marking → Cell Cycle Regulation and Checkpoints → Cell Cycle Checkpoints: Ensuring Genome Integrity → Cell Cycle Checkpoints and Cancer Prevention → Mitotic Spindle Checkpoint and Chromosome Segregation → Kinetochore Structure and Function → Mitochondria: Structure and Function → Cellular Respiration Overview → Glycolysis → Pyruvate Oxidation → The Krebs Cycle (Citric Acid Cycle) → Electron Transport Chain → ATP Synthesis and Oxidative Phosphorylation → ATP Hydrolysis and Cellular Free Energy → The Na+/K+-ATPase: Maintaining Ion Gradients → Resting Membrane Potential → Ligand-Gated Ion Channels → Voltage-Gated Sodium Channels → Action Potential Phases → Postsynaptic Currents: EPSCs and IPSCs → Long-Term Potentiation → NMDA Receptors and Ca2+-Dependent Signaling in Synaptic Plasticity → Dendritic Spine Morphology and Structural Plasticity → Long-Term Depression

Longest path: 236 steps · 1243 total prerequisite topics

Prerequisites (5)

Postsynaptic Currents: EPSCs and IPSCshard Ionotropic vs. Metabotropic Receptorshard Calcium Signaling in Neuronshard Glutamatergic Excitation: Information Transfer and Synaptic Plasticityhard Dendritic Spine Morphology and Structural Plasticitysoft

Leads To (6)

Cerebellum: Motor Coordination and Learninghard Cerebellum: Motor Learning and Coordinationhard Hippocampus: Declarative Memory and Spatial Codinghard Long-Term Depression (LTD): Synaptic Weakeninghard Motor Learning and Cerebellar Adaptationhard Spike-Timing-Dependent Plasticityhard