2000 Nobel Prize in Physiology or Medicine
Reason for Award
for their discoveries concerning signal transduction in the nervous system
Laureates
Sweden
United States of America
United States of America
Explanation
Our bodies have “nerves” that carry messages from the brain. Mr. Carlsson, Mr. Greengard and Mr. Kandel studied how these nerves “talk” to each other. They discovered that a substance called dopamine works like gasoline for nerves and that a shortage makes it hard for the body to move. They also showed that tiny packets burst at the nerve ending and deliver chemical letters to the next nerve. Repeating a signal makes the pathway thicker and helps us remember things longer. These findings help doctors make medicines for Parkinson’s disease and explain how learning works.
Related Keywords
neurotransmitter
A chemical released by a neuron at the synapse to convey information to an adjacent cell. There are many kinds, such as acetylcholine and dopamine, each exerting excitatory or inhibitory effects. Binding to receptors opens ion channels or activates G-protein-coupled signaling pathways. Inside the postsynaptic cell, second messengers are generated and can ultimately influence gene expression. Imbalances contribute to the onset of neurological and psychiatric diseases.
dopamine
A catecholamine neurotransmitter crucial for motor control, reward and attention. Deficiency in the substantia nigra–striatal pathway triggers Parkinson’s disease, whereas excess in the mesolimbic pathway is linked to schizophrenia-like symptoms. Metabolized by monoamine oxidase and COMT, making these enzymes pharmacological targets. Carlsson’s work led to the clinical adoption of L-DOPA replacement therapy.
synapse
The junction at which a neuron communicates with another cell or a muscle fiber. Presynaptic terminals contain vesicles filled with neurotransmitter that are released in a calcium-dependent manner when an action potential arrives. The chemical diffuses across the synaptic cleft and binds postsynaptic receptors, eliciting electrical and biochemical responses. Plastic modifications in synaptic strength and number provide the substrate for learning and memory. Synaptic dysfunction is implicated in epilepsy, autism and other disorders.
protein phosphorylation
An enzymatic reaction that adds a phosphate group to serine, threonine or tyrosine residues, catalyzed by kinases. Alters protein conformation and charge, thereby regulating enzyme activity and protein-protein interactions. In neurons it functions as a rapid switch that modulates ion channel gating, receptor sensitivity and gene transcription. Greengard elucidated this mechanism in detail through PKA and DARPP-32. Dysregulated phosphorylation is pivotal in pathologies such as tau aggregation in Alzheimer’s disease.
synaptic plasticity
Experience-dependent changes in synaptic strength or number within neural circuits. Short-term plasticity lasts seconds to minutes, whereas long-term plasticity lasts hours to a lifetime. Calcium influx, activation of PKA/PKC and CREB-dependent transcription constitute its molecular basis. Kandel used Aplysia to dissociate and identify the temporal and molecular pathways of short- and long-term plasticity. Understanding plasticity is crucial for elucidating learning mechanisms and designing rehabilitation strategies.
long-term potentiation (LTP)
A long-lasting increase in synaptic efficacy following high-frequency stimulation. In hippocampal CA1 it is NMDA-receptor dependent and accompanied by AMPA-receptor insertion and dendritic spine growth. CREB activation and de novo protein synthesis are essential for maintenance. Considered a cellular model of learning and memory and is impaired in Alzheimer’s models. Kandel’s work showed that LTP-like phenomena are evolutionarily conserved even in invertebrates.
second messenger
A small molecule produced inside the cell after membrane receptor activation that amplifies and propagates a signal. Classic examples include cAMP, IP3 and Ca2+. They activate target kinases or ion channels to elicit physiological responses. Their concentrations are tightly regulated in time and space, ensuring precision in synaptic plasticity and hormone responses. Excess or deficiency can precipitate metabolic or psychiatric disorders.
Aplysia
A large sea slug native to the Californian coast that possesses simple, giant neurons. Kandel devised learning tasks such as sensitization and habituation using Aplysia, allowing identification of individual neuron activity. The model permits direct measurement of neural plasticity at cellular and molecular resolutions. Serotonin application induces short-term facilitation, while repeated stimulation elicits long-term enhancement, making it a standard system for memory research. Demonstration of mechanisms conserved in mammals has reinforced the universality of learning principles.
protein kinase A (PKA)
A serine/threonine kinase activated upon binding cAMP. Catalytic subunits are released from inhibitory regulatory subunits and phosphorylate diverse substrates. In synapses it acts on ion channels, transcription factor CREB, DARPP-32 and more. Greengard showed that the PKA pathway is pivotal for converting receptor stimulation into prolonged cellular responses. Hyperactivity is linked to heart failure and tumorigenesis, whereas hypoactivity is associated with memory deficits.
signal transduction pathway
A mechanism by which a receptor senses an extracellular stimulus and transmits information through intracellular molecular cascades. It proceeds through hierarchical stages of ligand binding, second messenger generation, kinase activation and transcriptional control. Specificity is ensured by spatial compartmentalization and scaffold-protein complex formation. In the nervous system it integrates signals across time scales from milliseconds to hours. The Nobel-winning studies mapped exemplary signal transduction pathways at the molecular level in neurons.