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Neutral Sphingomyelinase is an Affective Valence-Dependent Regulator of Learning and Memory
Liubov S Kalinichenko1, Laila Abdel-Hafiz2, An-Li Wang2
1Department of Psychiatry and Psychotherapy, University Clinic, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen 91054, Germany.
Cerebral Cortex (New York, N.Y. : 1991)
|October 12, 2020
Summary
The sphingolipid rheostat, particularly neutral sphingomyelinase (NSM) activity, plays a key role in learning and memory. Enhanced NSM activity is linked to better appetitive memory, suggesting a novel mechanism for memory formation.
Area of Science:
- Neuroscience
- Biochemistry
- Behavioral Science
Background:
- Sphingolipids and their enzymes regulate synaptic function in the brain.
- The precise role of the sphingolipid rheostat in behavioral plasticity, including learning and memory, is not well understood.
- Different types of memory, such as appetitive and aversive, are thought to involve distinct neural pathways.
Purpose of the Study:
- To investigate the contribution of the sphingolipid rheostat to various dimensions of learning and memory.
- To explore the role of neutral sphingomyelinase (NSM) in appetitively and aversively motivated memory.
- To examine the translational relevance of NSM activity in memory formation across species.
Main Methods:
- Assessed learning and memory performance in tasks involving appetitive and aversive motivation.
- Measured neutral sphingomyelinase (NSM) activity in specific brain regions and serum.
- Utilized genetically modified mice with reduced NSM activity.
- Investigated the relationship between NSM activity, N-methyl-d-aspartate receptor subunit expression, and memory performance.
- Conducted translational studies in nonhuman primates and humans.
Main Results:
- Superior short- and long-term appetitively motivated learning correlated with enhanced regional NSM activity.
- An inverse relationship between NSM activity and aversively motivated memory was observed.
- Mice with genetically reduced NSM activity exhibited impaired learning, confirming a valence-dissociating role for NSM.
- NSM's role in memory may involve the regulation of N-methyl-d-aspartate receptor subunit expression.
- Serum NSM activity positively associated with long-term appetitively motivated memory in primates and humans.
Conclusions:
- Neutral sphingomyelinase (NSM) activity is a critical component of the sphingolipid rheostat that influences learning and memory.
- NSM exhibits a valence-dissociating role, promoting appetitive memory while potentially hindering aversive memory.
- These findings suggest a novel sphingolipid-based mechanism for de novo learning and memory, with translational implications for human cognition.
