Dual Role of an mps-2/KCNE-Dependent Pathway in Long-Term Memory and Age-Dependent Memory Decline

Bank G Fenyves1, Andreas Arnold2, Vaibhav G Gharat2

  • 1Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Division of Molecular Neuroscience, Department of Psychology, University of Basel, Birmannsgasse 8, 4055 Basel, Switzerland; Department of Molecular Biology, Semmelweis University, Tűzoltó u. 37-47, 1094 Budapest, Hungary.

Current Biology : CB
|December 1, 2020
PubMed

Insights

The MPS-2 protein regulates long-term associative memory (LTAM) in C. elegans and prevents age-dependent memory decline by modulating potassium channels. This pathway is crucial for memory formation and healthy aging.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • Neuronal plasticity underlies learning and memory.
  • Voltage-gated potassium (Kv) channels regulate neuronal excitability and may be involved in age-related memory dysfunction.
  • MinK-related peptides (MiRPs) modulate Kv channels, but their role in memory is unknown.

Purpose of the Study:

  • Investigate the role of MiRPs in long-term associative memory (LTAM) and age-dependent memory decline in C. elegans.
  • Identify the specific MiRP family member and its associated molecular pathways involved in memory regulation.
  • Elucidate the mechanisms by which MPS-2 influences neuronal function and memory across the lifespan.

Main Methods:

  • Utilized C. elegans as a model organism.
  • Conducted genetic screens and molecular analyses to identify the mps-2 gene and its regulatory elements.
  • Performed behavioral assays to assess LTAM and age-dependent memory.
  • Investigated gene expression patterns and protein interactions using transcriptional and post-transcriptional analysis.
  • Examined the functional impact of MPS-2 on specific potassium channels (KVS-3 and KVS-4).

Main Results:

  • Identified mps-2 as the sole MiRP family member in C. elegans regulating LTAM in AVA neurons.
  • Demonstrated that mps-2 plays a critical role in preventing age-dependent memory decline.
  • Showed that CRH-1/cyclic AMP (cAMP)-response-binding protein (CREB) upregulates mps-2 during LTAM in young worms.
  • Revealed that the transcription factor nhr-66 acts as an age-dependent repressor of mps-2 baseline expression.
  • Found that deleting nhr-66 or its binding site prevents age-dependent repression of mps-2 and subsequent memory loss.
  • Established that MPS-2 modulates Kv2.1/KVS-3 and Kv2.2/KVS-4 heteromeric potassium channels.

Conclusions:

  • The MPS-2/KVS-3/KVS-4 pathway is essential for LTAM in C. elegans.
  • MPS-2 is a key regulator of physiological age-dependent memory decline.
  • Understanding this pathway offers insights into conserved mechanisms of memory maintenance and aging.

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