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Related Concept Videos

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When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of...
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MicroRNA-138-5p suppresses excitatory synaptic strength at the cerebellar input layer.

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MicroRNA-138-5p (miR-138-5p) fine-tunes cerebellar excitatory synapses. Its downregulation enhances synaptic strength and short-term depression via pre- and postsynaptic mechanisms.

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Area of Science:

  • Neuroscience
  • Molecular Biology
  • Synaptic Plasticity

Background:

  • MicroRNAs (miRNAs) are key regulators of gene expression, influencing neuronal development and synaptic function.
  • MicroRNA-138-5p (miR-138-5p) is expressed in cerebellar excitatory neurons, but its role in cerebellar synaptic transmission is unknown.
  • Understanding miRNA roles is crucial for deciphering complex neural circuit regulation.

Purpose of the Study:

  • To investigate the function of miR-138-5p in regulating excitatory synaptic transmission in the adult murine cerebellum.
  • To elucidate the pre- and postsynaptic mechanisms underlying miR-138-5p's influence on cerebellar synapses.

Main Methods:

  • Utilized a miR-138-5p sponge construct in mice to sequester endogenous miR-138-5p.
  • Performed electrophysiological recordings, including mossy fibre stimulation-evoked EPSCs and miniature EPSCs.
  • Conducted high-frequency train stimulation and computational modelling.

Main Results:

  • Downregulation of miR-138-5p significantly increased mossy fibre-evoked EPSCs and miniature EPSC amplitudes in cerebellar granule cells.
  • Observed enhanced short-term depression following miR-138-5p downregulation, indicating altered presynaptic release probability.
  • Results suggest increased functional postsynaptic AMPA receptor numbers.

Conclusions:

  • miR-138-5p negatively regulates excitatory synaptic strength in the cerebellum through both presynaptic and postsynaptic mechanisms.
  • This miRNA acts as a suppressor of synaptic efficacy, influencing release probability and postsynaptic receptor availability.
  • Findings reveal miR-138-5p as a critical modulator of cerebellar excitatory input and short-term plasticity.