Restoring auditory cortex plasticity in adult mice by restricting thalamic adenosine signaling

Science. 2017 Jun 30;356(6345):1352-1356. doi: 10.1126/science.aaf4612.

Abstract

Circuits in the auditory cortex are highly susceptible to acoustic influences during an early postnatal critical period. The auditory cortex selectively expands neural representations of enriched acoustic stimuli, a process important for human language acquisition. Adults lack this plasticity. Here we show in the murine auditory cortex that juvenile plasticity can be reestablished in adulthood if acoustic stimuli are paired with disruption of ecto-5'-nucleotidase-dependent adenosine production or A1-adenosine receptor signaling in the auditory thalamus. This plasticity occurs at the level of cortical maps and individual neurons in the auditory cortex of awake adult mice and is associated with long-term improvement of tone-discrimination abilities. We conclude that, in adult mice, disrupting adenosine signaling in the thalamus rejuvenates plasticity in the auditory cortex and improves auditory perception.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5'-Nucleotidase / metabolism
  • Adenosine / administration & dosage
  • Adenosine / analogs & derivatives
  • Adenosine / metabolism*
  • Adenosine A1 Receptor Agonists / administration & dosage
  • Adenosine A1 Receptor Antagonists / administration & dosage
  • Animals
  • Auditory Cortex / metabolism*
  • Auditory Perception
  • GPI-Linked Proteins / metabolism
  • Mice
  • Neuronal Plasticity
  • Piperidines / administration & dosage
  • Pyridazines / administration & dosage
  • Receptor, Adenosine A1 / metabolism
  • Signal Transduction*
  • Thalamus / metabolism

Substances

  • 2-(1-methyl-4-piperidinyl)-6-(2-phenylpyrazolo(1,5-a)pyridin-3-yl)-3(2H)-pyridazinone
  • Adenosine A1 Receptor Agonists
  • Adenosine A1 Receptor Antagonists
  • GPI-Linked Proteins
  • Piperidines
  • Pyridazines
  • Receptor, Adenosine A1
  • 2-chloro-N(6)cyclopentyladenosine
  • 5'-Nucleotidase
  • Nt5e protein, mouse
  • Adenosine