RTP801 regulates motor cortex synaptic transmission and learning

Leticia Pérez-Sisqués, Núria Martín-Flores, Mercè Masana, Júlia Solana-Balaguer, Arnau Llobet, Joan Romaní-Aumedes, Mercè Canal, Genís Campoy-Campos, Esther García-García, Núria Sánchez-Fernández, Sara Fernández-García, James P. Gilbert, Manuel José Rodríguez, Heng Ye Man, Elena Feinstein, David L. Williamson, David Soto, Xavier Gasull, Jordi Alberch, Cristina Malagelada

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


Background: RTP801/REDD1 is a stress-regulated protein whose upregulation is necessary and sufficient to trigger neuronal death in in vitro and in vivo models of Parkinson's and Huntington's diseases and is up regulated in compromised neurons in human postmortem brains of both neurodegenerative disorders. Indeed, in both Parkinson's and Huntington's disease mouse models, RTP801 knockdown alleviates motor-learning deficits. Results: We investigated the physiological role of RTP801 in neuronal plasticity and we found RTP801 in rat, mouse and human synapses. The absence of RTP801 enhanced excitatory synaptic transmission in both neuronal cultures and brain slices from RTP801 knock-out (KO) mice. Indeed, RTP801 KO mice showed improved motor learning, which correlated with lower spine density but increased basal filopodia and mushroom spines in the motor cortex layer V. This paralleled with higher levels of synaptosomal GluA1 and TrkB receptors in homogenates derived from KO mice motor cortex, proteins that are associated with synaptic strengthening. Conclusions: Altogether, these results indicate that RTP801 has an important role modulating neuronal plasticity and motor learning. They will help to understand its role in neurodegenerative disorders where RTP801 levels are detrimentally upregulated.

Original languageEnglish (US)
Article number113755
JournalExperimental Neurology
StatePublished - Aug 2021

All Science Journal Classification (ASJC) codes

  • Neurology
  • Developmental Neuroscience


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