mAChR-dependent decrease in proteasome activity in the gustatory cortex is necessary for novel taste learning

Tali Rosenberg, Alina Elkobi, Kobi Rosenblum

Research output: Contribution to journalArticlepeer-review

Abstract

Regulation of protein degradation via the ubiquitin proteasome system is crucial for normal learning and synaptic plasticity processes. While some studies reveal that increased proteasome degradation is necessary for different types of learning, others suggest the proteasome to be a negative regulator of plasticity. We aim to understand the molecular and cellular processes taking place in the gustatory cortex (GC), which underlie appetitive and aversive forms of taste learning. Previously, we have shown that N-methyl D-aspartic acid receptor (NMDAR)-dependent upregulation of proteasome activity 4 h after novel taste learning is necessary for the association of novel taste with malaise and formation of conditioned taste aversion (CTA). Here, we first identify a correlative increase in proteasome activity in the GC immediately after novel taste learning and study the upstream and downstream effectors of this modulated proteasome activity. Interestingly, proteasome-mediated degradation was reduced in the GC, 20 min after novel taste consumption in a muscarinic acetylcholine receptor (mAChR)-dependent and NMDAR-independent manner. This reduction in protein degradation led to an increased amount of p70 S6 kinase (p70S6k), which was abolished in the presence of mAChR antagonist scopolamine. Infusion of lactacystin, a proteasome inhibitor, to the GC precluded the amnestic effect of scopolamine. This study shows for the first time that following novel taste learning there is a cortical, mAChR-dependent reduced proteasome activity that enables the memory of taste familiarity. Moreover, inhibition of degradation in the GC attenuates novel taste learning and of p70 S6 kinase correlative increased expression. These results shed light on the complex regulation of protein synthesis and degradation machineries in the cortex following novel taste experience.

Original languageEnglish
Pages (from-to)115-124
Number of pages10
JournalNeurobiology of Learning and Memory
Volume135
DOIs
StatePublished - Nov 2016

Bibliographical note

Funding Information:
This work was supported by the Israel Science Foundation (ISF 2395/15), European Union Seventh Framework Program EUROSPIN (Contract HEALTH-F2-2009-241498), and the German-Israeli Foundation DIP (RO3971/1-1) grants to KR. We thank the laboratory members of KR, specifically Dr. Shunit Gal Ben-Ari for critical reading of the manuscript. The authors declare no competing financial interests.

Publisher Copyright:
© 2016 Elsevier Inc.

Keywords

  • Attenuation of neophobia
  • Gustatory cortex
  • Proteasome
  • Scopolamine
  • mAChR
  • p70S6k

ASJC Scopus subject areas

  • Experimental and Cognitive Psychology
  • Cognitive Neuroscience
  • Behavioral Neuroscience

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