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

Area of Science:

• Neuroscience
• Molecular Biology
• Learning and Memory

Background:

• Protein degradation via the ubiquitin proteasome system is vital for learning and synaptic plasticity.
• The role of proteasome activity in learning is complex, with some studies indicating necessity and others suggesting a negative regulatory role.
• Previous research linked N-methyl d-aspartate receptor (NMDAR)-dependent proteasome upregulation to conditioned taste aversion (CTA) formation.

Purpose of the Study:

• To investigate the molecular and cellular mechanisms in the gustatory cortex (GC) underlying appetitive and aversive taste learning.
• To identify upstream and downstream effectors of proteasome activity modulation following novel taste learning.
• To elucidate the role of muscarinic acetylcholine receptors (mAChRs) in regulating proteasome activity during taste memory formation.

Main Methods:

• Assessed proteasome activity in the GC immediately after novel taste consumption.
• Investigated the involvement of mAChRs and NMDARs in modulating proteasome activity.
• Measured p70 S6 kinase (p70S6k) levels following taste learning and pharmacological interventions.
• Utilized proteasome inhibitor lactacystin and mAChR antagonist scopolamine to assess their effects on taste memory.

Main Results:

• A reduction in proteasome-mediated degradation was observed in the GC 20 minutes after novel taste consumption, dependent on mAChRs but independent of NMDARs.
• This reduced degradation led to increased levels of p70 S6 kinase, an effect blocked by scopolamine.
• Infusion of lactacystin into the GC impaired novel taste learning and the increase in p70 S6 kinase, and also blocked the amnestic effect of scopolamine.

Conclusions:

• This study reveals a novel mechanism of cortical, mAChR-dependent reduced proteasome activity immediately following novel taste learning, which facilitates the formation of taste familiarity memory.
• Inhibition of proteasome-mediated degradation in the GC attenuates novel taste learning and the associated increase in p70 S6 kinase.
• These findings highlight the intricate interplay between protein synthesis and degradation pathways in the cortex during the processing of novel taste experiences.