Pattern detection in the TGFβ cascade controls the induction of long-term synaptic plasticity.

Area of Science:

• Neuroscience
• Molecular Biology
• Cellular Biology

Background:

• Long-term memory (LTM) formation in Aplysia requires transforming growth factor beta (TGFβ).
• TGFβ inhibition during two-trial training specifically blocks LTM when applied during the second trial, not the first.

Purpose of the Study:

• To investigate the role of TGFβ as a

Main Methods:

• Investigated the necessity of TGFβ proligand secretion and proteolytic activation by Bone morphogenetic protein-1 (BMP-1/Tolloid) during two-trial training.
• Examined the induction of long-term synaptic facilitation (LTF), the cellular correlate of LTM, using BMP-1 application and serotonin (5HT) pulses.
• Assessed the effect of endogenous BMP-1 inhibition on two-trial LTF induction.

Main Results:

• TGFβ acts as a repetition detector for two-trial LTM induction in Aplysia.
• Proteolytic activation of the TGFβ proligand by BMP-1/Tolloid specifically occurs during the second trial of training.
• BMP-1 application combined with a single serotonin (5HT) pulse induced LTF, while either alone did not.
• Inhibition of endogenous BMP-1 activity prevented the induction of two-trial LTF.

Conclusions:

• Repeated stimuli engage distinct steps of the TGFβ cascade during learning.
• This sequential activation of the TGFβ pathway is essential for the induction of long-lasting memories.
• TGFβ plays a unique role in integrating information from repeated learning trials.