Entorhinal cortical Island cells regulate temporal association learning with long trace period

Area of Science:

• Neuroscience
• Cognitive Science
• Learning and Memory

Background:

• Temporal association learning (TAL) links events separated in time.
• The entorhinal cortical-hippocampal network, particularly medial entorhinal cortex layer III (MECIII) projections to hippocampal CA1, is vital for TAL.
• Medial entorhinal cortex layer II (MECII) 'Island cells' influence TAL with weak stimuli, but their role in long temporal gaps is unknown.

Purpose of the Study:

• To investigate the role of MECII Island cells in regulating the duration of the temporal gap in TAL.
• To determine if Island cells limit the learnable trace period in long trace fear conditioning (L-TFC).

Main Methods:

• Pavlovian trace fear conditioning (TFC) with a 60-sec trace period (L-TFC).
• Optogenetic and chemogenetic manipulation of Island cell activity.
• Cell type-specific neural ablation of Island cells.

Main Results:

• Ablation of MECII Island cells partially enhanced L-TFC performance.
• Chemogenetic manipulation disrupted L-TFC due to circuit imbalance.
• Optogenetic inhibition of Island cell projections to hippocampal CA1 during the trace period enabled learning of long temporal intervals.

Conclusions:

• MECII Island cells play a critical role in regulating the duration of temporal intervals that can be bridged during TAL.
• Island cells appear to act as a gate or limiter on the temporal window for associative learning.