Hippocampal Interneurons are Required for Trace Eyeblink Conditioning in Mice

Area of Science:

• Neuroscience
• Cellular mechanisms of learning

Background:

• The hippocampus is crucial for associating events separated in time.
• Cellular mechanisms underlying this hippocampal function remain unclear.

Purpose of the Study:

• Investigate the role of hippocampal interneurons in associative learning using a trace eyeblink conditioning (tEBC) task.
• Clarify the cellular mechanisms involved in learning time-separated associations.

Main Methods:

• Utilized in vivo multi-channel recording and optogenetics in freely-moving mice.
• Monitored hippocampal interneuron and pyramidal cell activity during tEBC.
• Manipulated hippocampal interneuron activity via optogenetic suppression.

Main Results:

• Hippocampal interneurons displayed conditioned stimulus (CS)-evoked sustained activity during early tEBC acquisition, predicting conditioned eyeblink responses (CRs).
• A larger proportion of hippocampal pyramidal cells showed CS-evoked decreased activity during early acquisition.
• Optogenetic suppression of interneuron sustained activity significantly hindered tEBC acquisition.
• Suppression did not affect performance of well-learned CRs.

Conclusions:

• Hippocampal interneurons play a critical role in the acquisition of trace eyeblink conditioning.
• Sustained interneuron activity is a potential cellular mechanism for associative learning.
• This interneuron activity is specific to the learning phase, not the performance of established memories.