Non-Hebbian Long-Term Depression at VIP Interneuron Inputs Selectively Tunes Inhibition in Disinhibitory Circuits of...

Area of Science:

• Neuroscience
• Synaptic Plasticity
• Hippocampal Circuitry

Background:

• Control of synaptic inhibition is crucial for neuronal computation.
• Mechanisms of inhibitory synapse strength adjustment remain largely unknown.
• Inhibitory-inhibitory (I→I) synapses are key for network regulation.

Purpose of the Study:

• To investigate the rules governing plasticity at I→I synapses.
• To characterize a novel form of inhibitory long-term depression (iLTD).
• To determine the cell-type specificity of I→I synaptic plasticity.

Main Methods:

• Whole-cell recordings from hippocampal CA1 oriens interneurons.
• Optogenetic activation of vasoactive intestinal peptide (VIP)-positive interneuron inputs.
• Induction of synaptic plasticity using postsynaptic burst firing protocols.

Main Results:

• Repeated postsynaptic burst firing induced non-Hebbian iLTD at VIP→oriens interneuron synapses.
• This iLTD required postsynaptic calcium influx but was independent of endocannabinoids.
• In contrast, parvalbumin and somatostatin interneuron synapses followed Hebbian rules.

Conclusions:

• A novel, cell-type-specific, non-Hebbian plasticity rule governs I→I synapses.
• This mechanism weakens disinhibition in a manner dependent on activity history.
• Identified a new physiological mechanism modulating gain in hippocampal microcircuits.