Ventral hippocampal cholecystokinin interneurons gate contextual reward memory

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Cellular Neuroscience

Background:

• Context-reward association relies on hippocampal circuits.
• Inhibitory interneurons within the hippocampus are critical for modulating neural activity.
• Understanding hippocampal microcircuits is key to deciphering memory formation.

Purpose of the Study:

• To investigate the role of ventral hippocampus (vHPC) to nucleus accumbens (NAc) circuits in context-reward memory.
• To determine the specific contribution of cholecystokinin (CCK) interneurons in gating this circuit.
• To elucidate the mechanism by which CCK interneurons influence reward learning.

Main Methods:

• Utilized a sucrose conditioned place preference (CPP) task.
• Employed optogenetics to manipulate vHPC-NAc terminal activity and CCK interneurons.
• Applied transsynaptic rabies tracing to identify neural connections.
• Used intersectional genetics for targeted manipulation of CCK interneurons.

Main Results:

• Optogenetic inhibition of vHPC-NAc terminals impaired place preference acquisition.
• CCK interneurons directly innervate vHPC-NAc projection neurons.
• Activation of CCK interneurons increased GABAergic transmission onto vHPC-NAc neurons.
• Inhibition of CCK interneurons enhanced contextual reward memory during CPP learning.

Conclusions:

• A vHPC to NAc circuit gated by CCK interneurons is crucial for encoding context-reward memories.
• CCK interneurons modulate the strength of hippocampal-based reward learning.
• This study reveals a novel hippocampal microcircuit involved in reward memory modulation.