Inhibitory Neurons Marked by the Connectivity Molecule Kirrel3 Regulate Memory Precision.

Area of Science:

• Neuroscience
• Molecular Biology
• Genetics

Background:

• Kirrel3 (a homophilic adhesion molecule) is crucial for synapse formation between dentate granule (DG) and GABA neurons.
• Kirrel3 gene variants are linked to human neurodevelopmental disorders.
• The specific circuit function and behavioral relevance of Kirrel3-expressing neurons remain largely unknown.

Purpose of the Study:

• To identify and characterize the function of Kirrel3-expressing neurons in the adult brain.
• To investigate the role of these neurons in memory discrimination and retrieval.
• To link molecular identity (Kirrel3 expression) with specific neuronal circuit function and behavior.

Main Methods:

• Utilized intersectional genetics to identify Kirrel3-expressing GABA neurons.
• Employed chemogenetics, in vivo electrophysiology, and behavioral assays in mice.
• Conducted light and electron microscopy to examine neuronal connections.

Main Results:

• Identified a population of Kirrel3-expressing GABA neurons regulating memory discrimination in male and female mice.
• Demonstrated that activating these neurons inhibits CA3 neuron activity and impairs contextual memory discrimination during recall.
• Observed that Kirrel3-expressing GABA neurons receive excitation from DG neurons and project to CA3 neuron dendrites.

Conclusions:

• Kirrel3-expressing GABA neurons play a critical role in the retrieval of precise memories.
• These neurons exert strong inhibitory control over CA3 neuron activity, influencing memory precision.
• The study establishes a framework connecting molecular identity, synaptic specificity, and behavioral function.