Perineuronal Nets on CA2 Pyramidal Cells and Parvalbumin-Expressing Cells Differentially Regulate...

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Perineuronal nets (PNNs) are extracellular matrices regulating synaptic plasticity and memory.
• Current methods like chondroitinase degradation lack cell-type specificity for PNN function.
• Disentangling PNN roles on specific neuronal populations is crucial for understanding brain function.

Purpose of the Study:

• To investigate the distinct roles of PNNs on CA2 pyramidal cells versus PV interneurons in regulating behavior.
• To generate and analyze cell-type-specific aggrecan knock-out mouse models for PNN research.

Main Methods:

• Generated Amigo2-Cre;Acan-floxed (Amigo2 Acan KO) and PV-Cre;Acan-floxed (PV Acan KO) mice to delete aggrecan, a key PNN protein, from CA2 or PV cells, respectively.
• Assessed social, fear, and spatial memory, along with reversal learning, in male and female KO and wild-type mice.
• Investigated neural circuit mechanisms underlying social memory deficits in Amigo2 Acan KO mice.

Main Results:

• Amigo2 Acan KO mice exhibited deficits in social memory and reversal learning.
• PV Acan KO mice showed impaired contextual fear memory.
• Amigo2 Acan KO mice displayed reduced supramammillary nucleus (SuM) input to CA2 and lacked social novelty-related neural responses.

Conclusions:

• PNNs on CA2 pyramidal cells and PV interneurons play independent, cell-type-specific roles in hippocampal-dependent memory.
• CA2 PNNs are critical for processing social novelty via SuM inputs.
• This study provides novel insights into the specific functions of PNNs in distinct neuronal circuits.