Perineuronal nets on CA2 pyramidal cells and parvalbumin-expressing cells differentially regulate hippocampal...

Area of Science:

• Neuroscience
• Molecular Biology
• Behavioral Science

Background:

• Perineuronal nets (PNNs) are extracellular matrices surrounding specific neurons, including CA2 pyramidal cells and parvalbumin (PV) interneurons.
• PNNs are implicated in regulating synaptic plasticity, learning, and memory.
• Current methods like chondroitinase degradation do not distinguish PNN functions on distinct neuronal populations.

Purpose of the Study:

• To investigate the specific roles of PNNs on CA2 pyramidal cells versus PV interneurons in regulating behavior.
• To disentangle the contributions of PNNs in different hippocampal cell types to social, fear, and spatial memory, as well as reversal learning.

Main Methods:

• Generated conditional knockout mice lacking aggrecan (Acan), a key PNN component, specifically in CA2 pyramidal cells (Amigo2 Acan KO) or PV cells (PV Acan KO).
• Assessed social memory, fear memory, spatial memory, and reversal learning in male and female KO and wild-type mice.
• Investigated neural circuit mechanisms underlying social memory deficits in Amigo2 Acan KO mice, including supramammillary nucleus (SuM) input to CA2 and social novelty-related neural responses.

Main Results:

• Amigo2 Acan KO mice exhibited deficits in social memory and reversal learning, while PV Acan KO mice showed impaired contextual fear memory.
• These results indicate cell-type-specific functions of PNNs in hippocampal-dependent memory processes.
• Amigo2 Acan KO mice displayed reduced SuM input to CA2 and lacked social novelty-related local field potential responses, suggesting PNNs coordinate functional connections and responses to social novelty.

Conclusions:

• PNNs on CA2 pyramidal cells and PV interneurons play distinct and independent roles in regulating specific types of hippocampal-dependent memory.
• PNNs on CA2 neurons are crucial for social memory and reversal learning, potentially by coordinating inputs related to social novelty.
• PNNs on PV interneurons are essential for contextual fear memory.