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Inside the Hippocampus: The Role of PNNs

Explore how PNNs influence memory in the brain's hippocampus.

Georgia M. Alexander, Viktoriya D. Nikolova, Tristan M. Stöber, Artiom Gruzdev, Sheryl S. Moy, Serena M. Dudek

― 5 min read


PNNs and Memory in CA2PNNs and Memory in CA2processing.Study reveals PNNs' key role in memory
Table of Contents

The Hippocampus is a part of the brain that helps us remember things, like where we put our keys or that one embarrassing moment from high school. It's like a storage room for memories. Within the hippocampus, there are different areas that each play their own role, much like how different rooms in a house serve different purposes.

Meet Area CA2

One special room in this memory house is called area CA2. It has some unique features that set it apart from other rooms. For instance, it has a specific mix of chemicals that help it work differently. CA2 is also important for Social Memory, which is how we remember people and our interactions with them.

What Are Perineuronal Nets?

Within CA2, there are special structures called perineuronal nets (PNNs) that wrap around certain brain cells. Think of PNNs like cozy, protective blankets that help keep these cells warm and happy. They help stabilize connections between brain cells and also play a role in how flexible our brains can be when learning new things. If these PNNs aren't working right, it might be harder for our brains to make or change memories.

PNNs and Social Memory

Our brains, specifically CA2, work hard to help us remember social situations. For example, when we meet someone new, our brains are busy storing that information for future use. Research has shown that as PNNs develop, we start to get better at recognizing new people. If the PNNs don't work properly, it can mess up our ability to remember social interactions.

Research Approaches

To study how PNNs affect memory, scientists have used a method called chondroitinase treatment, which helps break down PNNs. However, this approach also affects other types of cells, so researchers wanted to be more specific in their studies. They created genetically modified mice that could help them understand the role of PNNs specifically in CA2 neurons without bothering the surrounding cells.

The Special Mice

The scientists created mice with “floxed” genes, which are like special switches that can be turned off in specific cells. By switching off the gene that makes PNNs in CA2 neurons, researchers could see how this affected memory and behavior. They then tested these mice in various memory tasks to see what happened when the PNNs were removed from CA2 neurons but kept in other types of cells.

Testing Memory Types

The researchers tested the modified mice in a number of ways. One test included letting the mice interact with novel and familiar social characters, like a classic game of “who's that?” They watched how much time the mice spent with a new buddy versus an old acquaintance. This gave them insights into the social memory of the mice-who remembered who and how well.

In another test, they used a water maze to assess Spatial Memory. Here, mice had to find a hidden platform in a big pool of water (a bit like a mouse version of "find the treasure"). They tracked how fast the mice could find the platform and if they could remember where it was located the next time, and if they could adjust to when the platform was moved, which is called reversal learning.

Results: Social Memory Challenges

The researchers found that when they took away PNNs from CA2 neurons, the mice struggled to remember social connections. In simpler terms, it's like going to a party and forgetting everyone’s name after being introduced. The mice couldn’t tell the difference between an old friend and a new acquaintance.

Interestingly, when the PNNs were removed from another type of cell called PV interneurons, the mice didn't face the same social memory issues. This showed that PNNs on CA2 neurons were specifically important for social memory.

Results: Water Maze Trials

Moving on to the water maze tests, the mice with edited CA2 neurons could still find the platform when it was in its original spot, suggesting their spatial memory was intact. But once it was time to find the new location of the platform, things didn’t go as smoothly. These mice tended to forget where the platform was and wandered around the maze aimlessly, much like a lost tourist without GPS.

In contrast, the mice that still had their PNNs in the CA2 neurons performed better in the reversal learning task, showcasing their ability to adapt and learn new spatial information. It appears that the PNNs played a vital role in helping the brain adjust as situations change.

Why Are PNNs Important?

PNNs have a critical role in keeping everything organized within the brain's memory centers. They help make connections between neurons secure and stable, thus assisting our brain in coding and retaining memories.

Without these nets, it seems that the flow of information among neurons falters, leading to forgetfulness, especially in social situations. That’s probably why someone might forget a friend’s birthday or which item to grab at the grocery store!

The Bigger Picture

This research opens doors for understanding memory better and could even lead to finding new treatments for memory-related issues, such as those encountered in conditions like Alzheimer’s disease or autism.

So, the next time you struggle to recall a name or navigate a new area, you might just blame it on the absence of your inner brain nets-the helpful PNNs that keep everything in check!

Conclusion

In summary, area CA2, with its unique PNNs, plays a vital role in both social and spatial memory. The research shows us that the right kind of support in our brain can help us remember the important things in life-like not forgetting the names of people you just met at a party! And let’s be honest: isn’t that something worth remembering?

Original Source

Title: Perineuronal nets on CA2 pyramidal cells and parvalbumin-expressing cells differentially regulate hippocampal dependent memory

Abstract: Perineuronal nets (PNNs) are a specialized extracellular matrix that surround certain populations of neurons, including (inhibitory) parvalbumin (PV) expressing-interneurons throughout the brain and (excitatory) CA2 pyramidal neurons in hippocampus. PNNs are thought to regulate synaptic plasticity by stabilizing synapses and as such, could regulate learning and memory. Most often, PNN functions are queried using enzymatic degradation with chondroitinase, but that approach does not differentiate PNNs on CA2 neurons from those on adjacent PV cells. To disentangle the specific roles of PNNs on CA2 pyramidal cells and PV neurons in behavior, we generated conditional knockout mouse strains with the primary protein component of PNNs, aggrecan (Acan), deleted from either CA2 pyramidal cells (Amigo2 Acan KO) or from PV cells (PV Acan KO). Male and female animals of each strain were tested for social, fear, and spatial memory, as well as for reversal learning. We found that Amigo2 Acan KO animals, but not PV Acan KO animals, had impaired social memory and reversal learning. PV Acan KOs, but not Amigo2 Acan KOs had impaired contextual fear memory. These findings demonstrate independent roles for PNNs on each cell type in regulating hippocampal-dependent memory. We further investigated a potential mechanism of impaired social memory in the Amigo2 Acan KO animals and found reduced input to CA2 from the supramammillary nucleus (SuM), which signals social novelty. Additionally, Amigo2 Acan KOs lacked a social novelty-related local field potential response, suggesting that CA2 PNNs may coordinate functional SuM connections and associated physiological responses to social novelty. SIGNIFICANCE STATEMENTPerineuronal nets (PNNs) surround both inhibitory parvalbumin (PV)-expressing neurons and excitatory CA2 pyramidal neurons, but previous studies using enzymatic degradation cannot differentiate the relative roles of PNNs in the two populations. By conditionally deleting aggrecan (Acan) from CA2 pyramidal neurons without affecting PNNs on PV cells, and vice versa, we discovered distinct roles of PNNs on each cell type in behavior. Social memory, which requires CA2 activity, was impaired in mice lacking CA2 PNNs, but not in those lacking PV PNNs. Cognitive flexibility, assessed by reversal learning was also impaired in mice lacking CA2 PNNs, whereas contextual fear memory was impaired in those lacking PV PNNs. Thus, PNNs on each cell type differentially contribute to different forms of hippocampal-dependent memory.

Authors: Georgia M. Alexander, Viktoriya D. Nikolova, Tristan M. Stöber, Artiom Gruzdev, Sheryl S. Moy, Serena M. Dudek

Last Update: 2024-11-08 00:00:00

Language: English

Source URL: https://www.biorxiv.org/content/10.1101/2024.11.07.622463

Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.07.622463.full.pdf

Licence: https://creativecommons.org/publicdomain/zero/1.0/

Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.

Thank you to biorxiv for use of its open access interoperability.

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