Summary: According to research, the NMDA receptor ( NMDAR ), which is renowned for its influence on memory and learning, also regulates brain activity by establishing the neural network’s baseline activity. This stability encourages the body’s ability to adapt to changing circumstances both physically and psychologically.
This foundation was disrupted by blocking NMDARs, which was revealed in the study, highlighting their crucial role in maintaining neurological homeostasis. Results may improve treatments for conditions like depression, Alzheimer’s, and seizure by leveraging NMDAR’s function in brain balance.
Important Information:
- NMDARs establish foundation levels of brain activity, which helps to stabilize neural network.
- Blocking NMDARs disrupts foundation treatment, impairing brain balance.
- Advancements in NMDAR work may be the basis for more potent treatments for depression and seizure.
Origin: Tel Aviv University
The NMDA receptor ( NMDAR ), which has been largely studied for its function in memory and learning, also plays a crucial role in stabilizing brain activity, according to researchers at Tel Aviv University.
The NMDAR helps maintain robust mind work in the face of ongoing environmental and physiological changes by setting the “baseline” level for action in neural network.
This finding may lead to modern treatments for illnesses linked to disrupted neurological security, such as melancholy, Alzheimer’s disease, and seizures.
The research was led by Dr. Antonella Ruggiero, Leore Heim, and Dr. Lee Susman from Prof. Inna Slutsky’s test at the University of Medicial and Health Sciences at Tel Aviv University. Prof. Slutsky, who is also affiliated with the Sagol School of Neuroscience, heads the Jewish Society for Neuroscience and directs the Sieratzki Institute for Advances in Neuroscience. More scientists included Dr. Ilana Shapira, Dima Hreaky, and Maxim Katsenelson from the University of Medical and Health Sciences at Tel Aviv University, and Prof. Kobi Rosenblum from the University of Haifa.
The study was published in the exclusive journal , Neuron.
” In recent decades, head research has primarily focused on processes that allow data processing, storage, and learning, based on changes in neural connections between nerve cells”, says Prof. Slutsky.
” But the mind’s essential security, or balance, is essential to support these methods. In our laboratory, we examine the systems that maintain this security, and in this research, we focused on the NMDAR—a ligand known to play a part in learning and memory”.
This comprehensive project used three primary research methods: electrophysiological recordings from neurons in both cultured cells ( in vitro ) and living, behaving mice ( in vivo ) within the hippocampus, combined with computational modeling ( in silico ). Each method revealed special insights into how NMDARs affect neuronal network stability.
Dr. Antonella Ruggiero studied NMDAR work in educated cells using an innovative method called “dual perturbation”, developed in Prof. Slutsky’s test.
” First, I exposed neurons to ketamine, a known NMDAR blocker”, she explains.
” Typically, neuronal networks recover on their own after disruptions, with activity levels gradually returning to baseline due to active compensatory mechanisms. But when the NMDAR was blocked, activity levels stayed low and did n’t recover.
” Then, with the NMDAR still blocked, I introduced a second perturbation by blocking another receptor. This time, the activity dropped and recovered as expected, but to a new, lower baseline set by ketamine, not the original level.”
This finding demonstrates that neuronal networks ‘ NMDAR is a crucial component for maintaining and setting the activity baseline. It suggests that NMDAR blockers may alter homeostatic set points as well as synaptic plasticity in behavior.
Building on this discovery, Dr. Ruggiero sought to uncover the molecular mechanisms behind the NMDAR’s role in tuning the set point. She discovered that calcium ions ‘ NMDAR activity allows the antidepressant eEF2K-BDNF signaling pathway, which was previously linked to ketamine’s antidepressant effects.
Leore Heim looked into whether the NMDAR had an impact on living animal baseline activity. A significant technical challenge was recording long-term activity at the individual neuron level while administering an NMDAR blocker directly to the hippocampus without affecting other brain regions.
He explains that “infant studies frequently used injections that delivered NMDAR blockers across the entire brain, leading to inconsistent and sometimes contradictory results.”
I created a technique that combines long-term neural activity recording in the same region with direct drug infusion into the hippocampus to address this. With no compensatory recovery as seen with other drugs, this method revealed a consistent decrease in hippocampal activity across states like wakefulness and sleep.
This demonstrates conclusively that NMDARs establish a baseline for activity in living things ‘ hippocampal networks.
To address a lingering question, mnematician Dr. Lee Susman created computational models to demonstrate whether brain stability is maintained across the entire neural network, or does each neuron maintain its own stabilization?
” Based on the data from Antonella and Leore’s experiments, I found that stability is maintained at the network level, not within single neurons”, he explains.
I demonstrated that varying neuronal activity to the tune of averaging it across multiple neurons results in improved signal propagation and noise reduction. However, we need to better understand the functional significance of single-neuron drift in future studies”.
Prof. Slutsky adds:” We know that ketamine blocks NMDARs, and in 2008, it was FDA-approved as a rapid-acting treatment for depression. Ketamine blocks NMDARs immediately, unlike traditional antidepressants like Cipralex and Prozac. However, until now, it was n’t fully understood how the drug produced its antidepressant effects.
Our findings point to the recently discovered role of NMDAR in lowering the activity baseline in overactive brain regions like the lateral habenula without impairing homeostatic processes.
” This discovery could transform how we think about depression and help us create novel treatments,” he said.
About this news from neuroscience research
Author: Noga Shahar
Source: Tel Aviv University
Contact: Noga Shahar – Tel Aviv University
Image: The image is credited to Neuroscience News
Original Research: Open access.
By Antonella Ruggiero and colleagues,” NMDA receptors regulate the firing rate set point of hippocampal circuits without changing single-cell dynamics.” Neuron
Abstract
Hippocampal circuits ‘ firing rate and set point are controlled by NMDA receptors without altering single-cell dynamics.
A fundamental yet unexplored aspect of neuroscience is how neuronal circuits regulate their activity.
Here, we show that hippocampal network properties, such as firing rate distribution and dimensionality, are actively regulated, despite perturbations and single-cell drift.
Continuous inhibition of N-methyl-D-aspartate receptors ( NMDARs )  , ex , vivo , lowers the excitation/inhibition ratio and network firing rates while preserving resilience to perturbations.
This establishes a new network firing rate set point via NMDAR-eEF2K signaling pathway. NMDARs ‘ capacity to modulate and stabilize network firing is mediated by excitatory synapses and the intrinsic excitability of parvalbumin-positive neurons, respectively.
Continuous NMDAR blockade in CA1 in behaved mice reduces network firing without affecting single-neuron drift or triggering a compensatory response.
These findings expand NMDAR function beyond their canonical synaptic plasticity and raise the possibility that some NMDAR-dependent behavioral effects are mediated by their particular set of population activity regulation mechanisms.
