Summary: Scientists have discovered how the CP-AMPA receptor affects nerve sensitivity in response to visual stimuli. Neuronal selection is less compromised by this receptor form, which may explain some mental conditions like autism and seizures.
Experts observed changes in physical and geographic processing by manipulating these receptor in mice. These observations, including intellectual disability, could lead to novel therapies for situations involving misfiring neurons.
Important Information:
- CP-AMPA receptor reduce nerve sensitivity, impacting visual response.
- Autism and academic illness are related to abnormalities in associated proteins.
- This improved nerve sensitivity and stability by manipulating these receptor in mice.
Origin: Johns Hopkins Medicine
According to Johns Hopkins Medical’s researchers, they have discovered how a mind cell surface molecule influences the behavior of some cells.
The research, published October 2 in , Nature, reveals how a molecule, the calcium permeable ( CP ) -AMPA receptor, suppresses a specific neuron’s ability to pay attention to specific external cues, such as your friend’s earrings, according to the study in genetically-engineered mice.
Understanding why some neurons are less” selective” about how to respond to particular cues may also be useful for researchers studying disorders like schizophrenia, seizures, and dementia, which are both caused by defective brain function and misfiring in the vertebrate brain.
” We’ve discovered that the calcium breathable type of AMPA synapses has an added responsibility of suppressing the sensitivity of a given neuron”, says , Ingie Hong, Ph. D.,  , earliest writer and an instructor in science at the Johns Hopkins University Medicine.
The part of these particular receptors in the wider vertebrate head as it functions in daily life has remained a secret up until now.
Along with Hong, the study was led by , Richard Huganir, Ph. Dr., who has been conducting research on AMPA receptor for more than 40 years, is the chairman of the Solomon H. Snyder Department of Neuroscience at the Johns Hopkins University School of Medicine.
The rapid transfer of information and storage creation in the brain, as well as the ability to recognize and recall a person’s name, are ascribed to AMPA receptors. The subtype of AMPA receptors in this study, CP-AMPA receptors, act as a “gate” that lowers the selectivity of parvalbumin ( PV ) neurons, which are inhibitory and thereby cast unselective inhibition to nearby neurons, the researchers say.
” Selective cells will react to something really precise, for example, your grandfather’s beard, whereas less choosy cells will respond to different encounters or individuals as well”, Hong says.
” We’ve been looking for the mechanisms and substances that control this precision, or selectivity, and how it goes astray in problems such as autism and epilepsy, where activating cells can become overtired”.  ,  ,
The researchers also found that variants of GluA2, a protein component within the CP-AMPA sensor, are associated with philosophical disability.
” People abnormalities in the GluA2 component of the AMPA synapses, which regulates the calcium absorption of the sensor, can lead to intellectual illness and autism”, says senior writer Huganir. This suggests that the AMPA receptor’s calcium permeability must be tightly controlled for human cognition.
Specifically, the investigators focused on CP-AMPA receptors in two distinct areas of the brain, the visual cortex, where neurons process visual information, and the hippocampus, where neurons respond to “where you are, where you are headed, or where you have been”, Hong says.
The researchers created novel adeno-associated virus vectors to replace calcium-permeable AMPA receptors with impermeable counterparts and express them in the mouse brain in order to conduct their research. They claim they hope that these vectors will aid in the treatment of future disorders brought on by AMPA receptor mutations.
The scientists used advanced imaging techniques to observe neuron structure and activity deep within genetically modified mice’s brains while videoing them to determine PV neuron selectivity.
” In most cases, we found that these PV neurons, which are typically less selective, became more selective to visual stimuli as well as spatial location when we swapped out CP-AMPA receptors for impermeable molecules, making inhibitory neurons act more like excitatory neurons”, Hong says.
The researchers claim that PV neurons have a high level of CP-AMPA receptors that are well preserved across a number of species of mammals, including humans.
According to Hong, “making neuron inhibition less selective makes our neural circuits more effective than those of non-neuropaths.” It “probably also implies that our neural networks are more stable.”
According to Hong, the new findings may have an impact on the use of artificial intelligence machine learning.
” In machine learning, there are many computerized’ artificial’ neurons that are trained to be very selective or less selective”, he says. We’re attempting to determine how specific and less specific units can collaborate to produce smarter AI and machines.
The scientists intend to investigate additional crucial molecules that have the ability to affect cognition.
A better understanding of brain molecules that play a role in biased neuronal computations in patients could, according to Hong, help advance the development of novel drug therapeutic targets for psychiatric disorders with a genetic component.
In addition to Hong and Huganir, other scientists who contributed to this study are Juhyun Kim, Dong Won Kim, Richard C. Johnson, Nathachit Limjunyawong, Zhuonan Yang, David Cheon, Taeyoung Hwang, Amit Agarwal, Xinzhong Dong, Seth Blackshaw, Dwight E. Bergles and Solange P. Brown of Johns Hopkins, Thomas Hainmueller, Thibault Cholvin and Marlene Bartos of University of Freiburg, Joram Keijser and Henning Sprekeler of Technical University of Berlin, Soo Hyun Park and David A. Leopold of the National Institute of Mental Health, Fenna M. Krienen of Princeton University, and Steven A. McCarroll of Harvard Medical School.
Funding: Funding for this research was provided by National Institutes of Health grants R37NS036715 and U01DA056556.
About this news about sensory neuroscience research
Author: Alexandra Carolan
Source: Johns Hopkins Medicine
Contact: Alexandra Carolan – Johns Hopkins Medicine
Image: The image is credited to David Cheon and Ingie Hong
Original Research: Open access.
” Calcium-permeable AMPA receptors govern PV neuron feature selectivity” by Ingie Hong et al. Nature
Abstract
Calcium-permeable AMPA receptors govern PV neuron feature selectivity
The brain creates internal representations of the outside world to aid in our survival. Excitatory cortical neurons are frequently tuned precisely to particular external stimuli. However, inhibitory neurons, such as parvalbumin-positive ( PV ) interneurons, are generally less selective.
PV interneurons differ from excitatory neurons in their neurotransmitter receptor subtypes, including AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid ) receptors ( AMPARs ).
Excitatory neurons express calcium-impermeable AMPARs that contain the GluA2 subunit ( encoded by , GRIA2 ), whereas PV interneurons express receptors that lack the GluA2 subunit and are calcium-permeable ( CP-AMPARs ).
We show that there is a link between the low feature selectivity of PV interneurons and CP-AMPAR expression.
We find low expression stoichiometry of , GRIA2 , mRNA relative to other subunits in PV interneurons that is conserved across ferrets, rodents, marmosets and humans, and causes abundant CP-AMPAR expression. CP-AMPARs in PV interneurons were replaced with calcium-impermeable AMPARs, which increased their orientation selectivity in the visual cortex.
This increase was cell-autonomous and could occur with changes beyond development, according to experiments to induce sparse CP-AMPAR expression.
Notably, CP-AMPAR removal did not alter excitatory–PV interneuron connectivity rates or unitary synaptic strength, which suggested that PV interneurons ‘ selectivity could be altered without significantly altering connectivity.
In , Gria2-knockout mice, in which all AMPARs are calcium-permeable, excitatory neurons showed significantly degraded orientation selectivity, which suggested that CP-AMPARs are sufficient to drive lower selectivity regardless of cell type.
Moreover, hippocampal PV interneurons, which usually exhibit low spatial tuning, became more spatially selective after removing CP-AMPARs, which indicated that CP-AMPARs suppress the feature selectivity of PV interneurons independent of modality.
These findings implicate a novel molecular mechanism that distinguishes this cell type in the neocortex and reveal a new role for CP-AMPARs in maintaining low-selectivity sensory representation in PV interneurons.
