The brain's balancing act: Researchers discover how neurons equalize between excitation and inhibition

The brain's balancing act
This fluorescent image shows excitatory neurons in green and inhibitory neurons in magenta. Credit: UC San Diego School of Medicine

Researchers at the University of California, San Diego School of Medicine have discovered a fundamental mechanism by which the brain maintains its internal balance. The mechanism, described in the June 22 advanced online publication of the journal Nature, involves the brain's most basic inner wiring and the processes that control whether a neuron relays information to other neurons or suppresses the transmission of information.

Specifically, the scientists have shown that there is a constant ratio between the total amount of pro-firing stimulation that a neuron receives from the hundreds or thousands of excitatory neurons that feed into it, and the total amount of red-light stop signaling that it receives from the equally numerous inhibitory neurons.

This constant ratio, called the E/I ration, was known to exist for at a given time. This study goes a step further and shows that the E/I ratio is constant across multiple neurons in the cortex of mice and likely also humans, since the fundamental architecture of mammalian brains is highly conserved across species.

"Neurons in our brain drive by pushing the brake and the accelerator at the same time," said Massimo Scanziani, PhD, professor of neurosciences, Howard Hughes Medical Institute investigator and co-author. "This means that there is no stimulus that you can apply that will activate purely excitatory neurons or purely inhibitory ones."

"There is always a tug-of-war. It's weird but very clever. It allows the brain to exert very subtle control on our response to stimuli." For example, Scanziani said it prevents both runaway neuronal firing (excitation) and permanent quiescence (inhibition) because excitation and inhibition are always coupled.

In experiments, the scientists also showed how the brain maintains a constant E/I ratio across neurons: The adjustment is carried out by the inhibitory neurons through the appropriate strengthening or weakening of . A synapse is the gap or juncture between two and synaptic strength refers to the degree to which a passed signal is amplified in the juncture.

"Our study shows that the are the master regulators that contact hundreds or thousands of cells and make sure that the inhibitory synapses at each of these contacts is matched to the different amounts of excitation that these cells are receiving," Scanziani explained. If, for example, the level of excitatory stimulation that a nerve cell is receiving is doubled, the inhibitory synapses over a period of a few days will also double their strength.

In terms of clinical applications, the scientists said that neurological diseases such as autism, epilepsy and schizophrenia are believed to be a problem, at least in part, of the brain's ability to maintain an optimal E/I ratio.

"If this E/I balance is broken, it completely alters your perception of the world," Scanziani said. "You will be less able to adjust and adapt appropriately to the range of stimulation in a normal day without being overwhelmed or completely oblivious, and E/I imbalances may be most easily noticed in social interactions because these interactions require such nuance and subtle adjusting."

Scientists have also proposed that some neurodegenerative diseases, such as Parkinson's and Huntington's disease, may be associated with a shift in the E/I balance.

Minghan Xue, a postdoctoral researcher in neurobiology and the study's lead author, said "now that we know how this E/I balance is regulated in a normal brain, we can begin to understand what goes wrong in the diseased state. It paves the way for interventions that might restore the balance in the brain."

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More information: Paper: Equalizing excitation–inhibition ratios across visual cortical neurons, DOI: 10.1038/nature13321
Journal information: Nature

Citation: The brain's balancing act: Researchers discover how neurons equalize between excitation and inhibition (2014, June 22) retrieved 23 October 2019 from
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Jun 22, 2014
See also: http://medicalxpr...ors.html

Taken together with this report, researchers seem to be getting much closer to understanding how the nutrient-dependent microRNA/messenger RNA balance determines cell type differentiation via amino acid substitutions, which are controlled by the metabolism of nutrients to species-specific pheromones that control the physiology of reproduction.

At the same time, serious scientists are distancing themselves from reports that mutation-initiated natural selection somehow results in the manifestations of biodiversity that are clearly linked from ecological variation to ecological adaptions in species from microbes to man via conserved molecular mechanisms (i.e., not by mutations).

Experience-dependent receptor-mediated changes in morphological and behavioral phenotypes are not likely to result from mutations that perturb protein folding.

Jun 22, 2014
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Jun 22, 2014
Re: "...the relationship between the cortex's two opposing forces is stabilized not only in time but also in space." from the article abstract at

Nutrient-dependent changes in the microRNA/messenger RNA (mRNA) balance appear to result in pheromone-controlled alternative splicings of pre-mRNA and amino acid substitutions that stabilize the DNA of organized genomes in species from microbes to man. The stability represents ecological adaptations that are also manifested in morphological and behavioral phenotypes and biodiversity attributed to ecological variation.

Attributing biodiversity to mutations, natural selection, and evolution has caused anyone who still believes in neo-Darwinian evolutionary theory to ignore the role of ecological variation and epigenetic effects of sensory input that link the epigenetic landscape to the physical landscape of DNA via conserved molecular mechanisms. Two generations of idiots is the result of that ignorance.

Jun 22, 2014
Their results integrate theoretical and experimental evidence that links sensory input to activity-dependent gene expression and to synaptic excitation and inhibition. Their insight into how two opposing synaptic inputs remain proportional in populations of differentiated cell types "...reveals an unanticipated degree of order in the distribution of synaptic strengths in cortical space."

Therefore, anyone who believes that their brain evolved via an accumulated of mutations and natural selection may want to start planning what they will say when others also claim that idea and other ideas associated with neo-Darwinism are nothing more than pseudoscientific nonsense.

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