11 November 2010

In the Brain, Inhibition Sets Us Free

Our brains would not be able to function without inhibitory inter-neurons. The best description that I have read describing how interneurons control brain activity comes from Gyorgy Buzsaki's excellent book, "Rhythms of the Brain."

Scholarpedia presents a nice, brief description of inhibitory interneurons:
The importance of inhibition in the brain is aptly illustrated by the fact that in addition to excitatory principal cells, the brain contains diverse classes of specialized inhibitory interneurons that selectively innervate specific parts of the somatodendritic surfaces of principal cells and other interneurons. In the cortex, axon terminals of interneurons release gamma amino butyric acid (GABA) onto their synaptic targets, where the inhibitory action can compete with the excitatory forces brought about by the principal cells. However, inhibitory interneurons do much more than just provide stop signals for excitation. Proper dynamics in neuronal networks can only be maintained if the excitatory forces are counteracted by effective inhibitory forces. With only excitatory cells, it would be difficult to create form or order or secure some autonomy for transiently active groups, the hypothetical "cell assemblies", because in interconnected networks, excitation begets more excitation. Interneurons, by way of their inhibitory actions, provide the necessary autonomy and independence to neighboring principal cells. The functional diversity of principal cells can also be enhanced by the membrane domain-specific actions of GABAergic interneurons. Additionally, the opposing actions of excitation and inhibition often give rise to membrane and network oscillations which, in turn, provide temporal coordination of the messages conveyed by principal cells. _Scholarpedia

The image above and to the right illustrates a simple 2 neuron oscillator composed of an excitatory neuron and an inhibitory (inter) neuron. Input from the outside is always excitatory, and it is the turning on and off of the inhibitory neuron which accounts for the assembly's oscillation. The image below illustrates a 3 neuron oscillator, with the assembly on the left oscillating at 40 Hz and the assembly on the right oscillating at 30 Hz. The input from the NMDA neuron at the upper left determines which of the two oscillators is operating.
Image Source
Real neuronal assemblies in the brain are far more complex than these simple oscillators. But it helps to picture something simple before thinking about more complex and realistic assemblies -- which have a lot more things that can go wrong. Researchers at Baylor University have recently discovered a genetic variation that leads to dysfunction of inhibitory interneurons in Rett Syndrome -- a devastating neurologic disease of early childhood leading to severe problems of intellectual and motor development.
Children, mostly girls, born with Rett syndrome, appear normal at first, but stop or slow intellectual and motor development between three months and three years of age, losing speech, developing learning and gait problems. Some of their symptoms resemble those of autism.

These inhibitory (gamma-amino-butyric-acid [GABA]-ergic) neurons make up only 15 to 20 percent of the total number of neurons in the brain. Loss of MeCP2 causes a 30 to 40 percent reduction in the amount of GABA, the specific signaling chemical made by these neurons. This loss impairs how these neurons communicate with other neurons in the brain. These inhibitory neurons keep the brakes on the communication system, enabling proper transfer of information.

"In effect, the lack of MeCP2 impairs the GABAergic neurons that are key regulators governing the transfer of information in the brain," said Dr. Hsiao-Tuan Chao, an M.D./Ph.D student in Zoghbi's laboratory and first author of the report.

..."This study taught us that an alteration in the signal from GABAergic neurons is sufficient to produce features of autism and other neuropsychiatric disorders," said Zoghbi, a Howard Hughes Medical Institute investigator and director of the Jan and Dan Duncan Neurological Research Institute at Texas Children's Hospital. _SD
It does not require much interference in the normal operation of the molecular biology of the brain to cause severe dysfunction. The pathway of the dysfunction -- from molecule to synapse to cell assembly to developmental and behavioural dysfunction -- is intriguingly complex on many levels.

My main interest in this regard, is the transient long distance synchrony of cell assembly oscillatory activity in different parts of the brain. It would take several lifetimes to understand such phenomena in all their variation, origination, and modification. The implications of such understanding to human learning, creativity, health and disease, personality, and so on, are profound.

Inhibitory Interneurons and Network Oscillations

Some background reading on the phase-locking of neural populations via inhibitory interneurons PDF [Notice: Opening PDF documents can tie up a browser for several moments. If you think you want to download a PDF document, you may want to right click and select "save linked content as" option.]

Human Oscillatory Brain Activity near 40 Hz Correlates with Cognitive Temporal Binding PDF

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Blogger Christopher Willmot said...

Finding the whole field of neural oscillators befuddling, I can across this little ray of sunshine. I had already read the scholarpedia article. But having followed that very simple diagram at the top, the light dawned. Thank you.

Saturday, 19 January, 2013  

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