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Scientists Discover ?Volume Control? for Connections between Brain Regions
29 Aug, 2007 12:59 pm
Nerve axons, the hair-like processes that connect brain regions, have been likened to telephone wires in that they faithfully relay information without altering it. However, a recent study shows that, contrary to previous thinking, the information being relayed may be increased or decreased by neurotransmitters (the brain?s own chemicals) or drugs such as nicotine. In other words, axons possess a ?volume control.? This finding may help us understand higher brain functions such as perception and cognition, and help devise treatments for diseases that disrupt connections among brain regions.
In the course of our studies on the auditory thalamo-cortical slice, we made a completely unexpected discovery about how brain cells work.
For years, scientists have known that information travels between brain cells along hair-like extensions called axons. Axons connect a brain cell’s main body, which receives inputs from other brain cells, to the synapse that relays its output. Information processing, it was thought, occurs only in the brain cell’s main body and synapse, but not in the intervening axon. Axons were thought to be like telephone wires that reliably convey signals from one phone to another. But, in our study we found that if you stimulate the axon, the signal can be altered, like giving the telephone wires a volume knob. Our experiment was made possible by having the auditory thalamo-cortical slice, which maintains intact the axons connecting the auditory thalamus and auditory cortex. Using the drug nicotine, we stimulated an axon to determine how it would effect a signal that a brain cell in the auditory thalamus was sending to the auditory cortex. Without applying nicotine, about 35 percent of the messages reached the cortex. But when nicotine was applied to the axon, the success rate nearly doubled to about 70 percent. This finding implies that there are proteins (receptors) on the axon that, in the live brain, must respond to the brain’s own neurotransmitters (chemicals that mediate communication between neurons). We confirmed this implication in the live mouse brain, which also shows that the finding didn’t only apply to brain slices in a dish.
The findings were published online August 19 in the journal Nature Neuroscience.
Our findings may help scientists develop treatments for psychiatric disorders such as depression and schizophrenia in which it is thought that different parts of the brain do not communicate properly with each other. Until now, scientists have thought that in the brain’s cortex – where most cognitive processes occur – information was processed only by the cell body, and not by its axon. The result of our study suggests that we must consider the axons as sites of information processing – and of potential problems when things go wrong.
Our research is funded by the National Institutes of Health (NIDA and NIDCD).
Kawai H., et al, Nicotinic control of axon excitability regulates thalamocortical transmission, Nature Neuroscience (19 Aug 2007)
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Thalamocortical connections are by far the most numerous in the brain, and it has long been known that they can be modulated by acetylcholine (ACh), but the mechanism(s) have been difficult to uncover. The authors studied both intact mice and living slices of mouse brains to provide evidence for a potentially novel means of action of cholinergic modulation in thalamocortical connections, with possible implications for how we sense and process environmental stimuli.
I accept the paper without any changes. The article is well-written and the content is of great interest.
This article is clearly written and simply explained. The authors make clear the advantages of using mouse slice preparations and use an appealing analogy to explain a complex point about neural transmission.
The paragraph beginning ?For years? contains the main point of the article. I would suggest adding a little more clarification. In particular, it might be helpful to spell out what?s novel here by directly contrasting the textbook roles of synapses vs axons in information transmission. That would bring the novelty of the authors? work clearly to the forefront before going on to read the methodological details. Otherwise, the central point might be missed until the final paragraph.
(1) ADHD is associated with fronto-cortical hypo-arousal (Barry, Clarke et al. 2003) and altered functioning of thalamo-cortical circuits (Sonuga-Barke 2005).
(2) It is known that there is a specific relationship between mothers? nicotine intake during pregnancy and ADHD development in the offspring (Zappitelli, Pinto et al. 2001), although the underlying mechanisms are not fully understood.
(3) Interestingly, nicotine was shown to reduce ADHD symptoms with a responder rate of 50% (placebo 6%) in a double-blind crossover clinical trial (Levin, Conners et al. 1996). It has been argued that nicotine might act on fronto-striatal dopamine re-uptake receptors in a similar fashion as methylphenidate (Krause, Dresel et al. 2003; Krause, Krause et al. 2006), a psycho-stimulant most commonly prescribed for the treatment of ADHD. The findings described by Kawai and colleagues suggest a potential alternative/additional mechanism for decreasing frontal hypo-arousal, that is by increasing axon excitability.
Thus, if nicotine enhances thalamo-cortical transmission and thereby influences sensory filtering and attentional focus, one might hypothesise that exposing the developing brain of a foetus to nicotine leads to alterations in this system. This might be examined by exposing pregnant mice to nicotine and investigating axon excitability in thalamo-cortical pathways, as well as bevavioural parameters as suggested by Sagvolden and colleagues (2005) in the offspring. If our hypothesis is correct, newborn mice should display decreased excitability compared to control mice. This might prove useful for the development of an animal model for an aetiological mechanism of ADHD, which should influence the understanding and the treatment of this disorder.
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Kawai, H., R. Lazar, et al. (2007). "Nicotinic control of axon excitability regulates thalamocortical transmission." Nat Neurosci 10(9): 1168-75.
Krause, J., K. H. Krause, et al. (2006). "ADHD in adolescence and adulthood, with a special focus on the dopamine transporter and nicotine." Dialogues Clin Neurosci 8(1): 29-36.
Krause, K. H., S. H. Dresel, et al. (2003). "The dopamine transporter and neuroimaging in attention deficit hyperactivity disorder." Neurosci Biobehav Rev 27(7): 605-13.
Levin, E. D., C. K. Conners, et al. (1996). "Nicotine effects on adults with attention-deficit/hyperactivity disorder." Psychopharmacology (Berl) 123(1): 55-63.
Sagvolden, T., V. A. Russell, et al. (2005). "Rodent models of attention-deficit/hyperactivity disorder." Biol Psychiatry 57(11): 1239-47.
Sonuga-Barke, E. J. (2005). "Causal models of attention-deficit/hyperactivity disorder: from common simple deficits to multiple developmental pathways." Biol Psychiatry 57(11): 1231-8.
Zappitelli, M., T. Pinto, et al. (2001). "Pre-, peri-, and postnatal trauma in subjects with attention-deficit hyperactivity disorder." Can J Psychiatry 46(6): 542-8.