New Imaging Techniques to Unlock Brain Disordersby Veronica Pamoukaghlian, MA | December 4, 2012
A study published in recent issue of Neuron describes a very promising new imaging technique, which has successfully charted complex neural reactions and could lead to the detection of brain activity patterns associated with certain psychiatric disorders, including autism and obsessive-compulsive disorder.
Neuroscientists have made some spectacular breakthroughs over the last decade. Imaging techniques have combined with complex cell-labelling methods to enable the visualization of events in living brain cells at both cellular and sub-cellular levels. The MIT-lead team´s contribution to brain imaging opens some new and exciting paths in the visual documentation of neural processing.
Using calcium ion recognition in the brains of genetically-engineered mice, a team of scientists from some of the top brain research institutes in the US was able to track the brain circuit activity that occurs in the brain when, for example, a certain smell is perceived. MIT has made a video relating these experiments available online.
One of the authors of the study, Guoping Feng, from the Stanley Center for Psychiatric Research, explains,
To understand psychiatric disorders we need to study animal models, and to find out what’s happening in the brain when the animal is behaving abnormally. This is a very powerful tool that will really help us understand animal models of these diseases and study how the brain functions normally and in a diseased state.
Basically, the electrical signals that neurons generate prompt an influx of calcium ions when a cell becomes active. The calcium is dyed, in order to make it visible through imaging. However, in the past, this method couldn´t be used to focus on specific kinds of cells, because the dye was absorbed by all of them alike.
The paper´s authors developed a new calcium-based imaging technique using a green fluorescent protein (GFP). Although similar techniques have been used before, one of the MIT team´s greatest breakthroughs has been the development of a new, improved type of green fluorescent protein, which is powerful enough to be used in living animals.
Once the new GFP was ready, genetically-engineered mice were used to track activity in pyramidal cells, and the scientists were able to identify activity in these neurons as a response to certain stimuli. For example, they tracked down activity following the touching of a mouse´s whiskers or the perception of certain smells.
The next step for the research team is the development of a new set of transgenic mice which they believe will allow them to compare activity in the brains of autistic and obsessive-compulsive individuals to that which occurs in the brains of normal mice.
According to Dr. Feng,
Right now, we only know that defects in neuron-neuron communications play a key role in psychiatric disorders. We do not know the exact nature of the defects and the specific cell types involved. If we knew what cell types are abnormal, we could find ways to correct abnormal firing patterns.
While the paper´s findings may appear far from spectacular to the non-informed observer, its implications for the future of brain imaging may well represent an unparalleled advancement for the understanding of psychiatric disorders at a neuronal level.
Chen Q, Cichon J, Wang W, Qiu L, Lee SJ, Campbell NR, Destefino N, Goard MJ, Fu Z, Yasuda R, Looger LL, Arenkiel BR, Gan WB, & Feng G (2012). Imaging Neural Activity Using Thy1-GCaMP Transgenic Mice. Neuron, 76 (2), 297-308 PMID: 23083733
Feng G, Mellor RH, Bernstein M, Keller-Peck C, Nguyen QT, Wallace M, Nerbonne JM, Lichtman JW, & Sanes JR (2000). Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron, 28 (1), 41-51 PMID: 11086982
Becker K, Jährling N, Saghafi S, Weiler R, & Dodt HU (2012). Chemical clearing and dehydration of GFP expressing mouse brains. PloS one, 7 (3) PMID: 22479475
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