When Brain and Behavior Picture Together

Published in Lab Times 01-2010.

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The plasticity of the brain allows for structural changes that suit individual behavior and lifestyle. Using MR imaging, Annemie’s group has recently discovered that the brain of a songbird gets geared up for the breeding season in more ways than just one. Is there something more to their images?

The clichéd expression “men are from Mars and women from Venus” stems from the notion that behavioral differences exist between the two sexes; while men have an eye for quantity, numbers and logic and are better at performing one task at a time, women think in terms of quality and utility and have an edge over the other gender in efficiently handling multiple tasks all at once.  I do not wish to spur a hornet’s nest here with a gender debate but I wish to turn your focus to the very many behavioural differences that exist between individuals within any species. Recent research, actuated by the use of powerful imaging techniques has elucidated that such differences in the characteristics of individuals, not limited by gender, in fact, relate to subtle variations in the structural intricacies of the brain. In an interesting study in London (courtesy: Cold Spring Harbor Laboratory), taxi drivers were found to have large hippocampi, the center for spatial learning, as they sat on end driving long distances and the size of their hippocampus did actually correlate with the length of their career!

On one hand, the brain orchestrates behavior and on the other, it is in turn, influenced by behavior, social status and the immediate environment of an individual. This “interactive process” thus establishes an interdependence of the brain structure and the behaviour of an organism. The ‘neuroplasticity’ of the brain has acquired great attention with the development of smart imaging tools such as magnetic resonance imaging (MRI) including blood-oxygen level dependent functional MRI (BOLD fMRI) and diffusion tensor imaging (DTI) among others.

Prof. Annemie Van der Linden and her Bio-imaging lab at the University of Antwerp, Belgium have been pursuing an exciting study on behavior-modulated structural changes in the rodent, avian and fish brain with their imaging expertise for over two decades. Their recent moment of Eureka revealed a striking correlation between the ultra-structural features of the auditory forebrain of the songbird (Sturnus vulgaris) and its socio-sexual behaviour with the on-coming breeding season.

Gaining a foothold with MRI

With their Bio-imaging lab centered on MRI, Annemie and her colleagues have been addressing major questions in neuroplasticity as well as investigating various aspects of neurodegeneration and regeneration among others, in rodents, birds and fish all of which have a size appropriate for imaging. As a non-invasive in vivo technique, MRI has come handy for their study of structural changes in the brain. “In contrast to conventional histological and electrophysiological methods, MRI does not limit analyses to some sections or regions of the brain, instead it allows for a comprehensive research of the entire brain”, elucidates Annemie as she introduces the ‘asset’ of her lab. In imaging structural changes in the brain, be it reversible, arising from seasonal changes, or irreversible, associated with progression of disease in pathological conditions, MRI out-performs in vitro approaches. The latter have the major shortcoming that they produce data collected from several individuals and do not account for inter-animal variations. With MRI, it is possible to perform longitudinal imaging in the same subject to study periodical changes in the brain structure or to trace back to older images of the healthy animal during the prognosis of a disease. The lab also performs diffusion tensor imaging (DTI) to obtain data on the directionality of diffusion of water molecules which is characteristic of the local ‘micro-architecture’ of the brain.

“The only limitation with imaging”, Annemie prompts, “is that the information you get is a correlate of a set of several features or events in the brain”. The molecular mechanism underlying a particular observation is only implied and not lucid. “A change in DTI, for example, could mean anything like axonal loss or demyelination and this speculation requires validation using other approaches”, she completes.

Choice of species is critical

Even within the optimum size range of animals of up to 8 cm diameter for sharp imaging, Annemie’s group resort to a variety of species for their experiments. Annemie believes in comparative neuroscience and ascertains that the choice of species is crucial and one must pick the best model to address every specific scientific question. “For example, the rodent brain is a good model for stroke while the fish brain can cope with anoxia and hypoxia and is well-suited for studies on the response of the brain to changes in oxygen levels. Likewise, the songbird brain serves as a classic model for extreme structural plasticity”, she elaborates. The interdependence of brain and behaviour is best elucidated in the songbird brain. The changes in the structural characteristics of the latter are intertwined with seasonal changes when the bird behaviour is modified and the readout of this behavioural change is that the bird starts to sing. With the onset of the breeding season (spring), neuronal plasticity of the songbird brain becomes more conspicuous. It is then that the song becomes highly sexually-motivated and this change in singing behavior is exactly encoded by structural changes in the brain, particularly within the song control system (SCS).

In their recent paper, the Bio-imaging group has identified for the first time, structural changes in the auditory fore-brain of the songbird that complement bird behavior and seasonal changes. Annemie agrees that bird imaging is challenging though undoubtedly rewarding. Firstly, one is faced with the problem of massive artefacts on the images that arise from air cavities in the skull. Another drawback with birds is the unfavourable surface-volume ratio that is prone to quick body-heat dissipation during imaging. Thirdly, controlling respiration by ventilation of birds could be highly invasive. However, with years of experience in imaging, Annemie and colleagues have their own way out of these difficulties and use additional tools such as DTI and contrast imaging to derive their theories on the plasticity of the bird brain.

The latest breakthrough

In their paper late last year (J.Neurosci. vol.29(43):13557-65), the Bio-imaging group published a profound characterization of the structural changes in the songbird brain at the onset of the breeding season. To start off, they obtained a series of brain images of a flock of songbirds in spring (breeding season) and of the same set of birds in summer (non-breeding season). They then arrived at an average spring brain and an average summer brain image, super-imposed the images, chose a number of regions of interest (ROIs) within and outside the SCS and evaluated the differences. They observed an overall decrease in the volume of telencephalon from spring to summer and to their surprise, they found statistically significant differences in regions not belonging to the SCS. After careful re-consideration of their images, they made the groundbreaking conclusion that it is in fact the secondary auditory region, the caudomedial nidopallium (NCM) and a few other regions of the social behaviour network (SBN) that exhibit a significant seasonal change.

This result was the first of its kind since it identified a DTI parameter that correlated with seasonal differences in exactly those regions of the SBN which have been reported to have a high aromatase activity in homologs. Aromatase activity has been shown to peak in the breeding season in canaries and induce neuronal branching and nuclear enlargement thereby influencing diffusion characteristics of water in these tissues. Thus, the group could show that the DTI parameter actually reported seasonal changes in aromatase activity, a cellular attribute, in the SBN. Their work opens new portals to the application of imaging tools in speculating, with greater precision, cellular properties. It also sheds light on the involvement of multiple senses in the songbird’s singing behaviour across seasons.

Manifold implications

Annemie and colleagues are now convinced that neuronal plasticity in the songbird is not exclusive to the SCS and it is essential that further research takes a broadened view on the plasticity of the brain. A study of the seasonal impact on cognition in birds in terms of song learning, song discrimination and recognition memory is on their list of to-do’s. While all this is part of the bird team’s agenda, the lab also has a rodent team that will continue to focus on neurodegeneration to develop early diagnostic readouts using their favourite imaging instrument. With the possibility of relating to cellular attributes with MRI, as the group just discovered, their work now holds major implications in gaining valuable medical insights.

As a full professor of Biology, Annemie has adopted an interdisciplinary approach to address her scientific questions and her team has expertise not only in Biology but also in Physics and Engineering. Their research is supported by the University of Antwerp, European grants and by the National Research Foundation (FWO), Belgium. The one thing that amuses Annemie and keeps her strongly inclined to Science is, “how Nature uses evolution to solve problems an organism is confronted with”. And as organisms evolve, there’s all the more reason to take on comparative research.

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