Peter Schiller of the Department of Brain and Cognitive Science at MIT has been selected to receive the Jay Pepose ’75 Award in Vision Sciences for 2011 from Brandeis University. Schiller is being honored for work on visual perception and neural control of guided eye movements. Schiller will visit Brandeis on March 14, 2011 to receive the award and to lecture on “Parallel Information Processing Channels Created in the Retina”. The lecture will be held at 4:00 pm in Gerstenzang 121. For more information about Dr. Schiller and the Pepose Award, please the story on Brandeis NOW.
Learning from unexpected events
January 31, 2011 By
Have you ever heard the phrase ‘the eyes are a window to the soul’? New research from Dr. Robert Sekuler’s Vision Lab suggests that the eyes may be a window to the brain as well. In an article published in this month’s issue of the Journal of Vision, Neuroscience grad student Jessica Maryott (PhD ’09) and Psychology grad student Abigail Noyce showed that as participants learn, their eye movements change in a way that lets scientists investigate how that learning takes place, specifically in response to unexpected events.
Participants in the study watched as a disk moved on a computer screen in a zig-zag path; they then reproduced its trajectory from memory. Each path was repeated several times, allowing the researchers to examine the learning process as participants became familiar with the pattern and more accurate at reproducing it. Researchers also measured participants’ eye movements as they watched the disk move, and examined learning-related changes in those as well. The results suggest that eye movements reflect the participant’s level of learning by actually predicting where the disk will be going next.
Sometimes, part of the disk’s path changed after several repetitions going in the opposite direction (a 180 degree change, shown in the green trace on the figure), without warning to the participant. This caused participants to make a prediction error: the actual motion of the disk no longer matched the pattern they had learned, but their eyes moved in the direction of the expected movement (positive velocity) until they were able to correct the error (this is when the green trace reverses velocity and goes below 0 in the figure). After such a prediction error, when the pattern appeared again, participants’ eye movements showed that the previous prediction error produced fast ‘one-shot’ learning, and participants now expected to see the new version of the path (shown in the blue trace, which goes in the new expected direction, 180 degrees from the old – thus showing a negative velocity). The researchers concluded that unexpected events (like the induced error) have high salience for learning. These results suggest that humans have a cognitive system which monitors how well sensory input matches predictions, and responds to errors with sudden, strong learning about the new situation.
Getting a Leg Up on Movement Disorders
January 23, 2011 By
Over 40 million people worldwide suffer from movement disorders, which are clinically defined as any type of affliction that affects the speed, fluency, ease, or quality of motion. The symptoms of these disorders can manifest in many different ways (the most common being tics, tremors, dystonia, and chorea), and treatment is still elusive for a large number of these often debilitating diseases. The past several decades, however, have seen enormous advances in our understanding of the genes and proteins underlying these conditions, and what remains to be determined is the way in which these molecules interact with each other to produce either normal or pathological locomotor patterns.
Scaffolding proteins have recently become a point of interest in the field of movement disorders. As their name implies, these proteins act as “scaffolds” to tether other proteins together, thus facilitating protein-protein interactions. It has long been thought that scaffolding protein dysfunction could disrupt the formation of protein complexes critical for the production normal locomotion, but evidence for such conjectures has remained elusive.
in a recent article in the journal GENETICS, Dr. Leslie Griffith’s lab at Brandeis University published work implicating one such scaffolding protein of the MAGUK family, known as CASK-b, in locomotor pathology. Using the fruit fly Drosophila melanogaster as a model system, researchers in the lab combined recently-developed genetic tools with cutting-edge computer behavior analysis software to demonstrate that knocking out this protein produces a complex motor deficit (see figure below). Furthermore, this deficit appears to stem from a loss of CASK-b in the central nervous system, suggesting it plays a role in higher-order regulation of motor output. Interestingly, both the major locomotor control center of the insect brain (known as the ellipsoid body), as well as the motor neurons which the locomotor control center regulates, do not appear to require this protein to produce normal locomotor patterns. This finding implies that a novel region or regions of the fly brain may be contributing to central locomotor control. Understanding both the specific mechanism through which this protein acts, as well as the underlying circuitry responsible for this deficit, could contribute largely to the field of movement disorders as a whole.
Another surprising finding to come out of this study was the discovery of an additional mRNA transcript that arises from an alternative promoter in the CASK locus. Although similar to CASK-b in many ways, this alternative protein is actually most homologous to another member of the same family in vertebrates, known as MPP1. MPP1, like most of its MAGUK cousins, is also a scaffolding protein that plays a vital role in bringing various proteins together into signaling complexes, thus providing more opportunities for complex interactions to take place. The Drosophila genome has many fewer MAGUK proteins than most mammalian genomes. This finding implies that through utilization of alternative start sites that generate multiple proteins, the fly can still end up with a wide array of subcellular interactions. It is this underlying diversity of molecular interactions that is thought to allow the fly to produce to a variety of unusually complex behaviors, such as courtship, aggression, flight, and in this case motor control.
What spontaneous neural activity reveals about the brain
January 7, 2011 By
You look at a photograph of a hiker in an alpine landscape. The hiker, her dog, the trees in the background, and the houses of a village in the distance are vividly reconstructed by your brain from the shades of light and color on the paper. The subjects of the picture are so distinct and clear that it is hard to see how difficult it was for your visual system to reconstruct it. A closer examination highlights some of the problems our brain has to overcome: The hiker in the foreground is higher and occupies a larger area than the houses and the trees in the background, yet you perceive her as being smaller. The dog is partially hidden by one of the legs of its master, yet you perceive it as a single animal, rather than two half-dogs. Theoretical models and psychological experiments led researchers to think that, in these examples and in countless other everyday situations, your brain makes use of an internal model of the world, built over a lifetime of experiences, to correctly interpret the image.
By analyzing the mathematical equivalents of the internal model, researchers in Jozsef Fiser’s lab in the Volen Center for Complex Systems at Brandeis and colleagues at Cambridge University (UK) deduce that, if the internal model works as hypothesized by theoreticians, traces of its functioning would be seen in neural activity recorded in complete darkness. Intuitively, an internal model would use its understanding of typical natural images to “fill-in” noisy and incomplete parts of a visual scene. As the brightness of an image is reduced, the visual system increasingly relies on prior expectations, until most of the neural activity is dominated by the internal model. This intuition is compatible with previous observations of neural data showing strong and coordinated activity in the visual system in the absence of visual stimulation, whose significance had remained unexplained.
Figure 1: The two panels show the distribution of all possible instantaneous activity patterns on 16 electrodes, in response to natural movies (M, x-axis) and during spontaneous activity in the dark (S, y-axis). Colors represent the number of electrodes detecting activity in each pattern, as shown in the legend on the left. In a young ferret, just after eye opening, the frequency with which the patterns occur is very different in the two conditions (left panel); instead, for an adult animal of about 4 months of age, the two distributions are very similar, as indicated by the patterns clustering around the diagonal.
In a paper published this week in Science, the authors analyzed neural activity in the primary visual cortex of ferrets watching natural scenes or artificial patterns, or just sitting in darkness. They found that, as predicted by the model, when the animal is in darkness the recorded patterns of neural activity closely resemble those recorded in response to natural visual scenes, but not those recorded in response to artificial stimuli. The fact that the similarity was specific to natural scenes indicates that the neural activity was due to the model’s expectations about the environment, and not to some other secondary effects. The authors repeated the measurements on animals at different stages of development, and found that the match of neural activity in the dark and in natural images was not present at birth, but rather gradually developed over the first four months of visual experience, as the internal model adapted to the statistics of the external world.
These results provide neural evidence for the internal models theorized by computational neuroscientists, and allow us to take a glance at the computations performed by the visual areas of the brain.
Neurons branch out: a role for Rem2
January 3, 2011 By
The development of the central nervous system involves a series of complex yet tightly-regulated processes, including the formation of synapses, the sites of communication between neurons, and the morphogenesis of the dendritic arbor, where the majority of synaptic contacts occur. Importantly, the misregulation of these processes is a hallmark of many neurodevelopmental disorders, including autism and mental retardation. However, the molecular mechanisms that underlie these structural and functional changes remain largely obscure.
The lab of Prof. Suzanne Paradis at Brandeis is working to identify and characterize molecules that regulate neural development in the rodent hippocampus. A recently accepted manuscript at Developmental Neurobiology by Brandeis Neurocience Ph.D. student Amy Ghiretti and Dr. Paradis uses RNAi in primary hippocampal cultures to identify novel roles for the GTPase Rem2 in several neurodevelopmental processes. The RNAi-mediated decrease of Rem2 leads to the formation of fewer excitatory synapses, and also results in increased dendritic complexity, suggesting that Rem2 functions normally to promote synapse formation and to inhibit dendritic branching. Additionally, the 
binding of Rem2 to the calcium-binding protein calmodulin was identified as a key interaction that distinguishes the signaling pathways through which Rem2 mediates synapse development and dendritic branching. Overall, this study identifies Rem2 as a novel regulator of several neurodevelopmental processes, and importantly, suggests that Rem2 regulates excitatory synapse development and dendritic morphology via separable and distinct signaling pathways.
Figure: Neurons in which Rem2 protein expression has been decreased by RNAi (top) show increased dendritic branching compared to control neurons (bottom), suggesting Rem2 acts to inhibit branching
Wingfield Receives 2010 Baltes Distinguished Research Achievement Award
November 30, 2010 By
Update; BrandeisNOW has a in-depth profile on Prof. Wingfield.
Professor Arthur Wingfield is the 2010 recipient of the Baltes Distinguished Research Achievement Award. The $5000 award, given annually by the Margaret M. and Paul B. Baltes Foundation and Division 20 (Adult Development and Aging) of the American Psychological Association (APA), recognizes outstanding contributions to our understanding of adult development and aging. As part of the award, Wingfield will deliver a keynote address at the next annual meeting of the APA.
The number of adults age 65 or older in the US is expected to grow from 35 million in the year 2000, to 70.3 million in 2030. Among this group, hearing loss is the third most prevalent chronic medical condition, exceeded only by arthritis and hypertension. The hearing loss associated with adult aging, or presbycusis (literally, “old hearing”) presents a more complex picture than many realize. Whether the loss is mild or more severe, the source is a thinning of hair cells located in the cochlea, a spiral-shaped structure about only the size of the nail on your little finger. There are also “higher level” effects that include the pathways from the cochea to the brain, and age-related changes in the auditory receiving areas of the brain itself. These biological changes result in the older listener expending attentional effort that is not only tiring, but can draw on resources that would ordinarily be available for encoding what has been heard in memory.
This recent award recognizes Wingfield and his Brandeis colleagues’ contributions to understanding this complex interaction between sensory and cognitive changes in adult aging. Arthur Wingfield is the Nancy Lurie Marks Professor of Neuroscience and director of the Volen National Center for Complex Systems at Brandeis. His work has also been recognized by the American Speech, Language and Hearing Association, and two successive MERIT Awards from the NIH’s National Institute on Aging.
