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This week we profile a recent publication in Cell from Dr. Adam Cohen‘s laboratory (Pictured) at Harvard University.

Can you provide a brief overview of your lab’s current research focus?

We develop physical tools to study molecules, cells, and organisms.  Much of our research focuses on studying bioelectrical phenomena, trying to understand the roles of electrical signaling in the nervous system and also in other tissues throughout the body.  We’ve developed sophisticated tools for imaging very fast voltage dynamics inside of living animals.

What is the significance of the findings in this publication?

We studied how the top layer of the brain’s cortex (Layer 1) transforms sensory inputs to outputs.  Layer 1 is thought to play an important role in regulating whether the underlying cortical layers process or ignore sensory inputs, i.e. in modulating attention.  What attributes of a sensory input make it worthy of attention?  We used new voltage imaging and optogenetic techniques to show how the Layer 1 circuit acts as a filter for novel or salient inputs, and how modulatory inputs from other brain regions can adjust the sensitivity of the Layer 1 filters.  These experiments give an intuitive picture for how this critical brain region responds to sensory inputs.  The experiments also make several testable predictions for how sensory and modulatory inputs should combine in Layer 1.

What are the next steps for this research?

As part of the project, we built a computational model of cortical Layer 1 which made several surprising predictions.  There’s a century-old finding in psychology called the Yerkes-Dodson Law which states that as arousal increases, performance on a task first increases and then decreases (this is familiar to anybody who has ever ‘frozen up’ in the last five minutes of a test).  A surprising prediction of our model was that the sensitivity of cortical Layer 1 to sensory inputs would show a similar inverted-U dependence on neuromodulatory inputs that signify arousal.  We’re really interested to explore whether this Layer 1 circuit could contribute to the neural mechanisms underlying the Yerkes-Dodson Law. More broadly, we’re also continuing to work on improving the voltage imaging tools.  This includes developing molecular reporters and microscopes to image deeper in the brain, over more cells, and with better sensitivity.

If you’d like us to mention your funding sources, please list them.
This work was supported by the NIH and the Howard Hughes Medical Institute.


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