Article of the Month, October 2018 (London's lab)

October 15, 2018

Adrenergic Modulation Regulates the Dentiric Excitability of Layer 5 Pyramidal Neurons In Vivo 


Authors:  Christina Labarrera, Yair Deitcher, Amir Dudai, Benjamin Weiner, Adi Kaduri Amichai, Neta Zylbermann, Michael London


Published in Cell Reports on April 2018  

Single neuron




Many studies have shown that some of the power of the brain comes from its ability to combine information from many sources. For example, what we see when we watch a movie, can be greatly affected by our memories, and what we sense when we touch an object can be affected by what we hear. A possible mechanism to achieve this remarkable ability is an important property of specific type of neurons in our brain. These neurons are called pyramidal neurons of layer 5 and are unique in that they collect information from two main sources. In one part of the neuron (known as the basal dendrites) the neuron collects information from its local neuronal network, information that is typically limited to a specific type (e.g. only visual information). However, on a different region of the neuron (known as the apical tuft) information arrives from all over the brain and is very broad in nature. Thus, pyramidal neurons from layer 5 can serve as integrators that process specific information (e.g. visual) within a broad context. But our experience tells us that there are times when we would like to "lower the volume" of the context (e.g. concentrate on the face of your partner in a loud party) while in other times we need to combine as much information as we can get (looking for a parking spot). How do we control this? Neuromodulation is a fundamental process by which a handful of brain derived chemicals called neuromodulators (such as Serotonin, Dopamine, Acetylcholine and Norepinephrine)  can profoundly alter the behavior of neural systems and consequently the behavior of the organism. Norepinephrine plays key roles in many executive functions, such as attention and working memory, as well as in sensory processing. In the present study, using state of the art experimental techniques and sophisticated computer simulations we found that in pyramidal neurons, Norepinephrine has specific effect on the sensitivity of the apical tuft. We used a drug called guanfacine that mimics the effect of Norepinephrine (and is used to treat people with attention deficit disorder) and shown that it makes apical tuft more sensitive to incoming information. Therefore by changing the levels of Norepinephrine, the brain can control how much neurons “pay attention to the context”. These findings may have important implications for our understanding of how adrenergic neuromodulation affects attention and sheds light on the neuronal mechanism of drugs used to treat attention deficit disorder (ADD).


Link: https://www.sciencedirect.com/science/article/pii/S2211124718304790