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      "permlink": "giant-neurons-in-the-brain-may-play-similarly-giant-role-in-awareness-and-cognition",
      "title": "Giant neurons in the brain may play similarly giant role in awareness and cognition",
      "body": "<html> <p>https://cdn.steemitimages.com/DQmZcFzAVbP97QxZ1hLSX5coRvEAcRrANbEQfvS9876ViYf/image.png<em>Researchers believe that large cells called nucleus gigantocellularis neurons, pictured here, modulate blood flow by releasing nitric oxide.</em></p> <p>There is no shortage of wonders that our central nervous system produces -- from thought and language to movement to the five senses. All of those dazzling traits, however, depend on an underappreciated deep brain mechanism that Donald Pfaff, head of the Laboratory of Neurobiology and Behavior at The Rockefeller University, calls generalized arousal, or GA for short. GA is what wakes us up in the morning and keeps us aware and in touch with ourselves and our environment throughout our conscious hours.</p> <p><br></p> <blockquote>'It's so fundamental that we don't pay attention to it,' says Pfaff, 'and yet it's so important that we should.'</blockquote> <p><br></p> <p>Pfaff and his team of researchers certainly do. Now, in a series of experiments involving a particular type of brain cell, they have advanced our understanding of the roots of consciousness. Their work may potentially prove relevant in the study of some psychiatric diseases.</p> <p><br></p> <p><strong>The big cells in the black box</strong></p> <p><br></p> <p>The findings, published this month in Proceedings of the National Academy of Sciences, shed light on an area of the brainstem that is so little understood the first author of the paper, Inna Tabansky, a research associate in Pfaff's lab, calls it 'the black box.' That term is certainly simpler than its actual name -- the nucleus gigantocellularis (NGC), which is part of a structure called the medullary reticular formation.</p> <p><br></p> <p>In her work, using mice, Tabansky focused on a subtype of extremely large neurons in the NGC with links to virtually the entire nervous system, including the thalamus, where neurons can activate the entire cerebral cortex. 'If you just look at the morphology of NGC neurons, you know they're important,' Pfaff says. 'It's just a question of what they're important for. I think they're essential for the initiation of any behavior.'</p> <p><br></p> <p>To discover what role the NGC neurons might play in GA, Tabansky and her colleagues, including Joel Stern, a visiting professor in the Pfaff lab, began by identifying the genes that these neurons express. They used a technique known as 'retro-TRAP,' developed in the lab of Rockefeller scientist Jeffrey Friedman.</p> <p><br></p> <p>To Tabansky's surprise, the NGC neurons were found to express the gene for an enzyme, endothelial nitric oxide synthase (eNOS), which produces nitric oxide, which in turn relaxes blood vessels, increasing the flow of oxygenated blood to tissue. (No other neurons in the brain are known to produce eNOS.) They also discovered that the eNOS-expressing NGC neurons are located close to blood vessels.</p> <p><br></p> <p>In Pfaff's view, the neurons are so critical for the normal functions of the central nervous system that they have evolved the ability to control their own blood supply directly. ''We're pretty sure that if these neurons need more oxygen and glucose, they will release nitric oxide into these nearby blood vessels in order to get it,' he says.</p> <p><br></p> <p>The circumstances that would prompt such a response were the subject of further experiments. The scientists found evidence that changes in the environment, such as the introduction of novel scents, activated eNOS in the NGC neurons and produced increased amounts of nitric oxide in mice.</p> <p><br></p> <p>'There is some low level of production when the animal is in a familiar setting,' says Tabansky, 'which is what you expect as they maintain arousal. But it is vastly increased when the animal is adapting to a new environment.' This activation of the NGC neurons supports the case for their central role in arousal, Tabansky says.</p> <p><br></p> <p><strong>From cells to psychiatry</strong></p> <p><br></p> <p>Going forward, Tabansky says she's interested in exploring if their findings might help fill a gap in the understanding of certain disorders, such as bipolar disorder, suicidality, and ADHD. Some genetic research has implicated a role for the neurons she studied in these diseases, but the mechanism behind this link is not known.</p> <p><code>By showing that this gene and its associated pathways have a particular role, at least in the rodent brain, that relates to a fundamental function of the nervous system, is a hint about how this gene can cause psychiatric disease,' she says. 'It's very preliminary, and there is a lot more work to be done, but it potentially opens a new way to study how this gene can alter an individual's psychology.</code></p> </html>",
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      "body": "<html> <p>https://cdn.steemitimages.com/DQmRqiqiQvrqgkD9DzAEwTkK28isUmfQV9qYFfzz8L5MTEx/image.png</p> <p><br></p> <p>Can you tell the smell of a rose from the scent of a lilac? If so, you have your brain's piriform cortex to thank. Compared to many parts of the brain, the piriform cortex -- which lets animals and humans process information about smells -- looks like a messy jumble of connections between cells called neurons. Now, Salk Institute researchers have illuminated how the randomness of the piriform cortex is actually critical to how the brain distinguishes between similar odors.</p> <p><br></p> <p>'<em>The standard paradigm is that information in the brain is encoded by which cells are active, but that's not true for the olfactory system</em>,' says Charles Stevens, Distinguished Professor Emeritus in Salk's Molecular Neurobiology Laboratory and coauthor of the new work. 'In the olfactory system, it turns out it's not a matter of which cells are active, but how many cells are active and how active they are.'</p> <p><br></p> <p>Aside from better understanding how smells are processed, the new research, published in the Journal of Comparative Neurology on July 17, 2018, could also lead to greater insight into how some parts of the brain organize information.</p> <p><br></p> <p>When odorant molecules -- the signature of any given smell -- bind to the receptors in a person's nose, the signal is transmitted to the olfactory bulb, and from there to the piriform cortex. In other sensory systems -- like the visual system -- information maintains a strict order as it moves through the brain. Particular parts of the eye, for instance, always transmit information to specific parts of the visual cortex. But researchers have long known that this order is missing in the piriform cortex.</p> <p><br></p> <p>'<em>We haven't been able to discern any order in the piriform cortex connections in any species</em>,' says coauthor Shyam Srinivasan, an assistant project scientist at the <a href='http://www.kavlifoundation.org/'>University of California San Diego's Kavli Institute for Brain and Mind.</a> '<em>Any given odor lights up about 10 percent of neurons that seem to be scattered all over the piriform cortex</em>.'</p> <p><br></p> <p>To start working out the details of how the piriform cortex encodes odor information -- and whether its connections are truly random -- Stevens and Srinivasan analyzed the piriform cortices of nine mice using a variety of staining and microscopy techniques that let them visualize different cell types in the brain region. Their first goal: to quantify the number and density of cells in the piriform cortex.</p> <p><br></p> <blockquote>'This was really like a survey,' explains Srinivasan. 'We counted the cells in different representative areas and averaged them across the whole region.'</blockquote> <p><br></p> <p>The mouse piriform cortex, they concluded, has around half a million neurons in it, divided equally between the larger, less dense posterior piriform and the smaller, more dense anterior piriform.</p> <p><br></p> <p>Using this initial information on density and neuron number, as well as knowledge from previous studies on the number of neurons in the olfactory bulb and how many neuronal connections -- or synapses -- connect the olfactory bulb to the piriform cortex, the pair of researchers was able to draw a surprising finding: each neuron in the olfactory bulb is connected to nearly every single neuron in the piriform cortex.</p> <p><br></p> <p>'<em>Every cell in the piriform is getting information from essentially every odor receptor there is</em>,' says Stevens. '<em>There's not one 'coffee smell' neuron but a whole bunch of coffee cell neurons all over the place.</em>' Rather than a single receptor detecting one odor and lighting up one cluster of telltale neurons, he explains, each odor has a fingerprint that's based more on the strength of the connections -- while the smell of coffee may activate nearly the same neurons in the piriform cortex as the smell of chocolate, they'll activate each neuron to a different degree.</p> <p><br></p> <blockquote>'One advantage to this system is that it can encode very complex information,' says Srinivasan. 'It also makes it very robust to noise.' If one neuron sends a 'noisy' signal -- stronger or weaker activation than it should -- the noise gets cancelled out by the many other neurons sending simultaneous, more accurate signals.</blockquote> <p><br></p> <p>The researchers would like to repeat the work in other animals to see where similarities and differences lie. They also are interested in looking into other areas of the brain that have long been assumed to be dominated by seemingly random connections to see if they're organized in the same way.</p> <p><br></p> <p>Stevens and Srinivasan, who also had a paper come out in the <a href='http://www.jneurosci.org/'>Journal of Neuroscience</a> on July 13 about using the fruit fly olfactory learning circuit to improve the current crop of deep learning algorithms, were funded by the Kavli Institute for Brain and Mind at UC San Diego and the <a href='http://www.nsf.org/'>National Science Foundation.</a></p> </html>",
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