Neuroscience news block: mysterious giant neurons, neurobiology of being fun and LSD potency explained.

Neuroscientists did not sit idly by in the past month: while you were going about your business they discovered a giant neuron wrapping itself around the entire mouse brain, recognised the differences between experienced improv comedians and newbies struggling to be funny (apart from the obvious joke quality) and took the first ever 3D image of LSD bound to a brain receptor.

Let’s start with the news from everyone’s favourite field of psychedelic research. Scientists think they have managed to identify the secret behind LSD’s potency 1 (LSD can send you over the moon for up to 18 hours, whereas, for example, DMT, another potent psychedelic substance, only allows for a 15 minute trip). In order to get to the bottom of it, the researchers decided to investigate the behavior of LSD on the molecular level. First of all, they waited for an LSD molecule to bind itself to a brain serotonin receptor and then they froze it in a form of a crystal. Then, they took a 3D X-ray image of it. And this snapshot is where they saw something unusual: normally drugs (and other molecules) come and go from the receptors in a way cars drive in and out of the garage; when LSD bound itself to the receptor, however, it sort of folded one part of the receptor over itself like a lid. It looked like the lid basically trapped the molecule inside of the receptor making it work on that psychedelic experience with no breaks. As receptor proteins are constantly wiggling around it is likely that eventually the lid flops open setting the molecule free. When the scientists created a mutant receptor with a much floppier lid they saw that LSD bound and detached much quicker and that this shorter binding induced different signaling changes in the neuron. As psychedelics have some promising potential for treating such things as anxiety, depression and addiction, solving LSD’s way of action can help us adjust it to show beneficial effects without sending people to the sky with diamonds, design better medication and adjust existing drugs.

A molecule of LSD bound to a serotonin receptor. The orange stick in the middle is the "lid" keeping it trapped. Credit: Lab of Bryan Roth, UNC School of Medicine

A molecule of LSD bound to a serotonin receptor. The orange stick in the middle is the "lid" keeping it trapped. Credit: Lab of Bryan Roth, UNC School of Medicine

In other news, scientists have recently found something unusual in the brain. Like an ivy plant wrapping itself around a tree a giant neuron appears to be enclosing the entire mouse brain2. It connects to pretty much every outer area in both hemispheres, resembling an electrical wire providing a whole city with electricity. Moreover, two more giant neurons that branch extensively throughout the brain were found to stem from the same brain region as the first one. This region they originate from is called the claustrum, a very thin sheet of cells which coincidentally is one of the best-connected regions of the brain. It helps us to perform such higher cognitive functions as long-term planning. Previously, claustrum has been shown to have some connection to consciousness (e.g., its electrical stimulation led to switching the consciousness on and off in an abrupt way3 and its damage was correlated with the duration of loss of consciousness4). One of the main author of the present study has suggested earlier that the claustrum is acting like a conductor of an orchestra, combining all of our internal and external perceptions into one unifying experiences. Continuing this line of reasoning, he sees these giant neurons connecting to everything as evidence for claustrum’s role in consciousness. The researchers plan to continue mapping neurons originating from claustrum to see whether all of them extend throughout the whole brain or whether they differ project to slightly different areas. While it is surely interesting to discover neurons looking like they act as a powerful switch to conscious behavior it is better to hold the horses with sensationalist stuff like “SEAT OF CONSCIOUSNESS IS FOUND OMG11!”. It is a far way before we can transfer this findings to humans and, moreover, to decipher the computational mechanisms behind the wonder which is our consciousness.

Three giant neurons. The blue one is the giantest. Credit: Allen Institute for Brain Science

Three giant neurons. The blue one is the giantest. Credit: Allen Institute for Brain Science

In less existentially daunting news: it was identified how exactly Amy Poehler and Stephen Colbert differ from your drunk uncle telling racist jokes (and me writing this post). The researchers compared experienced improv comedians with amateur comics to see where in the brain does creativity of humour hide5. In order to do that the scientists scanned the participants while they were trying to come up with funny captions for New Yorker cartoons. Two regions were found to be active during the process of being funny -- medial prefrontal cortex (mPFC) and temporal association regions. However, their activation level differed depending on how experienced with comedy the participants were. Seasoned comedians showed much higher activation in their temporal region which is indicated in memory, semantic knowledge, merging information to complex contextual associations and recognizing language and objects we see. In contrast, newbies relied more heavily on their mPFC, an area responsible for such advanced cognitive functions as decision-making and planning. It seemed like the experience allowed the comedians to let go of the control and to let their free spontaneous associations guide them instead of deliberately and painstakingly coming up with a joke. The fun ratings for the captions were also higher the larger the activation in the temporal areas was. I was trying to go for a closing joke here but my temporal association areas failed me. Sorry.

Some good old improv for you.

And, finally, some short and sweet futuristic news. Scientists have managed to grow a brain out of your shed skin!... Almost. What they actually did was turning skin cells into a type of neural stem cells which then were able to produce new neurons.6 And unlike previous experiments working on the same thing they did it without genetic manipulation. This is important because it means it can be used to fight neurodegenerative diseases (along the lines of “just take some skin and replace all the nerve cells killed by Parkison’s!”) and that we can study genetic diseases of the nervous system in a dish -- skin cells turned neurons would carry the genetic mutation causing the disease, so that we won’t need to take actual neurons from a person.

Stay tuned for some neuroscience of sleep coming next!