In the beginning: the founding of the Society for Claustrum Research

As the legend goes, in the 1960s a group of researchers across a multitude of disciplines recognized the emergence of a new field of science. New advances and techniques were allowing investigators to at long last peer inside the black box of the mind: the brain. Disgruntled at being labeled as no different from psychologists (who at the time were still shrouded by the tall shadow of Freud), these scientists did what most disgruntled scientists do and got together for a beer to commiserate and make a plan of action. By 1969, twenty of these brain-scientists met in the National Academy of Sciences building in Washington DC and the Society for Neuroscience (SfN) was born. Attendance at the first meeting in 1971 was just over 1,000 scientists, all coming together for the first time to share their cutting edge work in this exciting, new field of study. By the end of the 1970s, this number had skyrocketed to 6,000 attendees. At last year’s 2014 meeting of the Society for Neuroscience in Washington DC, there were 30,000 students, postdocs, professors, vendors, press, etc. SfN had come of age.

On a cold Sunday night during that 2014 SfN meeting, a small group of neuroscientists met at a pub down the street from the convention center for an organizational meeting. The topic of the meeting was a small brain region known as the claustrum. Though only 40 people in attendance, the meeting had a vibrant energy and somehow seemed already nostalgic. There was a sense of historicity.

The claustrum is a small brain region found just beneath the cerebral cortex. In a recent NeuWriteSD post, Cailey Bromer wrote a wonderful piece on this brain region’s mysterious function and the lore surrounding it. As the story goes, the famous co-discoverer of DNA and former director of the Salk Institute, Francis Crick, became convinced in his later career that the claustrum may be the key to understanding many mysteries of brain function, including consciousness [1]. In a now seminal paper on the topic entitled “What is the function of the claustrum”, Crick and his long time co-author Christof Koch (now the President and Chief Science Officer of the Allen Brain Institute in Seattle) posited that the claustrum, owing to its unique, widespread connectivity, may be the conductor of the orchestra that is the brain, coordinating many disparate regions of the cerebral cortex into a unified harmony of consciousness [2]. Crick was so fascinated by this brain region that he spent his final hours of life revising his manuscript, with the hair-raising phrase at the end of the article saying, “What could be more important? So why wait?”

As one might gather from the small attendance (40 people) at that first organizational meeting of the fledgling claustrum society, the field of neuroscience has largely ignored this brain region. Searching through titles and abstracts of all scientific papers in the NIH’s catalogue, one finds the claustrum is vastly under-represented in the literature. Other small brain regions show papers numbering in the tens of thousands (thalamus = 28,837 papers; hippocampus = 82,734 papers), whereas the claustrum has yet to reach a thousand (claustrum = 990). For this reason, 40 neuroscientists, myself included, met at that pub in Washington DC and the Society for Claustrum Research (SfCR) was born.

On October 19th of this year, our small group stopped waiting (as Crick would say) and the SfCR held its first official satellite meeting at the 2015 Society for Neuroscience conference in Chicago. We were honored to have Crick’s co-author, Christof Koch, in attendance as the keynote speaker. He began his address by recounting in his own words the story of writing that last paper with Francis (as he refers to him), and describing the fervent passion Crick maintained about the work right up to his final breath.

Dr. Koch went on to relate a brief review of the claustrum and the work he found the most informative on the topic. Specifically, what interests Koch and other neuroscientists about the claustrum is its abnormal, tortuous shape compared to other brain regions (the claustrum is a thin sheet stretching from the front of the brain to the back, instead of being packed into one place like most other brain regions), and its extensive connectivity with the entire cerebral cortex. But perhaps most striking is the recent report that the claustrum is critically involved in the emergence of consciousness, and electrically stimulating the claustrum region can “turn off” consciousness.

Following his review of the claustrum, Dr. Koch went on to describe exciting new research at the Allen Institute for Brain Science, where researchers are using cutting edge viral tracing techniques in genetically engineered mice to reveal the connections of the claustrum. Like any electric circuit, the first step towards understanding its function is to draw the wiring diagram, showing how each resistor, transistor, etc. are connected. Though not the first to do this for the claustrum, the work being done at the Allen Institute represents the most advanced attempt to draw the wiring diagram of the claustrum in mice to date.

Lastly, Dr. Koch presented data from his fellow researchers at the Allen Institute who have recently characterized the gene expression in the claustrum of humans, and identified the protein “vesicular glutamate transporter 3 (vGluT3), as being uniquely expressed in the claustrum compared to the other tissue within the central nervous system. This finding is an important step towards identifying what makes the claustrum different from other brain regions, and allowing future research to explore the role of vGluT3 in unraveling the function of the claustrum.

Presentation by Christof Koch at SfCR 2015. Image by ©Jared B. Smith

Presentation by Christof Koch at SfCR 2015. Image by ©Jared B. Smith

Following Koch’s address were five short talks on the cutting edge of claustrum research. These talks included new investigations into claustrum function using all the recent miraculous techniques of 21st century neuroscience. One study used resting state functional magnetic resonance imaging to demonstrate that the claustrum is part of a circuit with medial prefrontal cortex (involved in higher order, cognitive processes) and mediodorsal thalamus (also know to be involved in cognition), which is synchronized in the awake state but becomes desynchronized under anesthesia. This study is the first to show what brain regions the claustrum is connected to that support consciousness. Another fascinating study used voltage sensitive dye imaging to show how information travels throughout the entire claustrum (from the front of the brain to the back), along a unique set of internal fibers that interconnect the claustrum with itself [3], a very rare property in the brain. Other talks discussed in vitro electrophysiology in genetic mouse lines, a method used to tease apart local neuronal microcircuitry within the claustrum. The final presentation discussed a theoretical framework of the claustrum’s involvement in altered states of consciousness, including hallucinatory episodes in response to drugs such as salvia [4]. These presentations promoted wonderful conversations amongst attendees and inspired budding collaborations.

Additional exciting news discussed at the SfCR meeting was the founding of a journal dedicated to the claustrum. Aptly named “Claustrum”, this new journal was pioneered by Dr. Lawrence Edelstein, a long time researcher of the claustrum. Dr. Edelstein has also been heavily involved with organizing the SfCR, in addition to editing the first ever book on the claustrum with John Smythies and Vilayanur Ramachandran of UCSD.

In the 1960s the brain was as mysterious as ever, but owing to a dedicated group of pioneering scientists, the Society for Neuroscience was formed to push the field forward onto the sea of discovery. Nearly 50 years later, our progress has been astounding, from discovering the brain’s GPS system to controlling brains with light. Not only are neuroscientists discovering the secrets of the brain, but we are learning how to manipulate them, to hopefully someday treat a wide variety of neurological disorders.

Now as we turn our eyes to new horizons, the Society for Claustrum Research’s goal is to remind us all that we still do not know the function of a rather sizeable part of the human brain: the claustrum. Though the SfCR is small now, our passion is immense, and we hope that 50 years from now we can look back at that photo of 40 people and say our dreams of grandiosity came to fruition. However, such dreams for the future rest in the enthusiasm, curiosity and ingenuity of our future members. It is our sincerest hope that by raising awareness of this mysterious brain region, we will encourage others to apply their own research methods and lines of study to the claustrum, however applicable. So get involved! Follow us on social media, come to our annual meetings, and let’s see what exciting new discoveries you can contribute to this blossoming, young field of research.

As with all great explorations, it is now time for neuroscience to seek new, undiscovered countries, and the claustrum is ripe for picking. So why wait!

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[1] Stevens, C. (2004) Crick and the claustrum. Nature 435, 1040-1041.

[2] Crick, F.C. & Koch, C. (2005) What is the function of the claustrum? Phil. Trans. R.Soc. B 360, 1271-1279.

[3] Smith, J.B. & Alloway, K.D. (2010) Functional specificity of claustrum connections in the rat: interhemispheric communication between specific parts of motor cortex. J. Neurosci. 30(50):16832-16844.

[4] Stiefel KM, Merrifield A and Holcombe AO (2014) The claustrum’s proposed role in consciousness is supported by the effect and target localization of Salvia divinorum. Front. Integr. Neurosci. 8:20.