Neuroscience research highlights from SfN 2019

The Annual Society for Neuroscience (SfN) meeting features the latest discoveries in brain research, from the basic mechanisms, to translational and clinical studies. Here are some highlights from the conference.

This year,  the conference celebrated its 50th anniversary in the “Windy City”, Chicago, IL, USA. Unsurprisingly, this convention attracted close to 30,000 delegates around the workings of the brain “the universe between your ears” unassuming, but possibly, the most complex structure of the universe.

A zoo of brains

We must humbly acknowledge that much of what we know about the structure and function of the human brain today has been extrapolated from decades of studies on rodent models, lower vertebrates, and indeed, even invertebrate nervous systems. The 50th SfN reported on a "zoo” of Daphnias, inebriated fruit flies, severed zebrafish spinal cords, and RNAi-knocked roundworms having had specific populations of their limited subset of neurons knocked out by RNAi.


“I think, therefore I am?”

The purpose and function of the brain have kept philosophers busy for hundreds of years. We are now living in very exciting times where we finally are being able to make the tools and skills to embark on the global mapping of the detailed molecular identity and projections of every single neuron and glial cells in the human brain.

Overwhelmed by complex data sets we are now in a state of ordered confusion and at best a fragmented knowledge about how the brain wires and connects, the “connectome”. Still, we cannot define what consciousness is without referring to metaphysical metaphors. Some like Christof Koch at Allen Brain Atlas supports a reductionist view simply stating that consciousness can be confined to a limited circuit of neurons in the brain. It is a fascinating prospect that the neuroanatomists Golgi and Cajal at the turn of the 20th century, thought they had it all figured out by showing their ingenious silver impregnation methods able for the first time to discern sub-cellular details about the normal and pathological micro-anatomy of the brain.

The main conundrum of that day was whether the neurons were continuous or interconnected by what we today define as synaptic contacts. It is self-evident, however, that it is not enough knowing how single neurons work and fire together in isolation to understand the matter that builds up our minds.


The neuronal mosaic

Neurons, as it has turned out, exhibit striking and stochastic cellular diversity. How is this diversity generated? This is exceedingly difficult to study since neurons are diverse, subtypes intermingled, fail to divide, plus the fact that single-cell approaches have limited resolution.

The frequent occurrence in the human brain of “brain only” somatic mutations absent from blood DNA, may come as a surprise to most and may occur from the first cell division till the last. Single-cell genomes can differ by hundreds of mutations from one neuron to the next neighboring nerve cell causing what is called somatic “mosaicism”.

Autistic Spectrum Disorder, ASD show excess mutation frequency in critical exons of genes expressed in the early brain compared to normal siblings. De novo somatic mosaicism occurs in neuropsychiatric disorders, as can be exemplified by the somatic activation of the AKT3-mTOR pathway causing hemispheric developmental brain malformations.


Gene therapy of the brain

Application of gene therapies to correct peripheral disorders like cystic fibrosis or blood cancers is rather familiar, whereas tinkering with the genome of the CNS may sound a little like science fiction.

On the contrary, it now seems that the development of novel vectors and a growing understanding of how to administrate and disseminate these vectors in vivo has opened up entirely new possibilities to address genetic diseases of the brain otherwise unattainable by classical pharmacotherapy.

Gene therapies allow the removal of faulty or misexpressed proteins from the brain parenchyma by targeting mutated alleles. Lysosomal storage diseases are excellent target ailments exemplifying their use. In such diseases, progressive intracellular deposition of lysosomal substrates within lysosomes is the prime cause of cell death.


Microglia! the rising star(s)

One of the cell types that received a particularly hearty welcome at this year´s SfN summit was the microglia, the resident immune cells of the CNS, with a particular aptitude to adjust to microenvironmental changes.

These cells are multitasking, including tidying up debris, pruning of synapses, and regulation of injury response after demyelination of the brain. By analyzing thousands of individual isolated microglia using distinct sets of biomarkers, nine different microglial activation states have been identified in the mouse brain. The so-called reactive microglia are intimately involved in demyelinating disease of the brain including human multiple sclerosis (MS) lesions


Scientific dispute? Details matter!

Scientific candor and courage to share information are essential in the scientific world and nourishes scientific progress. A very good example of this was the “dual” (not duel!) concerned the controversy whether neurogenesis occurs in the adult hippocampus, or not.  Where Dr. Alvarez-Buylla failed to find any traces of young neurons, Dr. LLorens-Martin declares an opposite view, claiming that low-hippocampal neurogenesis actually continues, albeit at a low frequency, into the 9th decade of life in humans, persisting throughout physiological and pathological aging.

The discrepancy in their views is likely accounted for by methodological differences in the analyses of the brain tissues not least as regards tissue fixation and antigen retrieval.

This was just a minimal teaser on what really took place on the shore of Lake Michigan, the rest not accounted for here was just as interesting.