Very recommendable! Amazing stuff! Comprehensive review and critique of connectome research. Learn that often dispassionate scientists can be voyeurs too. :-)
In some sense connectomics is a rather primitive approach to understand the functioning of the brain. E.g. it does not tell us much about the chemical communication between neurons etc.
"Last summer a group of Harvard University neuroscientists and Google engineers released the first wiring diagram of a piece of the human brain. The tissue, about the size of a pinhead, had been preserved, stained with heavy metals, cut into 5,000 slices and imaged under an electron microscope. This cubic millimeter of tissue accounts for only one-millionth of the entire human brain. Yet the vast trove of data depicting it comprises 1.4 petabytes [data]’ worth of brightly colored microscopy images of nerve cells, blood vessels and more. ...
including new types of cells never seen in other animals, such as neurons with axons that curl up and spiral atop each other and neurons with two axons instead of one. These findings just scratched the surface ...
In fact, the only species for which there is yet a comprehensive connectome is Caenorhabditis elegans, the humble roundworm.
Nevertheless, the masses of connectome data that scientists have amassed from worms, flies, mice and humans are already having a potent effect on neuroscience. ...
Recent work with C. elegans has demonstrated the power of large-scale connectomics. One experiment showed that it’s sometimes possible for scientists to predict the behavior of an animal from a knowledge of its connectome; another hinted at rules governing the linkage of neurons into working circuits. Those successes, however, also underscore how far large-scale connectomics still needs to go before it can tackle much more complex creatures. ...
About 35 years ago, the first full-brain wiring diagram was completed for the roundworm. For its time, the effort was heroic, even though the animal has only 302 neurons in its brain. It was carried out through the painstaking process of hand-drawing neuronal connections on printouts of electron microscopy images. It took more than 15 years to complete. ...
This approach is leading to impressive progress in understanding these animals. In a report in Cell published in September, scientists used the worm connectome to describe one of the most complex behaviors in the natural world: sex. Using video and calcium imaging — which measures and traces activity in brain cells — they recorded C. elegans during the act of mating. Videos showed the worms slithering around one another in serpentine patterns while white light from fluorescent proteins indicating neuronal activity flickered on and off along the length of their slender bodies. ...
For example, it has been known for some time that in C. elegans, the connections between neurons dramatically reorganize themselves between birth and adulthood. To understand how the brain changes throughout development, in a recent paper in Nature ... compared the connectomes of eight genetically identical roundworms ranging between larval and adult stages.
The most interesting finding of the study ... was that even though the worms were genetically identical, as much as 40% of the connections between nerve cells in their brains differed. Moreover, the connections that varied between individuals were weaker than those that were similar. Stronger connections that contained 100 synapses or more were consistent across multiple organisms.
... this finding points to the power of brain-map comparisons in bulk ... because each connectome is slightly different,” ... finding points to the existence of two classes of connections: variable ones and consistent ones. ...
When ... mapped the snippet of human brain, for example, they had no idea whether the strange things they saw were normal or one-offs due to the unique history and genetic makeup of the person. If they could map equivalent samples from 100 human brains, then they would get some clarity on these unknowns, but at 1.4 petabytes per brain, that is unlikely to happen anytime soon. ...
Nevertheless, connectomics is making important progress even where it can’t yet be large scale and where only partial connectomes exist. Work in the fruit fly, Drosophila melanogaster, is particularly far along, both in the larva (which has about 10,000 neurons) and in the adult (with about 135,000 neurons). Last year, researchers ... released a synapse-level “hemi-brain” connectome that mapped many important control centers in the fly’s brain. This led to an important announcement in October, when neuroscientists uncovered dozens of new neuron types and circuits that seem to aid in fly navigation. ...
What Connections Can’t Do
The successes of connectomics can be bittersweet. For many years, a central criticism of connectomics has been that it is insufficient to explain how the brain functions. ...
Another limitation of the connectome is that it doesn’t tell us anything about the quality of the connections: whether they are strong or weak. It simply tells us that there is a connection. ... neurons make thousands of connections with other neurons in vast networks full of redundancies and pathways with overlapping functions. ... Connectomics also tells us almost nothing about the brain chemicals called neuromodulators, which circulate through the fluid surrounding neurons, unlike the neurotransmitter chemicals released precisely within the synaptic connections between neurons. They represent another way that cells in the brain communicate with one another. ..."
From the abstract:
"We acquired a rapidly preserved human surgical sample from the temporal lobe of the cerebral cortex. We stained a 1 mm3 volume with heavy metals, embedded it in resin, cut more than 5000 slices at ∼30 nm and imaged these sections using a high-speed multibeam scanning electron microscope. We used computational methods to render the three-dimensional structure containing 57,216 cells, hundreds of millions of neurites and 133.7 million synaptic connections. The 1.4 petabyte electron microscopy volume, the segmented cells, cell parts, blood vessels, myelin, inhibitory and excitatory synapses, and 104 manually proofread cells are available to peruse online. Many interesting and unusual features were evident in this dataset. Glia outnumbered neurons 2:1 and oligodendrocytes were the most common cell type in the volume. Excitatory spiny neurons comprised 69% of the neuronal population, and excitatory synapses also were in the majority (76%). The synaptic drive onto spiny neurons was biased more strongly toward excitation (70%) than was the case for inhibitory interneurons (48%). Despite incompleteness of the automated segmentation caused by split and merge errors, we could automatically generate (and then validate) connections between most of the excitatory and inhibitory neuron types both within and between layers. In studying these neurons we found that deep layer excitatory cell types can be classified into new subsets, based on structural and connectivity differences, and that chandelier interneurons not only innervate excitatory neuron initial segments as previously described, but also each other’s initial segments. Furthermore, among the thousands of weak connections established on each neuron, there exist rarer highly powerful axonal inputs that establish multi-synaptic contacts (up to ∼20 synapses) with target neurons. Our analysis indicates that these strong inputs are specific, and allow small numbers of axons to have an outsized role in the activity of some of their postsynaptic partners."
New Brain Maps Can Predict Behaviors | Quanta Magazine Rapid advances in large-scale connectomics are beginning to spotlight the importance of individual variations in the neural circuitry. They also highlight the limitations of “wiring diagrams” alone.
