Connectome

within a human brain, as visualized by MRI tractography architecture of the human brain are visualized color-coded by traversing direction (xyz-directions mapping to RGB colors respectively). Visualization of fibers was done using TrackVis software. A connectome ( ) is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". These maps are available in varying levels of detail. A functional connectome shows connections between various brain regions, but not individual neurons. These are available for large animals, including mice and humans, are normally obtained by techniques such as MRI, and have a scale of millimeters. At the other extreme are neural connectomes, which show individual neurons and their interconnections. These are usually obtained by electron microscopy (EM) and have a scale of nanometers. They are only available for small creatures such as the worm C. elegans and the fruit fly Drosophila melanogaster, and small regions of mammal brains. Finally there are chemical connectomes, showing which neurons emit, and are sensitive to, a wide variety of neuromodulators. As of 2025, only C. elegans has such a connectome. The significance of the connectome stems from the realization that the structure and function of any brain are intricately linked, through multiple levels and modes of brain connectivity.…

within a human brain, as visualized by MRI tractography]] architecture of the human brain are visualized color-coded by traversing direction (xyz-directions mapping to RGB colors respectively). Visualization of fibers was done using TrackVis software. ]] A connectome ( ) is a comprehensive map of neural connections in the brain, and may be thought of as its "wiring diagram". These maps are available in varying levels of detail. A functional connectome shows connections between various brain regions, but not individual neurons. These are available for large animals, including mice and humans, are normally obtained by techniques such as MRI, and have a scale of millimeters. At the other extreme are neural connectomes, which show individual neurons and their interconnections. These are usually obtained by electron microscopy (EM) and have a scale of nanometers. They are only available for small creatures such as the worm C. elegans and the fruit fly Drosophila melanogaster, and small regions of mammal brains. Finally there are chemical connectomes, showing which neurons emit, and are sensitive to, a wide variety of neuromodulators. As of 2025, only C. elegans has such a connectome. The significance of the connectome stems from the realization that the structure and function of any brain are intricately linked, through multiple levels and modes of brain connectivity. There are strong natural constraints on which neurons or neural populations can interact, or how strong or direct their interactions are. Indeed, the foundation of human cognition lies in the pattern of dynamic interactions shaped by the connectome. Despite such complex and variable structure-function mappings, connectomes are an indispensable basis for the mechanistic interpretation of dynamic brain data, from single-cell recordings to functional neuroimaging. The terms connectome and connectomics were introduced independently by Olaf Sporns at Indiana University and Patric Hagmann at Lausanne University Hospital to refer to a map of the neural connections within the brain. This term was directly inspired by the ongoing effort to sequence the human genetic code—to build a genome. It was more recently popularized by Sebastian Seung's I am my Connectome speech given at the 2010 TED conference. In 2012, Seung published the book Connectome: How the Brain's Wiring Makes Us Who We Are.

Initial attempts at connectivity mapping

]] Throughout the 2000s, several investigators have attempted to map the large-scale structural architecture of the human cerebral cortex. One attempt exploited cross-correlations in cortical thickness or volume across individuals. Such gray-matter thickness correlations have been postulated as indicators for the presence of structural connections. A drawback of the approach is that it provides highly indirect information about cortical connection patterns and requires data from large numbers of individuals to derive a single connection data set across a subject group. Other investigators have attempted to build whole-brain connection matrices from DW-MRI imaging data. The Blue Brain Project attempted to reconstruct the entire mouse connectome using a diamond knife sharpened to an atomic edge, and electron microscopy for imaging tissue slices. They ended up in 2018 with an atlas providing information about major cell types, numbers, and positions in 737 regions of the brain.

Challenge for macroscale connectomics

The initial explorations in macroscale human connectomics were done using either equally sized regions or anatomical regions with unclear relationship to the underlying functional organization of the brain (e.g. gyral and sulcal-based regions). While much can be learned from these approaches, it is highly desirable to parcellate the brain into functionally distinct parcels: brain regions with distinct architectonics, connectivity, function, and/or topography. Accurate parcellation allows each node in the macroscale connectome to be more informative by associating it with a distinct connectivity pattern and functional profile. Parcellation of localized areas of cortex have been accomplished using diffusion tractography and functional connectivity to non-invasively measure connectivity patterns and define cortical areas based on distinct connectivity patterns. Such analyses may best be done on a whole brain scale and by integrating non-invasive modalities. Accurate whole brain parcellation may lead to more accurate macroscale connectomes for the normal brain, which can then be compared to disease states. Pathways through cerebral white matter can be charted by histological dissection and staining, by degeneration methods, and by axonal tracing. Axonal tracing methods form the primary basis for the systematic charting of long-distance pathways into extensive, species-specific anatomical connection matrices between gray matter regions. Landmark studies have included the areas and connections of the visual cortex of the macaque and the thalamocortical system in the feline brain. The development of neuroinformatics databases for anatomical connectivity allow for continual updating and refinement of such anatomical connection maps. The online macaque cortex connectivity tool CoCoMac and the temporal lobe connectome of the rat are prominent examples of such a database.

Alternatives to EM for detailed connectomes

Alternative techniques for mapping neural connectivity at the cellular level offer significant new hope for overcoming the limitations of classical techniques and for compiling cellular connectome data sets. Using Brainbow, a combinatorial color labeling method based on the stochastic expression of several fluorescent proteins, Jeff W. Lichtman and colleagues were able to mark individual neurons with one of over 100 distinct colors. The labeling of individual neurons with a distinguishable hue then allows the tracing and reconstruction of their cellular structure including long processes within a block of tissue. Another alternative approach to EM for to mapping connectivity was proposed in 2012 by Zador and colleagues. Zador's technique, called BOINC (barcoding of individual neuronal connections) uses high-throughput DNA sequencing to map neural circuits. Briefly, the approach consists of labelling each neuron with a unique DNA barcode, transferring barcodes between synaptically coupled neurons (for example using Suid herpesvirus 1, SuHV1), and fusion of barcodes to represent a synaptic pair. This approach has the potential to be cheap, fast, and extremely high-throughput. In 2022, a new technique called LICONN combined hydrogel expansion with light microscopy (as opposed to electron microscopy) to generate neuron level connectomes. The chief advantages are cheaper equipment (optical vs EM microscopes), faster data acquisition, and multi-color labelling.

Plasticity of the connectome

At the beginning of the connectome project, it was thought that the connections between neurons were unchangeable once established and that only individual synapses could be altered. However, evidence suggests that connectivity is also subject to change, termed neuroplasticity. There are two ways that the brain can rewire: formation and removal of synapses in an established connection or formation or removal of entire connections between neurons.

Small animals

Caenorhabditis elegans., commonly referred to as C. Elegans, is a small (<1&nbsp;mm) nematode (or roundworm). It has a very small nervous system with 302 neurons and about 5000 synaptic connections (as compared, say, to the human brain which has 100 billion neurons and more than 100 trillion synapses). It was the first animal with a fully reconstructed synaptic connectome, and is the only animal with a known chemical (neuropeptide) connectome. The C. elegans connectome reconstruction began with manual annotation of electron micrographs, published by White, Brenner et al., in 1986¹. Based on this seminal work, the first ever connectome (then called "neural circuitry database" by the authors) for C. elegans was published in book form with accompanying floppy disks by Achacoso and Yamamoto in 1992¹. The very first paper on the computer representation of its connectome was presented and published three years earlier in 1989¹ by Achacoso at the Symposium on Computer Application in Medical Care (SCAMC). The C. elegans connectome was later revised. The small size of the nervous system of C. elegans has allowed studies that would be difficult or impractical in larger organisms. These include changes during the animal's development., variability between individuals, both at the level of synapse and connection, despite an invariant cell lineage and changes during development and aging. Researchers found the biggest change with age is the wiring circuits, and that connectivity between and within brain regions increases with age. Other studies have combined the connectome with behavior, environmental influences, and other available information to study the connection between neuroanatomy and behavior, and suggested comparing the connectome to that of other animals, once available. Two other small animals with complete connectomes are the larvi of the ascidian Ciona intestinalis (177 CNS neurons, 6618 synapses including 1772 neuromuscular junctions and 1206 gap junctions) and Platynereis dumerilii (2728 neurons, 25,509 synapses). TED talk by Sebastian Seung: I am my connectome MITK Diffusion: Free software for the processing of diffusion-weighted MR data including connectomics

Text derived from https://en.wikipedia.org/w/index.php?oldid=1376454668 under CC BY-SA 4.0; modifications have been made.