Brain Plastination

Neuroscientists today can preserve small volumes (<1mm³) of animal brain tissue immediately after death with incredible precision – the features and structure of every synapse within these volumes is well-protected down to the nanometer scale, using an inexpensive, room-temperature process of chemical fixation and plastic embedding, or "plastination." The image to the right is an example of plastination and local circuit tracing, occurring in leading neuroscience labs around the world today.

This work immediately raises the question:

Brain Plastination “Can the standard chemical fixation and plastic embedding technique used for electron microscopic investigation of brain circuitry be adapted to preserve the synaptic connectivity of an entire human brain?”

This is a well-defined scientific question, and we now have the tools necessary to answer this question definitively. This question is of great importance, for at least two reasons:

  1. The new science of connectomics is gearing up to map the connectome, the full synaptic connectivity of an entire brain. The first major milestone for mammals will be a mouse brain and eventually, we will map an entire human brain. Development of whole brain chemical fixation and plastic embedding procedures seems an absolute prerequisite for such a scientific endeavor.
  2. Since most neuroscientists today would agree that our unique memories are written into the brain at the level of the cell body and its synaptic connections, successful nuclear and synaptic preservation of an entire brain after clinical death would very likely preserve the memories and identities of all individuals who might wish to do so, for themselves, for their loved ones, for science, or society. There are many who would desire the option to perfectly and inexpensively preserve their brains at the nanometer scale today, for the possibility that future science might be able to read their memories or restore their full identities, as desired.

With respect to the latter, millions of people have at least briefly considered the possibility of having themselves or their loved ones cryonically preserved (very low-temperature preservation and storage) in the hope that future medical technology might revive and cure them. Yet so far, only a few thousand have entered contracts to do so. Why? There are many potential reasons, yet one is a particularly tractable challenge to the scientific community. At present there is scarce evidence that the existing practice of cryonics preserves the precise wiring of our brain’s hundred billion neurons. Cryonics techniques have improved substantially in recent years, but the fundamental question remains:

“Does cryonics as practiced today adequately preserve the synaptic connectivity of an entire human brain?”

This is also a well-defined scientific question that can be answered today. This question is of great importance, particularly to terminally ill patients wishing to preserve their memories or identities today, for which cryonic preservation of unknown efficacy is presently their only alternative.

We at the Brain Preservation Foundation are dedicated to seeing that these questions are answered in a definitive scientific manner as soon as possible and to uncover the truth about the quality of today’s preservation techniques and to spur research into better techniques.


* In the types of electron microscopy neuroscientists commonly use (FIBSEM, etc.), preserved neural tissue can be visualized down to about a 6 nanometer resolution. This allows them to directly see each neuron's synapses and dendrites (connections to other neurons). This level of detail also includes the ability to image, directly and indirectly (via molecular probes), many elements of the "synaptome," the number and types of special proteins (vesicles, signaling proteins, cytoskeleton), receptors (Glutamate, etc.), and neurotransmitters (at least six types in human neurons) that are known to be involved in long-term learning and memory at each synapse in the brain, and elements of the "epigenome" (learning-based DNA methylation and histone modifications) in the nucleus of each neuron. It remains an open question in neuroscience exactly which features of the synaptome and epigenome need to be preserved to retain memory and identity in each species. We know simpler connectomes, synaptomes, and epigenomes are used in organisms with simpler memories (C. elegans, Drosophila, Aplysia, etc.), and that the vast majority of neural molecules are not involved in learning and memory, but support other cell functions necessary for life.

* Chemical Fixation and Cryonics both preserve the fats, proteins, sugars, and DNA in living neurons, and fix them effectively in place, and relevant membrane receptors stay in their normal distributions as well, as verified by antibody probes. What we don't know yet is if this happens reliably everywhere during whole brain chemical and cryonic preservation. We also don't know the full complement of small molecules and cytoskeletal features in our neurons and glia that are necessary to memory and identity, and which molecular signal states (eg., phosphorylation, methylation) are important. But our knowledge of the molecular basis of learning and memory continues to rapidly grow, aided by exciting new neuroscience techniques (optogenetics, viral tagging, protein microarrays, etc.). Our ability to scan and verify is also rapidly improving. New types of electron microscopy, such as Cryo-TEM, can image at an amazing 3 angstrom resolution, 50 times greater magnification than FIBSEM, a scale where brain proteins and even individual atoms can be directly seen.

Current Brain Preservation Technology is focused on the connectome, imaged at FIBSEM resolution. As neuroscience advances, we may learn that certain features of the synaptome and epigenome not presently observable by FIBSEM must also be preserved. Additional technology may make use of other verification methods and even higher resolution imaging if necessary. As neuroscience continues to advance, reliable and affordable protocols may be found to better preserve those brain structures that give rise to our memories and identities, according to our best evidence to date.