Synapses degrade quickly
Posted: Sat May 23, 2026 2:31 pm
My core concern is how long synapses remain intact after death. Fundamentally, we don't really know the full answer to that, but I think we have some hints.
Here's the sequence of an electrical signal at a synapse:
-neuron
-long axon
-presynaptic bouton
-synapse
-postsynaptic spine
-dendritic tree
-recipient neuron
I've highlighted the two structures that we're mostly concerned with. The presynaptic bouton has a cytoskeleton that supports its shape. This cytoskeleton is composed mostly of microtubules and neurofilaments. They seem to degrade over hours instead of minutes, so I'm not really concerned about those. I'm instead concerned with the postsynaptic spine because its cytoskeleton is composed mostly of actin. Think of the actin as kind of like the loofah sponge in your shower, except that it's very dynamic. The structure is constantly rebuilding itself, and it requires active metabolism and ATP to do so. You have sugar powering this equilibrium for every moment of your entire life. As you are dying, blood flow and sugar stop being available for the first time ever. The dynamic structure of the postsynaptic spine cannot maintain itself and quickly gets distorted. The spine is extremely small, so it doesn't take much to lose enough structure to no longer be able to accurately trace the original connection path. How fast does this happen? Well, it seems to start within minutes and gradually degrades over an hour or two. Quality after a few minutes to tens of minutes is noticeably less. That doesn't mean complete loss, but it does mean that minutes do truly matter.
What do we do with this information? Well, it means we must move very quickly, obviously. It means we should prefer carotid artery access instead of a median sternotomy. It means there's no time for medications, an ice bath, or chest compressions. All of those things would be a distraction eating into precious time. It also means Medical Aid in Dying could significantly help quality.
We already know all these things, and we've talked about them for years, but it does help to remind ourselves of one of the main mechanisms responsible for quality loss. For example, much of the scientific literature glosses over this detail because it's not important for their goal. A brain bank can tolerate a delay of many hours without noticeable "damage" because they don't really need much of that fine synaptic detail.
Here's the sequence of an electrical signal at a synapse:
-neuron
-long axon
-presynaptic bouton
-synapse
-postsynaptic spine
-dendritic tree
-recipient neuron
I've highlighted the two structures that we're mostly concerned with. The presynaptic bouton has a cytoskeleton that supports its shape. This cytoskeleton is composed mostly of microtubules and neurofilaments. They seem to degrade over hours instead of minutes, so I'm not really concerned about those. I'm instead concerned with the postsynaptic spine because its cytoskeleton is composed mostly of actin. Think of the actin as kind of like the loofah sponge in your shower, except that it's very dynamic. The structure is constantly rebuilding itself, and it requires active metabolism and ATP to do so. You have sugar powering this equilibrium for every moment of your entire life. As you are dying, blood flow and sugar stop being available for the first time ever. The dynamic structure of the postsynaptic spine cannot maintain itself and quickly gets distorted. The spine is extremely small, so it doesn't take much to lose enough structure to no longer be able to accurately trace the original connection path. How fast does this happen? Well, it seems to start within minutes and gradually degrades over an hour or two. Quality after a few minutes to tens of minutes is noticeably less. That doesn't mean complete loss, but it does mean that minutes do truly matter.
What do we do with this information? Well, it means we must move very quickly, obviously. It means we should prefer carotid artery access instead of a median sternotomy. It means there's no time for medications, an ice bath, or chest compressions. All of those things would be a distraction eating into precious time. It also means Medical Aid in Dying could significantly help quality.
We already know all these things, and we've talked about them for years, but it does help to remind ourselves of one of the main mechanisms responsible for quality loss. For example, much of the scientific literature glosses over this detail because it's not important for their goal. A brain bank can tolerate a delay of many hours without noticeable "damage" because they don't really need much of that fine synaptic detail.