Absolutely, the brain is the most complicated system in the universe that we are aware of. Something I usually tell people when making comparisons between modern ANNs and biological brains is that there is more computational complexity in a single neuron than the largest ANN
All of this doesn't even go into the variation in proteins. For example, AMPA receptors are ion channels, right? One channel is made up of 4 subunits which each is a single polypeptide protein string folded up. There not only are multiple different subunits that can be swapped out to change the properties of the ion channel such as open time, conductance, and ion selectivity, but the subunits can also have posttranslational modifications such as phosphorylation that also changes these properties (besides selectivity iirc)
All of this allows incredible nuance for how this one channel responds to stimulation and add on top of that we get more or less AMPA receptors inserted in the membrane at a synapse. Now multiply all of that nuance times all of the synaptic boutons and other receptor proteins
Yet again adding more complexity are g-protein coupled receptors that aren't ion channels but cause other changes that may be longer lasting inside the neuron from impacting genetic expression or modifying epigenetics to impacting other ion channels or their expression and this is barely scratching the surface of overall complexity of one singe cell
We have billions of these fuckin things all interconnected in a complex web many having thousands of connections that are continuously being modified, created, and destroyed
And there are many more signaling pathways besides synaptic such as volume transmissions where neurotransmitters essentially diffuse away from the release site to hit receptors on the cell bodies of far away neurons, we have neuropeptides that can be released from the same synapse as other transmitters but only under specific conditions that can impact near or far cells, we have glia such as astrocytes and microglia that interact with synapses and help with cleanup, regulation, and of course more signaling
Lovely! And a single excitatory postsynaptic density is an amazingly complex aggregate of 500+ different protein species — perhaps hundreds of each type (see Seth Grant's work:
www.synaptome.genes2cognition.org
And yet we typically treat this amazing molecular complex as an “on-off” switch. What a joke of reductionism. A better crude metaphor is that a single synapse is a context-dependent microprocessor.
I think that's a good metaphor where context is the impact of previous states.
Every piece of the system is incredibly dynamic and has an huge degree of nuance which impacts the computation including within the synapse, the postsynaptic density, and the presynaptic neuron. The amount and content of vesicles as well as location and density of voltage gated calcium channels can change the content and quantity of signal sent. And that's before we talk about all of the other regulatory proteins presynaptically
All of this doesn't even go into the variation in proteins. For example, AMPA receptors are ion channels, right? One channel is made up of 4 subunits which each is a single polypeptide protein string folded up. There not only are multiple different subunits that can be swapped out to change the properties of the ion channel such as open time, conductance, and ion selectivity, but the subunits can also have posttranslational modifications such as phosphorylation that also changes these properties (besides selectivity iirc)
All of this allows incredible nuance for how this one channel responds to stimulation and add on top of that we get more or less AMPA receptors inserted in the membrane at a synapse. Now multiply all of that nuance times all of the synaptic boutons and other receptor proteins
Yet again adding more complexity are g-protein coupled receptors that aren't ion channels but cause other changes that may be longer lasting inside the neuron from impacting genetic expression or modifying epigenetics to impacting other ion channels or their expression and this is barely scratching the surface of overall complexity of one singe cell
We have billions of these fuckin things all interconnected in a complex web many having thousands of connections that are continuously being modified, created, and destroyed
And there are many more signaling pathways besides synaptic such as volume transmissions where neurotransmitters essentially diffuse away from the release site to hit receptors on the cell bodies of far away neurons, we have neuropeptides that can be released from the same synapse as other transmitters but only under specific conditions that can impact near or far cells, we have glia such as astrocytes and microglia that interact with synapses and help with cleanup, regulation, and of course more signaling