Bhau

Posted on Feb 03, 2022Read on Mirror.xyz

The Economy of Neurotransmitters

This post is part of a larger set of ideas about how Ethereum is a decentralized world-modelling computer, which you can find here. This post can be understood in isolation as well.

The brain is a distributed computing system, and it is also a network. Nodes in a network require coordination, and value exchange can emerge as an elegant solution. Crypto networks have taught us this: bottom-up self-organizing/spontaneously ordering systems will develop economies in order to survive, grow, and scale. More accurately these are crypto-economic networks, as they coordinate by transacting crypto-currencies/digital assets.

Crypto-economic networks - particularly Ethereum - resemble brain networks, and this becomes increasingly clear after neurotransmitters are viewed through an economic lens. Indeed, Neurotransmitters are the Money of the brain for they meet the three basic agreed upon requirements for something to be functioning as money:

ETH serves these functions

ETH Moneyness

The primary good transacted in the nervous system economy is electricity, and by extension, information. Hence, this can be understood as an Information Economy.

Action Potentials in the Information Economy

When neurons transmit electrical signals, the electricity is relayed in the form of Action Potentials. Action Potentials are thought to represent the smallest unit of information transmitted by neurons. An Action Potential develops when a series of positive charges accrues beyond a threshold (ranges from -40 mV to -55 mV) in the cell membrane (resting potential is around -70 mV), and trigger the charges to travel down the length of the axon. In this sense, neuronal signaling is all-or-none, 1 or 0; i.e. it is digital.

When Action Potentials are generated, colloquially, we say that the neuron is firing.

When the Action Potential reaches the axon terminal, chemicals known as Neurotransmitters (NTs) are released from the pre-synaptic neuron. NTs subsequently flow across the synaptic cleft and bind to dendritic receptors on the post-synaptic neuron.

A remarkable phenomenon unfolds.

The brain is conserving energy – minimizing free energy - at the biochemical level, by converting electrical energy into chemical energy and back into electrical energy. This occurs on the order of milliseconds throughout the entire nervous system, continuously.

When the NT binds to a post-synaptic neuron, the outcome is primarily binary. It conveys a message and signals the neuron to do one of two things:

  • Move closer towards triggering an action potential by making the membrane potential more net positive.
    • This is called De-polarization, and it is the result of positive ions flowing in and negative ions flowing out of the cell.
  • Move further away from triggering an action potential by making the membrane potential more net negative.
    • This is called Hyper-polarization, and it is the result of positive ions flowing out and negative ions flowing into the cell.

This is comparable to gas fees on Ethereum. EPSPs bring the neuron closer to firing action potentials = due to lower "base fees," transactions are more likely to be confirmed in the block. Vice versa for IPSPs.

An excitatory post-synaptic potential (EPSP) makes it more likely for a neuron to “fire,” therefore NTs that exert a depolarizing effect on neurons are said to be excitatory. The converse also applies; inhibitory NTs generate inhibitory post-synaptic potentials (IPSP) to hyper-polarize neurons.

There are many NTs in the human nervous system.

Dopamine and Serotonin are likely the most commonly known NTs, but Glutamate and GABA are by far more prevalent in the brain. Glutamate is the principal excitatory neurotransmitter, whereas GABA is the chief inhibitory messenger.

Unit of Account

Everything on the Ethereum network is accounted in terms of ETH. The most ubiquitous example is Gas, which is priced in Gwei (fraction of an Ether, seldom known as nanoeth), and is required for conducting transactions and smart-contract computations. As more decentralized applications have been built on Ethereum, Ether has become the de-facto way of accounting for a variety of things such as collateral, interest, options, perpetual swaps, and other financial primitives.

When NTs binds to a receptor, a variable and measurable change is induced in the neuron's membrane potential. In contrast to all-or-none Action Potentials, these are called Graded Potentials.

Only when enough depolarizing graded potentials are induced in the post-synaptic neuron, does the EPSP summation trigger an Action Potential:

Because Neurotransmitters alter the resting membrane potential…

…by either depolarizing or hyperpolarizing the membrane via Graded Potentials, they essentially Account for each Unit of ∆mV (change in milli-volts).

This unit of account varies with the kind of NT (Serotonin, Dopamine, etc.) as well as the specific type of receptor to which it binds (5-HT1, 5-HT3, D1, D4, etc.). At this time, the precise accounting of every NT + NT receptor combination remains to be uncovered.

Medium of Exchange

Because value must flow through Ether on the Ethereum Network, it is the de facto Medium of Exchange within a variety of decentralized applications.

As chemical messengers, NTs function like a bridging type of currency enabling neurons to exchange electricity. In this way, NTs serve as a Medium of Exchange.

Store of Value

The price of Ether relative to USD has increased by orders of magnitude since its inception in 2015. Ether is held by project teams in their treasuries, speculated upon, and is relatively scarce with a predictable supply growth and transparent monetary issuance policy; Ether is a Store of Value.

Similarly, NTs also function as a Store of Value. NTs are ephemeral because they are immediately removed from circulation after being released into the synaptic cleft. Reuptake by the pre-synaptic neuron is the main way in which this unfolds, where they are stored within vesicles for later use. In this sense, NTs are a Store of Value.

This reuptake process is inhibited by many psychotropic medications.

E.g. mechanism of action of the pharmaceutical treatment (Selective Serotonin Reuptake Inhibitors; SSRI) for Major Depression blocks this process:

Neurotransmitter Moneyness

Neurotransmitter Synthesis

Avoiding single points of failure through Decentralization

The most ubiquitous Neurotransmitters – Glutamate and GABA – are produced locally inside neurons throughout the brain. Because these are the primary excitatory and inhibitory NTs, respectively, this global production appears to be an effective design property from a systems level perspective. In comparison, other NTs for the most part, are synthesized within specialized factories (nuclei) before they are transported to other neurons:

  • Dopamine: Substantia Nigra and Ventral Tegmental Area
  • Serotonin: Raphe Nuclei
  • Norepinephrine: Locus Coeruleus
  • Acetylcholine: Nucleus Basalis of Meynert in the Basal Forebrain

The benefits of decentralizing production are underscored by the presence of ailments like Parkinson’s disease, which results from the degeneration of dopamine secreting neurons in the Substantia Nigra Pars.

Everything in the brain is heavily inter-connected, therefore systems often overlap and things are not clear cut. E.g. the Locus Coeruleus is also affected in Parkinson’s disease.

Neurotransmitter Composability

ETH and other ERC-20 tokens/protocols (AAVE, SNX, MKR, etc.) are regarded as money Lego blocks in the Decentralized Finance ecosystem, because they resemble bricks that can be freely combined with others to build more sophisticated products and services. E.g. supplying assets to Aave outputs "aTokens" (Aave-tokens) which represent the balance + interest earned on the underlying asset. These interest-yielding tokens can be subsequently supplied to other dApps, such as aLINK in the yEarn ecosystem.

There are many more (Composability in Ethereum):

Likewise, Neurotransmitters are also composable:

Each molecule in the synthesis pathway from Phenylalanine to Epinephrine serves specific and generalizable functions throughout the human body and nervous system. I.e. Phenylalanine is an amino acid, Dopamine and Norepinephrine are neurotransmitters, and Epinephrine is a hormone also known as Adrenaline.

This fosters robustness and anti-fragility, in comparison to fragility characterizing the traditional finance system.

Robust and Anti-fragile

Fragile

Neurotransmitter Functions

Neurotransmitters are ultimately tokens for transmitting information/signals through the brain, and their money-like characteristics optimize this function.

Different strokes for different "forks"

Every neuronal nucleus has numerous projections to various brain regions. E.g., the Ventral Tegmental Area (VTA) outputs efferent fiber projections through the Mesocortical pathway to the Prefrontal Cortex, and the Mesolimbic pathway to the Nucleus Accumbens.

Two important dopaminergic pathways are depicted above.

As these pathways “fork” and separate anatomically from the point of origin, so does the function of Dopamine along the corresponding projections, i.e. DA function in the mesolimbic pathway regulates incentive salience, reinforcement learning, novelty seeking, and reward processing. Reward processing has been extensively studied in the context of addiction because dopaminergic projections from the VTA synapse with D-1 type medium spiny neurons inside the Nucleus Accumbens (NAcc) – colloquially known as the pleasure center of the brain.

This region is compromised in digital media overuse, and in turn can manifest phenomenologically as mental health disturbances. E.g. when we see that our social media posts or images are “liked,” this information is translated into DA release within our NAcc. Over time the brain becomes dependent on the information triggering bursts of DA, similar to a lab rat helplessly pushing levers of cocaine.

This raises important questions:

  1. Could DLT projects like Basic Attention Token develop use cases to mitigate dopaminergic hijacking of the brain?
  2. What insights can we apply from the interplay between various neurotransmitter systems as we build out a multi-chain world?

In comparison to the Mesolimbic pathway, DA function in the Mesocortical pathway regulates cognitive control and emotional responses. The Prefrontal Cortex, occasionally referred to as the “seat of judgment,” is the primary area involved in executive functioning and complex attentional processes. A shortage of dopamine in this region is involved in the pathophysiology of cognitive disorders like ADHD, though research is uncovering a deeper pathophysiology. Myriad research studies have unequivocally demonstrated that the Prefrontal Cortex and its associated networks function aberrantly in patients with psychiatric illness.

Take home point:

Neuronal projections have different receptors, and this enables differential functioning of NTs along corresponding pathways.

Next: A Distributed Ledger