Update 2026-06-06-tripartite_synapse_v2.md
This commit is contained in:
@@ -2,7 +2,160 @@
|
|||||||
include_toc: true
|
include_toc: true
|
||||||
---
|
---
|
||||||
|
|
||||||
# Tripartite Synapse — Scope & Context Aware Pseudocode v2
|
# Neuron, budget, traces and behaviours
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## Conventions: The Language of the System
|
||||||
|
|
||||||
|
The system operates across two scopes and multiple contexts. The **DAY scope** is the organism's active period — all fast and intermediate behaviors run here, structural variables are read but never permanently written, and every action leaves a trace that may or may not survive to the NIGHT. The **NIGHT scope** is when structural commits execute, budgets replenish, and all DAY traces are either converted into permanent architecture or cleared. Within each scope, each compartment operates in a specific **context** — AP or NOT_AP for the presynapse, bAP or NOT_bAP for the postsynapse, and CONTINUOUS for the astrocyte and dendritic branch — that determines which behaviors are permitted to run.
|
||||||
|
|
||||||
|
Every variable in the system is either a **state variable**, a **trace**, or a **budget**. State variables describe the current condition of a compartment. Traces are modifications deposited by a behavior that persist beyond the moment and bias future behaviors — they are the system's memory between contexts. Budgets are shared resource pools that constrain how much of any behavior can actually execute, and they ensure that nothing in the system is free.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## Shared Resource Pools: The Economy Before Any Behavior Runs
|
||||||
|
|
||||||
|
Before any spike fires or any receptor moves, the system's capacity for change is already determined by the state of its shared resource pools. These pools exist at four nested territorial levels, and they are the reason that what happens at one synapse has consequences for all its neighbors.
|
||||||
|
|
||||||
|
The axonal arbor maintains a shared pool of vesicle scaffold proteins — RIM, Munc13, and VGCC subunits — that every bouton on that axon must draw from when it wants to expand its active zone. It also maintains a mitochondrial ATP capacity that sets the ceiling on how many release events can occur before the energy supply is exhausted and boutons begin going silent. A set of tagged boutons tracks which sites are currently in competition for proteins drifting along the axon.
|
||||||
|
|
||||||
|
The dendritic branch maintains its own receptor reserve — a local endosomal pool of AMPA receptors held near the spines that can be rapidly inserted without waiting for the soma — alongside actin machinery for spine enlargement, a protein flux arriving from the soma, a local pool of stored mRNAs that branch ribosomes can translate immediately, and its own mitochondrial ATP budget. The set of tagged spines on the branch tracks which sites are competing for these local resources.
|
||||||
|
|
||||||
|
The astrocyte territory — which in humans wraps hundreds of thousands of synapses — maintains pools of serine racemase enzyme for D-serine synthesis, glutamate transporter proteins for clearance, extracellular matrix proteins for structural sealing, and a finite number of perisynaptic process extensions that it can selectively allocate to different synapses. All of these draw from a single ATP budget that is itself ultimately capped by the glucose supply from the nearest blood capillary — a hard vascular ceiling that cannot be exceeded regardless of demand.
|
||||||
|
|
||||||
|
The soma maintains its own pools of synthesis capacity, receptor production rate, organelles for shipping to branches, and mRNA transcription rate. These are the upstream sources that replenish the branch-level pools, and their rate is set by the CREB transcription state left over from DAY activity — meaning the soma's production capacity during NIGHT is determined by how the DAY went.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## Budget Allocation: Constraint Before Commitment
|
||||||
|
|
||||||
|
When any compartment wants to draw structural resources, it does not simply take them. It calls a budget allocation function that checks what is available, applies a priority weighting based on whether that site has planted a synaptic tag, grants only what can be afforded, and decrements the pool accordingly. If the grant is smaller than the request — because the pool is partially depleted by competing synapses — the deficit is queued for the next NIGHT cycle and heterosynaptic depression is triggered in untagged neighbors. The neighbors lose resources not because any signal told them to weaken, but because the pool was exhausted before reaching them.
|
||||||
|
|
||||||
|
The astrocyte allocation has an additional layer: all three of its resource draws — D-serine, ECM proteins, and process extensions — are individually capped by their specific pools, and then the combined ATP cost of all three is checked against the total ATP budget. If the ATP cost would exceed the budget, all three grants are scaled down proportionally. This means a heavily loaded astrocyte serving many simultaneously active synapses delivers partial support to each rather than full support to a few.
|
||||||
|
|
||||||
|
Budget replenishment runs continuously but peaks during the NIGHT scope. The soma's protein synthesis rate, driven by CREB activation accumulated during DAY, determines how fast the dendritic branch pools refill. The astrocyte's pools recover at rates set by enzyme synthesis and ECM production machinery, with process extensions recovering the slowest — on a timescale of hours — which is why a fully deployed astrocyte cannot immediately reallocate its walls to a new synapse. The vascular glucose ceiling is the one parameter in the entire system that cannot be increased by any molecular mechanism — it is set by blood flow and capillary density, and it sets the absolute limit on how much simultaneous structural change the system can support.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## DAY Scope — Presynaptic Bouton
|
||||||
|
|
||||||
|
### Context: AP
|
||||||
|
|
||||||
|
When an action potential arrives, the first check is not biological but economic: does this bouton's local mitochondrial capacity have enough ATP to afford the release? If not, the bouton goes silent regardless of the electrical input. This is the energy gate that prevents a depleted axon from continuing to operate at full output — it is not a regulatory decision but a resource constraint.
|
||||||
|
|
||||||
|
If the budget permits, calcium floods in through voltage-gated channels. The key quantity is not the peak calcium but the residual: the calcium left over from previous spikes that has not yet decayed. This residual is the presynaptic memory of recent activity — a trace that accumulates with repeated firing and fades with silence on a timescale of roughly 100 milliseconds. The current release probability is biased by this residual, meaning a bouton that has been firing recently is primed to release more than one that has been silent. Vesicles are released probabilistically from the readily-releasable pool, glutamate fills the cleft, and the pool shrinks by exactly the number released. The mitochondrial budget decrements.
|
||||||
|
|
||||||
|
If enough glutamate escapes the cleft to reach the low-affinity mGluR2/3 receptors on the presynaptic membrane, an autoinhibitory brake engages. The Gi-coupled cascade suppresses adenylyl cyclase, reducing cAMP and directly dampening voltage-gated calcium channel opening. This is a negative feedback loop entirely within the presynaptic compartment: excess output detected, output probability reduced, without any postsynaptic input. The RRP is then partially refilled by the astrocyte's lactate supply, but only to the extent that lactate is available — another resource gate.
|
||||||
|
|
||||||
|
### Context: NOT_AP
|
||||||
|
|
||||||
|
Between spikes, the presynapse is not idle. The residual calcium trace continues to decay passively — if spikes do not keep arriving, the facilitation advantage erodes. If recent firing history has been consistently above 20 Hz, the reserve pool is mobilized toward the readily-releasable pool, making more vesicles available for the next burst — but only if the reserve is non-empty, meaning this mobilization is itself budgeted by whatever was stored during prior quiescence. If firing history has been sparse, release probability drifts downward.
|
||||||
|
|
||||||
|
The more important event in the NOT_AP context is the neuromodulatory broadcast. When dopamine or norepinephrine arrives above threshold, PKA activity rises and a synaptic tag is planted — the bouton is added to the set of axon-tagged boutons competing for drifting structural proteins. This tag is a trace of the neuromodulatory context that will persist into the NIGHT scope: if a structural commit runs before the tag expires, this bouton gets priority access to the axonal protein pool.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## DAY Scope — Dendritic Spine
|
||||||
|
|
||||||
|
### Context: NOT_bAP
|
||||||
|
|
||||||
|
The NOT_bAP context is where the Hebbian anticipation window opens. Glutamate arriving from the presynapse activates AMPA receptors, depolarizing the spine membrane. If this depolarization is sufficient — and crucially if D-serine supplied by the astrocyte is present as a co-agonist — the NMDA receptor's magnesium block is ejected and calcium begins to enter. The amplitude and speed of this calcium rise are recorded as traces: amplitude encodes whether the event was strong enough for LTP, speed distinguishes LTP-driving fast rises from LTD-driving slow ones.
|
||||||
|
|
||||||
|
The synaptic tag is planted here, in this context, before the back-propagating AP arrives to confirm coincidence. The trigger for tag planting is the calcium rise combined with NMDA opening — the system is tagging the moment it detects an incoming signal strong enough to potentially be worth encoding, before it knows whether the postsynaptic cell actually fired. This is the Hebbian anticipation: the forward glutamate signal is the candidate event, and the tag is the molecular record of that candidacy. The spine is simultaneously added to the dendritic branch's pool of tagged spines, entering competition for local protein resources. If the neuromodulator context gate has already been set by PKA, the AMPA insertion threshold is lowered, making the eventual structural commit easier.
|
||||||
|
|
||||||
|
### Context: bAP
|
||||||
|
|
||||||
|
When the back-propagating action potential arrives from the soma down the dendritic tree, it depolarizes the spine further. This is the confirmation signal. If a tag was planted just before the bAP — meaning the forward glutamate signal and the retrograde AP signal coincide in time — the calcium rise is amplified beyond the LTP threshold, confirming genuine Hebbian coincidence. The bAP did not cause the calcium rise; it amplified one that was already in progress, retroactively validating the tag that was planted in anticipation.
|
||||||
|
|
||||||
|
If no tag was present — if the bAP arrives at a spine that received no glutamate signal — the membrane depolarizes transiently but no calcium amplification occurs and no trace is deposited. The spine passes through the bAP context without consequence. This asymmetry is the core of spike-timing-dependent plasticity: the order matters, and the tag mechanism enforces the order by requiring the forward signal to precede the backward one by enough time to plant the tag before the bAP confirms it. At the end of the bAP context, the sodium-potassium pump resets the membrane, drawing on the astrocyte's lactate supply, and the soma ATP budget decrements to pay for the propagation cost of the bAP itself.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## DAY Scope — Dendritic Branch
|
||||||
|
|
||||||
|
### Context: CONTINUOUS
|
||||||
|
|
||||||
|
The dendritic branch runs continuously as an integrator and distributor, operating in both directions simultaneously. Upward, it integrates the membrane potentials of all spines on its length into a branch voltage that propagates toward the soma and contributes to whether a somatic action potential fires. It also propagates the back-propagating AP downward from the soma toward the spines, but its geometry matters: bAP amplitude decays with distance from the soma, meaning spines at the distal end of a long branch receive a weaker confirmation signal than proximal spines. This geometry is itself a slow structural trace — branches that have grown longer or lost mitochondrial density will propagate bAPs less faithfully.
|
||||||
|
|
||||||
|
The branch accumulates its own calcium signal driven by the bAP and by spillover from active spines, but this calcium decays more slowly than spine calcium — it integrates across multiple spines and persists for hundreds of milliseconds. When enough spines on the same branch are co-active, a branch-level tag is planted. This is the branch's version of the synaptic tag: a marker that this branch as a whole has been meaningfully recruited, which triggers local BDNF release — a trace that signals branch-level survival and growth pressure to the soma.
|
||||||
|
|
||||||
|
When a branch tag is set and the local mRNA pool is non-empty, the branch ribosomes begin translating stored mRNAs into structural proteins locally, without waiting for the soma. This local translation provides a fast protein supply that can support early structural changes within minutes rather than hours. The translation itself draws from the branch mitochondrial budget, so a branch that is energetically depleted cannot translate even if its mRNA pool is full. The acetylcholine broadcast modulates the global LTP threshold continuously in this context — during periods of high attentional drive, the threshold lowers across all branches simultaneously.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## DAY Scope — Soma
|
||||||
|
|
||||||
|
### Context: AP
|
||||||
|
|
||||||
|
The soma fires an action potential when integrated dendritic input crosses the firing threshold — itself a variable that is modulated by the neuromodulatory state. When it fires, calcium enters the nucleus — a trace that accumulates with firing rate and decays over seconds. This nuclear calcium is the signal that gates CREB phosphorylation in the soma, and CREB phosphorylation is the trace that determines how much protein synthesis runs during the subsequent NIGHT scope. But CREB phosphorylation requires both nuclear calcium above threshold AND PKA activity above threshold — it is a coincidence gate at the somatic level, just as NMDA opening is a coincidence gate at the spine level. Both the activity pattern (nuclear calcium) and the neuromodulatory context (PKA) must align for the gene expression program to activate. When they do, Arc mRNA and BDNF production begin — both traces that will be shipped to active dendritic branches during the NOT_AP context.
|
||||||
|
|
||||||
|
### Context: NOT_AP
|
||||||
|
|
||||||
|
Between somatic spikes, the soma integrates dendritic inputs and manages the distribution of resources to branches. It ships Arc mRNA preferentially to tagged branches, whose tags were planted during the DAY based on spine-level calcium events. It queues organelle deliveries to branches ranked by their branch calcium levels — the most active branches receive mitochondria first. This shipping process is itself budgeted: the organelle pool is finite, and a soma that has been heavily depleting its pool during a period of high activity will have fewer organelles to ship until NIGHT replenishment runs.
|
||||||
|
|
||||||
|
The neuromodulatory broadcast in the NOT_AP context sets the PKA gate simultaneously across all compartments: GluA1-Ser845 priming lowers the AMPA insertion threshold at all tagged spines, DARPP-32 phosphorylation silences the LTD phosphatase globally, and CREB activation opens the gene expression gate. None of these actions write any structural variable — they are traces that bias what the NIGHT scope will commit.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## DAY Scope — Astrocyte
|
||||||
|
|
||||||
|
### Context: CONTINUOUS
|
||||||
|
|
||||||
|
The astrocyte operates without discrete contexts — it monitors its entire territory continuously. Glutamate clearance runs at all times at a rate set by the density of transporter proteins currently deployed, drawing from the ATP budget with every cycle. When spillover crosses the low-affinity mGluR5 threshold — signaling that the cleft is genuinely saturated rather than merely active — the astrocyte's internal calcium rises proportionally to the spillover level. This local calcium rise drives D-serine secretion, but the amount secreted is capped by the current serine racemase enzyme capacity, which may be partially depleted if many neighboring synapses are simultaneously demanding co-agonist support. A busy astrocyte territory delivers partial D-serine to many synapses rather than full D-serine to a few — the support is rationed automatically by the enzyme pool.
|
||||||
|
|
||||||
|
The same spillover simultaneously activates the presynaptic mGluR2/3 brake through a completely different receptor arm, reducing vesicle release probability at the source of the overflow. This push-pull is not coordinated by any signal — it is a structural consequence of the two receptor types sitting on different cells with different G-protein couplings, activated by the same diffusing ligand at the same moment.
|
||||||
|
|
||||||
|
The astrocyte checks continuously whether its local calcium has exceeded the global overload threshold. If it has, a soma-wide calcium wave fires and the shockwave lockdown executes — a circuit-breaker that mass-internalizes postsynaptic AMPA receptors, hyperpolarizes the membrane, and clusters presynaptic calcium channels for maximum signal preservation, all while rapidly depleting the astrocyte's ATP budget. The lactate pipeline runs in parallel at all times, converting glucose to lactate up to the vascular ceiling and distributing it in fractions to the presynapse, postsynapse, and dendritic branch — the fractionation determining which compartment gets refueled first under high demand.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## Special Case: Shockwave Lockdown
|
||||||
|
|
||||||
|
The shockwave lockdown can trigger in either scope. It bypasses all budget gates — it is an emergency override that executes regardless of resource availability — but it pays a large ATP cost that leaves the astrocyte depleted and slower to support normal plasticity events for some time afterward. AMPA receptors are mass-internalized and returned to the dendritic reserve pool rather than destroyed, meaning they are recoverable when the emergency passes.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## NIGHT Scope — All Compartments
|
||||||
|
|
||||||
|
The NIGHT scope opens with budget replenishment. Soma protein synthesis rate, which peaked because CREB was activated during DAY, now drives the highest protein production of the cycle. Branch-level pools refill from this production — receptor reserves, actin machinery, mRNA pools, and mitochondrial capacity all recover at rates proportional to how much CREB-driven expression ran. The astrocyte's pools replenish on their own schedules, with process extensions recovering the most slowly.
|
||||||
|
|
||||||
|
The soma then processes its shipping queue: organelles deferred during DAY are delivered to the branches that ranked highest by calcium activity. Once the queues are resolved, the structural commit function runs for every synapse that carries a tag.
|
||||||
|
|
||||||
|
### PRE — Structural Commit
|
||||||
|
|
||||||
|
The presynapse draws from the axonal protein pool to expand its active zone. What it receives is proportional to how much remains in the pool after competing tagged boutons have drawn their shares. The expansion commits permanently: the active zone grows, more docking slots are installed, calcium channels cluster more tightly beneath the zone, and baseline release probability rises. These are slow traces that will read by every AP context in every subsequent DAY scope. If the pool was insufficient for the full requested expansion, the deficit is queued for the next NIGHT and the partial expansion is committed immediately. In the LTD branch, the process runs in reverse and the proteins dismantled from the active zone are returned to the shared pool, where they become available to other boutons.
|
||||||
|
|
||||||
|
### POST — Structural Commit
|
||||||
|
|
||||||
|
The postsynapse draws from the branch receptor reserve and actin machinery. CaMKII, activated by the calcium trace deposited during DAY, anchors new AMPA receptors into the membrane surface — the number anchored determined by how many receptors the budget granted. The spine head physically enlarges in proportion to the actin machinery available. Both changes are slow traces that will be read by every NOT_bAP context in every subsequent DAY. Deficits are queued. In the LTD branch, phosphatase PP1 drives receptor internalization, and the internalized receptors are returned to the branch reserve pool — again conserving the total receptor count across the segment rather than destroying it.
|
||||||
|
|
||||||
|
### DEND — Structural Commit
|
||||||
|
|
||||||
|
The dendritic branch receives the organelles shipped from the soma, permanently increasing its local mitochondrial density — a slow trace that will improve bAP propagation fidelity and local translation capacity in future DAY scopes. Arc mRNA stored in the branch pool is translated into structural proteins that expand the local protein flux, making the branch more self-sufficient for future plasticity demands. If BDNF-TrkB signaling crossed its survival threshold during DAY — meaning the branch was genuinely and collectively active — mitochondrial density is further reinforced, stabilizing the branch architecture. If it did not cross the threshold, mitochondrial density declines slightly, making the branch progressively less capable of supporting future plasticity. This is the branch-level version of the use-it-or-lose-it logic: not a binary decision but a continuous drift in one direction or the other depending on whether BDNF traces accumulated during DAY.
|
||||||
|
|
||||||
|
### SOMA — Structural Commit
|
||||||
|
|
||||||
|
The soma's NIGHT work is primarily generative rather than structural in the local sense. CREB-driven transcription produces new proteins, receptors, and mRNAs at the highest rate of the cycle, replenishing all downstream pools. Organelle biogenesis runs — new mitochondria are produced and added to the organelle pool for shipping in future NIGHT cycles. If the overall somatic firing rate during DAY exceeded the homeostatic ceiling — meaning the entire neuron was over-recruited — a global downscaling factor is applied to all synapses simultaneously, reducing AMPA counts and release probabilities network-wide. This homeostatic correction is not targeted to any specific synapse; it is a blanket adjustment that restores the neuron's mean excitability without erasing the relative differences between strong and weak synapses. When all queues are empty and all tags are cleared, CREB phosphorylation and CREB activation are reset to false, closing the gene expression program until the next DAY's activity reactivates it.
|
||||||
|
|
||||||
|
### ASTRO — Structural Commit
|
||||||
|
|
||||||
|
The astrocyte's NIGHT work centers on remodeling its physical relationship to each synapse it wraps. For synapses that were validated for LTP during DAY, the astrocyte draws from its ECM protein pool to secrete Glypicans and Thrombospondins, sealing and structurally reinforcing the synaptic environment. It draws from its process extension budget to retract its walls inward — physically tightening the wrap around the synapse. This tightening is itself a slow trace with two consequences: it reduces the rate at which glutamate diffuses away from the cleft, and it raises the tonic D-serine level available to the NMDA receptor. Both changes make the synapse more sensitive to future events, making LTP self-reinforcing. For synapses committed to LTD, the reverse occurs: MMP enzymes dissolve the ECM, D-serine supply is cut to zero, and the astrocyte's process walls extend outward, loosening the diffusion geometry and making future signals less concentrated and less likely to trigger NMDA opening. The freed process extensions are returned to the pool and become available for reallocation to LTP synapses.
|
||||||
|
|
||||||
|
---
|
||||||
|
|
||||||
|
## Key Asymmetries and the Closure Summary
|
||||||
|
|
||||||
|
The perisynaptic distance variable is the one slow trace that amplifies rather than merely reflects the outcome. Because it controls both glutamate diffusion geometry and tonic D-serine availability simultaneously, a synapse that has been potentiated becomes progressively easier to potentiate further, and one that has been depressed becomes progressively harder to rescue — not because of any new signal but because the physical environment was remodeled to favor the existing direction.
|
||||||
|
|
||||||
|
The synaptic tag is the bridge that closes the loop between DAY and NIGHT. It is planted in the NOT_bAP context of DAY when a calcium event meets the tagging threshold, and it is consumed in the NIGHT scope when structural resources are available to fulfill the commit. If the neuromodulatory save signal never arrived during DAY — if dopamine or norepinephrine never validated the event as worth storing — the tag expires at the end of NIGHT without triggering a commit, and the DAY's traces are cleared without structural consequence.
|
||||||
|
|
||||||
|
The budget conservation law closes the entire system: LTP draws from shared pools and passively impoverishes untagged neighbors; LTD returns resources to shared pools and passively enriches them. The total resources in the system do not grow through activity — they are redistributed. The only way to increase total capacity is through NIGHT-scope CREB-driven synthesis and organelle biogenesis, and even that is bounded by the vascular glucose ceiling that the astrocyte cannot exceed regardless of demand. Every behavior in the system therefore occurs within a context that permits it, consumes from a budget that constrains it, and leaves a trace that shifts the probability of the next behavior — and the entire architecture is designed so that no single event, however strong, can permanently commit the system without the conjunction of the right context, the right energy state, and the right neuromodulatory validation.
|
||||||
|
|
||||||
|
---
|
||||||
|
---
|
||||||
|
|
||||||
|
# Pseudocode: Tripartite Synapse — Scope & Context Aware Pseudocode v2
|
||||||
|
|
||||||
---
|
---
|
||||||
|
|
||||||
|
|||||||
Reference in New Issue
Block a user