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Tripartite Synapse — Biological Reference (companion to v10 pseudocode)

This document explains what each variable and behavior in tripartite_synapse_v10_pseudocode.md conflates biologically. The pseudocode aggregates many molecular details into single variables for clarity; here each aggregation is unpacked. Read the pseudocode for the logic; read this when you need to know what a variable physically represents.

The three synaptic components and their support structures

A SYNAPSE is composed of three first-class components:

PRE — presynaptic bouton (the axon's terminal at this synapse)
POST — postsynaptic spine (the dendrite's terminal at this synapse)
ASTRO — astrosynapse, the perisynaptic astrocytic process (the astrocyte's terminal)

Each has an upstream support structure that supplies it:

AXON supplies PRE (transmission + transport from soma)
DEND supplies POST (integration + transport from soma)
the astrocyte cell body supplies ASTRO (energy + ECM material)
SOMA is the integrating center and the root of neuronal material

The compartment analogy: AXON:PRE = DEND:POST = astrocyte-body:ASTRO = supply line : terminal.

Resource variables

DAY budget (one per component)

Aggregates fast energy AND fast consumables — everything needed to run moment-to-moment.

pre_budget — ATP for VGCC gating, vesicle fusion (SNARE), VATPase vesicle refill, plus fast consumables: vesicle membrane lipids, synaptotagmin recycling.
post_budget — ATP for the NaK pump (membrane reset after current), NMDA current handling, plus fast actin monomers for transient spine changes and receptor-recycling lipids.
dend_budget — ATP for bAP propagation (NaK reset along branch), local translation (ribosome running cost), SERCA Ca²⁺ resequestration, plus fast mRNA consumed by translation.
soma_budget — ATP for AP generation (Na⁺/K⁺ currents + NaK reset), CREB phosphorylation, nuclear Ca²⁺ handling, plus shipping running costs.
axon_budget — ATP for AP propagation at nodes of Ranvier, kinesin/dynein motor running cost, fast myelin maintenance.
astro_central_budget — ATP from glycolysis at the astrocyte cell body; funds EAAT clearance, serine→D-serine synthesis, lactate export, fast process motility.

astro_lactate[i]

Lactate exported from the astrocyte cell body to synapse i. Biologically: glucose → (glycolysis) → lactate, released into extracellular space, absorbed by neuronal MCT2 transporters, converted to pyruvate → TCA → ATP in the neuron's mitochondria. The astrocyte is the primary fast-energy supplier to pre, post, and dend.

NIGHT energy (one per component) — NOT recoverable

ATP for structural assembly. Distinct from DAY budget because it is spent on building, and the work of assembly is thermodynamically gone once done (cannot be recovered by disassembly).

pre_energy: RIM/Munc13 incorporation, VGCC clustering.
post_energy: CaMKII anchoring, actin polymerization, PSD scaffold remodeling.
dend_energy: mitochondria incorporation, cytoskeletal reinforcement.
soma_energy: ribosome biogenesis, ion-channel incorporation.
axon_energy: myelination, microtubule stabilization.
astro_energy: process retraction, ECM secretion, racemase upregulation.

NIGHT material (one per component) — RECOVERABLE

Slow structural proteins. Recoverable because disassembly (LTD) returns the proteins to a reusable pool (ubiquitin-proteasome → amino acids; internalized receptors → endosomal reserve).

soma_material (root) — all neuronal structural proteins from CREB-driven synthesis: AMPA subunits, PSD scaffold, AZ scaffold, mRNA transcripts (Arc, BDNF), organelles.
dend_material — from soma: Arc/plasticity mRNA, mitochondria, cytoskeletal proteins, AMPA subunits in transit to spines.
post_material — from dend: AMPA receptor subunits (GluA1/2), PSD scaffold (PSD-95, SHANK, Homer), structural actin, CaMKII.
axon_material — from soma: kinesin/dynein motors, microtubule components, myelin proteins.
pre_material — from axon: RIM, Munc13, VGCC subunits, structural vesicle proteins.
astro_material (root: astrocyte cell body) — EAAT proteins, serine racemase, ECM proteins (Glypicans, Thrombospondins), process cytoskeleton.

Why energy and material are separate in NIGHT but combined in DAY: during DAY both are fast consumables replenished on the same timescale, so one budget variable suffices. During NIGHT they diverge — material is recoverable after LTD, energy is not — so they must be two variables. This asymmetry (material returns to the pool, energy is gone) is what makes one synapse's depression genuinely fund another's potentiation.

Structural variables (strength ceilings — written in NIGHT)

Each aggregates several correlated structural properties into one capacity.

pre_structure — active zone capacity: slot_ceiling (number of vesicle docking slots) + VGCC_coupling (Ca²⁺-channel proximity to slots, sets release efficiency) + refill_ceiling (max RRP replenishment rate).
post_structure — spine sensitivity capacity: slot_ceiling (number of PSD anchoring slots for AMPA) + spine_volume (local reserve and actin machinery) + reserve_ceiling (endosomal AMPA pool size).
dend_structure — branch capacity: bAP_fidelity(position) (mitochondrial density sets propagation strength, attenuates with distance) + translation_ceiling (local mRNA capacity) + transport_speed (cytoskeletal integrity).
soma_structure — somatic output capacity: baseline_threshold (inverse: ion-channel density at axon initial segment) + AP_reliability (Na⁺ channel density) + synthesis_ceiling (ribosome density + CREB machinery).
axon_structure — axonal capacity: propagation reliability (myelination density) + transport_ceiling (motor density + microtubule integrity) + mitochondrial density.
astro_structure — astrosynaptic environmental capacity: perisynaptic_distance⁻¹ (wall proximity — closer = more glutamate contained) + EAAT_density (clearance ceiling) + Dserine_tonic (baseline co-agonist) + ECM_integrity. Self-reinforcing both directions: tighter wrap + more tonic D-serine make future potentiation easier; looser wrap + zero tonic D-serine make future depression easier.

Budget ceilings (endurance ceilings — written in NIGHT)

{component}_budget_ceiling — the maximum fuel the component can hold / the maximum duration of sustained behavior. Biologically: mitochondrial density and local fuel-storage capacity. Built by activity-driven mitochondrial biogenesis; lost by mitophagy when idle. Parallel to structure: structure is strength capacity, budget_ceiling is endurance capacity.

Trace variables

fast_trace (one per component) — DAY only, decays automatically

The local record of recent activity that biases the next behavior.

pre_fast_trace — residual presynaptic Ca²⁺ after spikes (τ≈100ms). Biases NT release (facilitation) and provides tagging eligibility.
post_fast_trace — spine Ca²⁺ amplitude × rise-speed (τ≈tens ms). Encodes the LTP-vs-LTD instruction (fast rise → CaMKII → potentiation; slow rise → phosphatase → depression).
dend_fast_trace — branch Ca²⁺ from bAP + spine spillover (τ≈300ms). Integrates branch co-activity.
soma_fast_trace — nuclear Ca²⁺ from each AP (τ≈seconds). Drives toward CREB activation.
axon_fast_trace — propagation load (τ≈seconds). High load → Na⁺ inactivation at branch points → propagation failure (this is axonal short-term depression).
astro_fast_trace — perisynaptic Ca²⁺ from mGluR5 activation by glutamate spillover (τ≈seconds). Drives D-serine release.

soma timing traces (emergent refractory + adaptation + alignment)

soma_Na_inactivation (τ≈ms) — sodium-channel inactivation after an AP. Its recovery IS the refractory period (emergent, not a hardcoded timer). High → absolute refractory; decaying → relative refractory; recovered → normal.
soma_adaptation (τ≈100s of ms) — slow K⁺ channel (SK/M-type) activation accumulating over a spike train, raising threshold. This is spike-frequency adaptation.
soma_refractory_alignment — deposited when a suprathreshold input arrives during refractoriness (a missed coincidence). Speeds future recovery so the soma aligns to its input rhythm. Bottom-up: no rhythm is represented; alignment emerges from accumulated local mismatches and decays when mismatches stop (self-limiting).

possible_tag (one per component) — intermediate, τ≈s–min

Graded accumulation of tagging eligibility. For POST, this is the CANDIDATE tag lifetime.

endurance_need (one per component) — intermediate, τ≈s–min

Deposited when budget depletion interrupts a behavior that was on a LOCALLY successful trajectory. Records that fuel — not structure, not significance — was the binding constraint on a forming success. Requires NO dopamine (homeostatic, not associative). Local success proxy per component (each uses only its own state + arrived signals):

PRE: own fast_trace high (was releasing strongly), optionally amplified by retrograde messenger (endocannabinoid / NO / BDNF) that has arrived.
POST: own Ca²⁺ climbing toward tagging threshold (naturally local).
DEND: own branch strongly active (high branch voltage/Ca²⁺) when propagation fell short.
SOMA: own nuclear Ca²⁺ climbing toward CREB.
AXON: own propagation load high (was carrying a strong train).
ASTRO: own local glutamate/Ca²⁺ high (was under heavy clearance/D-serine demand).

tag (one per component) — DAY→NIGHT bridge, τ≈hours

The validated record of significance that survives to NIGHT and gates strength commits. Formed by coincidence of local eligibility + non-local validation (dopamine). POST is special — two-phase, three coincidences:

CANDIDATE: local Ca²⁺ above threshold + astrosynapse D-serine present (coincidence 1).
amplified when bAP confirms soma fired (coincidence 2).
STABLE: CANDIDATE + dopamine within stabilization window (coincidence 3). Biologically: early CaMKII creates a labile tag (early-LTP); PKA driven by dopamine via D1R stabilizes it (late-LTP). Without dopamine, the candidate degrades — early-LTP reverses.

Behaviors — biological meaning

PRE | AP — neurotransmitter release

NT_flux = RRP × sat(pre_fast_trace, K_release) models continuous NT release proportional to the readily-releasable pool and a saturating Ca²⁺ drive (synaptotagmin's cooperative Ca²⁺ sensitivity, simplified to a saturating curve). RRP depletes as released (short-term depression as a consequence) and refills via VATPase (energy-throttled, so low budget deepens depression). The mGluR2/3 brake is presynaptic autoinhibition by spillover (Gi → reduced VGCC opening).

POST | NOT_bAP — three calcium sources, two plasticity cases

Source 1 (AMPA): glutamate opens AMPA → depolarizing current + small Ca²⁺; the depolarization begins ejecting the NMDA Mg²⁺ block.
Source 2 (NMDA): if depolarized enough (Mg²⁺ ejected) AND D-serine present (astrocyte co-agonist) AND glutamate bound → large Ca²⁺ influx. This is the coincidence detector.
Source 3 (bAP, separate context): back-propagating AP adds depolarization + Ca²⁺, amplifying an existing signal supralinearly.
Case 1 (STP): high Ca²⁺ drives AMPA receptors from the local reserve to the surface, bounded by the anchoring-slot ceiling. Fast, reversible, NO dopamine. When Ca²⁺ falls, receptors drift back — short-term depression as a passive consequence, never signaled.
Case 2 (LTP tag): high Ca²⁺ + (later) dopamine sets the tag that NIGHT uses to raise the slot ceiling. NIGHT builds slots; DAY fills them.

DEND | bAP — bidirectional signaling

Propagates the bAP from soma toward spines (fidelity attenuates with distance — distal spines get weaker confirmation, are harder to potentiate) and integrates spine signals toward the soma.

SOMA | AP — integration, firing, emergent timing

Fires when integrated branch input exceeds a threshold that is the baseline (from structure) raised by adaptation and modulated by neuromodulators, gated by the emergent refractory state. Each AP deposits three traces (inactivation → refractory, adaptation → threshold rise, nuclear Ca²⁺ → plasticity). The soma is the coincidence detector at the cellular scale (nuclear Ca²⁺ + dopamine → CREB), and the production bottleneck: its tag gates how much material all downstream components get in NIGHT.

AXON | AP — reliable propagation with frequency-dependent failure

Propagation reliability is set by myelination and degraded by high-frequency load (Na⁺ inactivation at branch points = axonal STD). The axon also transports material to boutons and sets the timescale of presynaptic structural commits.

ASTRO | CONTINUOUS — gatekeeper and energy hub

Clears glutamate (EAAT), supplies D-serine (the NMDA co-agonist that gates postsynaptic LTP), and distributes lactate to the territory by demand-weighting (active synapses generating more clearance load pull more fuel; slow synapses get less). The same spillover that excites the astrocyte (mGluR5 → Ca²⁺ → D-serine) also brakes the presynapse (mGluR2/3 → Gi) — one signal, opposite effects via different receptors. The astrocyte is the energy root and the gain control of the whole synapse.

NIGHT operations — biological meaning

Step 1 (replenish/distribute): overnight protein synthesis peaks (CREB-driven, gated by soma_tag — corresponds to slow-wave-sleep replay). Soma material flows to branches/axon then spines/boutons; astrocyte material flows to astrosynapses, tag-weighted.
Step 2 (strength commits): tagged components build structure — more slots, tighter coupling, tighter astrosynaptic wrap. Coherence bonus when pre+post+astro all tagged (the whole synapse agrees). astro_structure self-reinforces.
Step 2b (endurance commits): components with high endurance_need build budget_ceiling — mitochondrial biogenesis. Competes with step 2 for the same material/energy.
Step 3 (passive decay): both ceilings decay; maintenance from the remaining pool resists decay only where sufficient. Depotentiation and endurance-loss are both by neglect — no signal weakens anything; unmaintained capacity simply drifts down. Recovered material (not energy) returns to pools.
Step 4 (homeostatic scaling): if the soma fired too much overall, all synapses scale down proportionally (sleep-associated global downscaling), preserving relative differences.
Step 5 (clear traces): fast traces, possible tags, endurance needs, and soma timing traces reset; tags below expiry clear, above-expiry tags carry forward (multi-night consolidation); structure and budget_ceiling persist.

Shockwave lockdown

Emergency global astrocytic Ca²⁺ wave → GABA + ATP release → mass AMPA internalization and hyperpolarization. Bypasses budget gates. A circuit breaker against runaway excitation.

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