v10
This commit is contained in:
@@ -0,0 +1,244 @@
|
||||
# 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.
|
||||
Reference in New Issue
Block a user