Update 2026-06-04-modulation-of-future-behavior.md
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@@ -56,26 +56,26 @@ If the calcium event occurred but the neuromodulatory save signal did not arrive
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The astrocyte's perisynaptic wall distance is the variable that makes both outcomes self-reinforcing rather than merely additive. When it moves inward during potentiation, it concentrates glutamate at the cleft, maintains D-serine near the postsynapse, and tightens the presynaptic feedback loop — making future high-frequency events even more likely to cross the threshold. When it moves outward during depression, it dilutes the signal, starves the NMDA gate, and loosens the presynaptic feedback — making future events even less likely to reach threshold. The astrocyte therefore does not simply mirror what the neurons decide: it actively deepens the valley the synapse has already rolled into, in whichever direction that happens to be.
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## Pseudocode
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# Pseudocode
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[pseudocode](tripartite_synapse_full_pseudocode.html)
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### global state variables
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#### ── Fast (ms–s): wave propagation ─────────────────────────────
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##### Presynapse
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## global state variables
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### ── Fast (ms–s): wave propagation ─────────────────────────────
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#### Presynapse
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pre_Ca_residual // leftover Ca²⁺ between spikes — short-term trace
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vesicle_release_prob // P(0.1–1.0) per docking slot
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RRP_pool // readily-releasable vesicle pool
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reserve_pool // chained vesicles in deep storage
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##### Postsynapse
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#### Postsynapse
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membrane_potential // Vm — depolarization state
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NMDA_Mg_block // bool — mechanical clamp on/off
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post_Ca_amplitude // peak [Ca²⁺] rise in spine
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post_Ca_rise_speed // d(Ca)/dt — fast=LTP signal, slow=LTD signal
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##### Astrocyte
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#### Astrocyte
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glutamate_cleft // [glu] in synaptic cleft
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glutamate_spillover // extrasynaptic [glu] — saturates mGluRs
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astro_Ca_local // IP3-triggered local rise near synapse
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@@ -83,7 +83,7 @@ astro_Ca_global // soma-wide wave — network overload flag
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D_serine_release // gliotransmitter — NMDA co-agonist pulse
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lactate_output // fuel export rate to pre and post
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#### ── Intermediate (s–min): temporary tuning ────────────────────
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### ── Intermediate (s–min): temporary tuning ────────────────────
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mGluR2_3_activation // presynaptic Gi — autoinhibitory brake
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mGluR5_activation // astrocytic Gq — IP3→Ca²⁺→D-serine cascade
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cAMP_level // set by dopamine/NE via Gs → adenylyl cyclase
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@@ -92,7 +92,7 @@ GluA1_Ser845_primed // bool — AMPA insertion threshold lowered by PKA
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DARPP32_phospho // bool — PP1 (LTD phosphatase) silenced by PKA
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CREB_active // bool — structural gene expression enabled
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#### ── Slow (h–weeks): structural architecture ───────────────────
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### ── Slow (h–weeks): structural architecture ───────────────────
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AMPA_count // surface receptors — postsynaptic sensitivity
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spine_volume // physical size of dendritic spine
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active_zone_size // docking slot count
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@@ -103,10 +103,10 @@ ECM_integrity // extracellular matrix density
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D_serine_tonic_level // baseline co-agonist supply (sustained)
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glutamate_clearance_rate // EAAT transporter density
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#### fast time scale — wave propagation (ms → s)
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### fast time scale — wave propagation (ms → s)
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function fire_action_potential(input_freq):
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##### Presynapse: launch wavefront
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#### Presynapse: launch wavefront
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pre_Ca_residual += spike_influx(input_freq)
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pre_Ca_residual *= decay(τ ≈ 100ms) // fades unless spikes keep arriving
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vesicle_release_prob *= facilitation(pre_Ca_residual)
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@@ -114,7 +114,7 @@ released_vesicles = binomial(RRP_pool, vesicle_release_prob)
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glutamate_cleft = released_vesicles × quantal_content
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RRP_pool -= released_vesicles
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##### Astrocyte: overflow sensing and co-agonist release
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#### Astrocyte: overflow sensing and co-agonist release
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glutamate_spillover = extrasynaptic_diffusion(glutamate_cleft)
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if glutamate_spillover > spillover_threshold:
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mGluR5_activation = True // Gq arm → IP3 → Ca²⁺ → D-serine
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@@ -124,46 +124,46 @@ mGluR2_3_activation = True // Gi arm → brake presynapse
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cAMP_level -= Gi_inhibition(adenylyl_cyclase)
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vesicle_release_prob -= VGCC_suppression() // autoinhibitory brake
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##### Astrocyte: check for network overload
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#### Astrocyte: check for network overload
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astro_Ca_global = soma_wave(astro_Ca_local > OVERLOAD_threshold)
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if astro_Ca_global: trigger(shockwave_lockdown)
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##### Postsynapse: wavefront strikes resonator
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#### Postsynapse: wavefront strikes resonator
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AMPA_current = glutamate_cleft × AMPA_count
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membrane_potential += AMPA_current
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##### NMDA gate: coincidence check
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#### NMDA gate: coincidence check
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if membrane_potential > -40mV and D_serine_release > threshold:
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NMDA_Mg_block = False // Mg²⁺ ejected
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post_Ca_amplitude += NMDA_influx(glutamate_cleft)
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post_Ca_rise_speed = d(post_Ca_amplitude) / dt
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##### Astrocyte: vacuum trailing echoes + fuel pipeline
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#### Astrocyte: vacuum trailing echoes + fuel pipeline
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glutamate_cleft -= glutamate_clearance_rate × Δt
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lactate_output += glycolysis_rate(glutamate_clearance_rate)
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membrane_potential restored by NaK_ATPase(lactate_output)
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RRP_pool refilled by VATPase(lactate_output)
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#### intermediate time scale — temporary tuning (s → min)
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### intermediate time scale — temporary tuning (s → min)
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function short_term_plasticity(input_freq, duration):
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##### Presynapse: facilitate or depress based on Ca²⁺ history
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#### Presynapse: facilitate or depress based on Ca²⁺ history
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if input_freq > 20Hz:
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vesicle_release_prob *= 1.3 // residual Ca²⁺ primes launchpad
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mobilize(reserve_pool → RRP_pool) // break storage chains
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elif input_freq < 5Hz:
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vesicle_release_prob *= 0.7 // RRP depleted faster than refill
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##### Postsynapse: NMDA gate primed if frequency sustained
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#### Postsynapse: NMDA gate primed if frequency sustained
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if input_freq >= 50Hz and duration > 1s:
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NMDA_Mg_block = False // sustained depolarization
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post_Ca_amplitude accumulates // early-LTP signal rises
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##### Astrocyte: sustained volume → escalate co-agonist
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#### Astrocyte: sustained volume → escalate co-agonist
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if astro_Ca_local > local_threshold:
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D_serine_release += gliotransmitter_pulse() // widens NMDA window
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##### Neuromodulators: set context gate via Gs protein
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#### Neuromodulators: set context gate via Gs protein
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if dopamine_level > D1_threshold or NE_level > β_threshold:
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cAMP_level += Gs_activation(adenylyl_cyclase)
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PKA_activity = proportional_to(cAMP_level)
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@@ -174,74 +174,74 @@ DARPP32_phospho = True // silences PP1 — blocks LTD
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translocate(PKA → nucleus) → phosphorylate(CREB)
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CREB_active = True // enables structural gene expression
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##### Acetylcholine: lower LTP threshold globally
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#### Acetylcholine: lower LTP threshold globally
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LTP_threshold *= (1 / (1 + ACh_level × mAChR_gain))
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#### slow time scale — structural commit (h → weeks)
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### slow time scale — structural commit (h → weeks)
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function commit_to_structural_change():
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##### Hierarchical filter: three conditions must align
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#### Hierarchical filter: three conditions must align
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event_detected = post_Ca_amplitude > Ca_HIGH // layer 1: did something happen?
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overflow_sensed = mGluR5_activation == True // layer 2: was it excessive?
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context_validated = DARPP32_phospho and GluA1_Ser845_primed // layer 3: worth saving?
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##### ── Branch 1: LTP — potentiation ──────────────────────────────
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#### ── Branch 1: LTP — potentiation ──────────────────────────────
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if event_detected and overflow_sensed and context_validated:
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###### Postsynapse: anchor receptors, enlarge spine
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##### Postsynapse: anchor receptors, enlarge spine
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activate(CaMKII)
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AMPA_count += receptor_insertion(CaMKII, GluA1_Ser845_primed)
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spine_volume *= 1.5
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###### Presynapse: expand launchpad, increase output reliability
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##### Presynapse: expand launchpad, increase output reliability
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active_zone_size *= 1.4 // more docking slots
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RRP_pool_capacity += pool_expansion(active_zone_size)
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VGCC_clustering += cluster_beneath_AZ() // tighter Ca²⁺ coupling
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vesicle_release_prob += 0.1 // driven by VGCC clustering
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###### Astrocyte: seal and insulate the channel
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##### Astrocyte: seal and insulate the channel
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perisynaptic_distance -= process_retraction() // walls move IN → tighter wrap
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ECM_integrity += secrete(Glypicans, Thrombospondins)
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D_serine_tonic_level += upregulate_synthesis() // sustained NMDA priming
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glutamate_clearance_rate *= 0.85 // tighter wrap → slower diffusion away
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return "potentiated"
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##### ── Branch 2: temporary only — Ca²⁺ rose, no save signal ─────
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#### ── Branch 2: temporary only — Ca²⁺ rose, no save signal ─────
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elif event_detected and not context_validated:
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AMPA_count += transient_insertion() // early-LTP only — reverses in minutes
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vesicle_release_prob += transient_facilitation()
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###### No astrocyte structural change
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##### No astrocyte structural change
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return "temporary facilitation only"
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##### ── Branch 3: LTD — active forgetting ─────────────────────────
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#### ── Branch 3: LTD — active forgetting ─────────────────────────
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elif event_detected and not overflow_sensed and not context_validated:
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###### Postsynapse: internalize receptors, shrink spine
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##### Postsynapse: internalize receptors, shrink spine
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activate(PP1)
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AMPA_count -= receptor_internalization(PP1)
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spine_volume *= 0.7
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###### Presynapse: dismantle launchpad
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##### Presynapse: dismantle launchpad
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active_zone_size -= docking_slot_removal()
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RRP_pool_capacity -= pool_contraction()
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VGCC_clustering -= scatter_VGCCs() // decouple Ca²⁺ from AZ
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vesicle_release_prob *= 0.6
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###### Astrocyte: dissolve matrix, pull away, cut support
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##### Astrocyte: dissolve matrix, pull away, cut support
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ECM_integrity -= secrete(MMPs) // molecular scissors
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D_serine_tonic_level = 0 // co-agonist supply cut
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perisynaptic_distance += process_extension() // walls move OUT → loose wrap
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glutamate_clearance_rate *= 1.2 // looser wrap → faster spillover
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return "depressed"
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##### ── Branch 4: baseline ────────────────────────────────────────
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#### ── Branch 4: baseline ────────────────────────────────────────
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else:
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###### All structural variables unchanged — system holds current state
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##### All structural variables unchanged — system holds current state
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return "baseline — no change"
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##### special case — shockwave lockdown (>100Hz uncoordinated)
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#### special case — shockwave lockdown (>100Hz uncoordinated)
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function shockwave_lockdown():
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astro_Ca_global = GLOBAL_WAVE // soma-level flood
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@@ -250,18 +250,19 @@ AMPA_count -= mass_internalization()
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membrane_potential = HYPERPOLARIZED
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cluster(VGCC → beneath_active_zone) // ensures signal survives chaos
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##### energy supply chain — metabolic gating (continuous)
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#### energy supply chain — metabolic gating (continuous)
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function metabolic_loop(Δt):
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###### Astrocyte: glucose → lactate pipeline
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##### Astrocyte: glucose → lactate pipeline
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glucose_uptake = blood_capillary_supply()
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lactate_output = glycolysis(glucose_uptake, glutamate_clearance_rate)
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lactate_output *= load_factor(glutamate_clearance_rate)
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###### Pre + post absorb lactate → power their pumps
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##### Pre + post absorb lactate → power their pumps
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RRP_pool refill rate ∝ VATPase(lactate_output)
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membrane_potential reset ∝ NaK_ATPase(lactate_output)
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##### key asymmetry — perisynaptic distance is bidirectional
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#### key asymmetry — perisynaptic distance is bidirectional
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// LTP: astrocyte moves IN → tighter diffusion barrier
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// → glutamate_clearance_rate ↓ (signal contained, not diluted)
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// → D_serine_tonic_level ↑ (NMDA gate chronically primed)
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@@ -274,7 +275,7 @@ membrane_potential reset ∝ NaK_ATPase(lactate_output)
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// potentiation becomes self-reinforcing; depression becomes self-reinforcing
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## Neuromodulators
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# Neuromodulators
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These are produced by small, anatomically concentrated nuclei that broadcast widely across the brain:
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@@ -282,14 +283,14 @@ dopamine_level // "save button" — validates LTP
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norepinephrine_level // arousal / signal-to-noise gain
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acetylcholine_level // attention — lowers LTP threshold
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### Dopamine
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## Dopamine
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Dopamine is produced primarily by neurons in the Substantia Nigra pars compacta (projecting to the striatum, relevant for motor learning and habit formation) and the Ventral Tegmental Area (VTA) (projecting to the prefrontal cortex and limbic system via the mesolimbic and mesocortical pathways, relevant for reward, motivation, and the "save button" function in your model).
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### Norepinephrine
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## Norepinephrine
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Norepinephrine is produced almost exclusively by the Locus Coeruleus, a tiny nucleus in the brainstem pons. Despite its small size it projects diffusely across virtually the entire brain — cortex, hippocampus, cerebellum, spinal cord. It's essentially the brain's arousal and signal-to-noise broadcaster, firing tonically at low rates during calm wakefulness and phasically during novel or stressful events.
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### Acetylcholine
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## Acetylcholine
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Acetylcholine has two main sources: the basal forebrain nuclei (including the nucleus basalis of Meynert) projecting to the cortex and hippocampus — relevant for attention and learning gating — and the medial septum projecting specifically to the hippocampus, where it strongly modulates theta rhythms and memory encoding.
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What's striking in the context of your model is that all three systems share the same architectural logic: a tiny, localized cell population broadcasts a global contextual signal that shifts the operational threshold of millions of synapses simultaneously — none of them carrying specific content, all of them modulating how content gets written.
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