diff --git a/elements/astrocyte/appunti/tripartite_synapse_full_pseudocode.html b/elements/astrocyte/appunti/tripartite_synapse_full_pseudocode.html new file mode 100644 index 0000000..6cf0272 --- /dev/null +++ b/elements/astrocyte/appunti/tripartite_synapse_full_pseudocode.html @@ -0,0 +1,280 @@ + + +
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postsynapse
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presynapse
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astrocyte
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signal / neuromodulator
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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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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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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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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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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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PKA_activity // downstream of cAMP
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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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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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RRP_pool_capacity // max readily-releasable pool
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VGCC_clustering // Ca²⁺ channels beneath active zone
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perisynaptic_distance // how close astrocyte walls are to synapse
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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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function fire_action_potential(input_freq):
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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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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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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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astro_Ca_local += IP3_cascade(PLC)
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D_serine_release += proportional_to(astro_Ca_local)
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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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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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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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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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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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function short_term_plasticity(input_freq, duration):
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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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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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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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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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phosphorylate(GluA1, site=Ser845)
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GluA1_Ser845_primed = True // lowers CaMKII threshold
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phosphorylate(DARPP32)
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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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LTP_threshold *= (1 / (1 + ACh_level × mAChR_gain))
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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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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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if event_detected and overflow_sensed and context_validated:
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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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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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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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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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return "temporary facilitation only"
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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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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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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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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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else:
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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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function shockwave_lockdown():
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astro_Ca_global = GLOBAL_WAVE // soma-level flood
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release(GABA, ATP) // gel floods postsynapse
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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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function metabolic_loop(Δt):
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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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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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// 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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// LTD: astrocyte moves OUT → looser diffusion barrier
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// → glutamate_clearance_rate ↑ (signal bleeds away faster)
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// → D_serine_tonic_level = 0 (NMDA gate chronically starved)
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// Result: astrocyte amplifies both directions simultaneously
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// potentiation becomes self-reinforcing; depression becomes self-reinforcing
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