varie
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@@ -103,39 +103,81 @@ that neighbours compete for.
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## PRE
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```
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// Backward messages from POST (computed by POST from its own local state, read here):
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// retro_NO (+) : POST responded — release reached a responsive target
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// retro_eCB (−) : POST over-driven — suppress release (DSE)
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// PRE reads these as arrived signals; it never reads POST's internal state.
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// ─── PRESYNAPSE EXTERNAL INTERFACE ────────────────────────────────────────
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// PRE computes locally. Everything below crosses its boundary as a signal it
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// emits or a resource/signal it receives. It never reads another component's state.
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//
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// OUTPUT (PRE writes; others read)
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// glutamate → POST, ASTRO forward transmitter; ASTRO clears it
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//
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// RESOURCES IN (others write; PRE reads in NOT_AP)
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// astro_lactate[syn] ← ASTRO primary fast fuel → pre_budget
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// axon_ship_pre ← AXON secondary fuel → pre_budget
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// ship(axon_budget → pre_budget, gap_to(pre))
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// pre_material ← AXON (NIGHT) AZ proteins (RIM, Munc13, VGCC subunits)
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// pre_energy ← SOMA (NIGHT) assembly ATP for active-zone construction
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//
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// BACKWARD MESSAGES IN (POST writes from its own state; PRE reads)
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// retro_NO (+) ← POST "release reached a responsive target" → endurance
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// retro_eCB (−) ← POST DSE: "over-driven, release less" → brake
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//
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// CLEFT SELF-FEEDBACK (PRE reads the channel it writes)
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// glutamate ← cleft spillover autoreceptor brake (mGluR2/3 on PRE)
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//
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// ORGANISM BROADCAST IN (external; arrives as a local level)
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// dopamine ← VTA gates pre_tag (the non-local coincidence)
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// NE, ACh ← LC, basal excitability/threshold context
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//
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// OWN STRUCTURE (written NIGHT, read DAY)
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// pre_structure slot_ceiling, VGCC_coupling, refill_ceiling
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// pre_budget_ceiling endurance ceiling (bounds replenishment)
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//
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// EMERGENCY
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// shockwave_lockdown ← ASTRO global Ca²⁺ wave overrides PRE
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// ──────────────────────────────────────────────────────────────────────────
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DAY | AP:
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// SENSE — deposit fast trace (residual Ca²⁺ from this spike; also drives release)
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pre_fast_trace += spike_Ca(input_freq)
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// BEHAVE — release, or fail if depleted
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if pre_budget < release_cost:
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suppress(NT_flux)
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// interrupted LOCAL success: I was releasing strongly (own fast_trace),
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// confirmed by retro_NO that POST actually responded
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// EVALUATE (endurance) — interrupted LOCAL success, confirmed by retro_NO
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if pre_fast_trace > traj_thr:
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pre_endurance_need += pre_fast_trace × (1 + retro_NO_local)
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exit
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pre_fast_trace += spike_Ca(input_freq); pre_fast_trace *= decay(100ms)
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drive = sat(pre_fast_trace, K_release) × (1 - retro_eCB_local) // DSE brake from POST
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drive = sat(pre_fast_trace, K_release) × (1 - retro_eCB_local) // received DSE brake
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if RRP > 0:
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NT_flux = RRP × drive
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glutamate += NT_flux·Δt; RRP -= NT_flux·Δt; pre_budget -= NT_flux·fusion_cost
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if glutamate > spillover: drive *= brake // autoreceptor/astro brake (output)
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// NO fill here — AP only depletes RRP; recovery happens in NOT_AP
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// (sustained high-frequency firing therefore deepens short-term depression)
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NT_flux = RRP × drive
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// EMIT — glutamate into cleft (read by POST, ASTRO)
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glutamate += NT_flux·Δt
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RRP -= NT_flux·Δt; pre_budget -= NT_flux·fusion_cost
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if glutamate > spillover: drive *= brake // own-cleft autoreceptor brake
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// no RECOVER here — RRP refills in NOT_AP; high-frequency firing depletes
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// faster than it recovers → short-term depression deepens
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DAY | NOT_AP:
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pre_fast_trace *= decay(100ms); pre_endurance_need *= decay(min)
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retro_NO_local = retro_NO; retro_NO *= decay(s) // receive + channel clears (NO short-lived)
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retro_eCB_local = retro_eCB; retro_eCB *= decay(s) // receive + channel clears
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refill(pre from astro_lactate[syn] + axon_ship_pre) // contested: lactate + shipment
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fill(RRP, pre_structure.slot_ceiling, pre_structure.refill_ceiling, vatpase_cost, pre_budget) // private reserve
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// RECEIVE — latch arrived backward messages; replenish budget (contested supply)
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retro_NO_local = retro_NO
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retro_eCB_local = retro_eCB
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refill(pre from astro_lactate[syn] + axon_ship_pre)
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// RECOVER — refill RRP from private reserve toward its ceiling
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fill(RRP, pre_structure.slot_ceiling, pre_structure.refill_ceiling, vatpase_cost, pre_budget)
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// EVALUATE (strength) — eligibility → possible_tag → tag (needs dopamine)
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if pre_fast_trace > elig: pre_possible_tag += pre_fast_trace
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pre_possible_tag *= decay(s); dopamine *= decay(ms)
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if dopamine > dop_thr and pre_possible_tag > tag_thr:
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pre_tag += dopamine × pre_possible_tag
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pre_tag *= decay(hr)
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// DECAY — all traces and channels recede, closing their windows
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pre_fast_trace *= decay(100ms)
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pre_possible_tag *= decay(s)
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pre_endurance_need *= decay(min)
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pre_tag *= decay(hr)
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dopamine *= decay(ms) // broadcast transient fades
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retro_NO *= decay(s); retro_eCB *= decay(s) // backward channels clear
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```
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---
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@@ -80,53 +80,28 @@ MAIN
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snippet:
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// *AP
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@: ACCUMULATOR [ snippet: NTreleaseLow, eventuality: active 12x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: NTreleaseMedium, rf: active 9x ]
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@: ACCUMULATOR [ snippet: NTreleaseHigh, rf: active 6x ]
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@: ACCUMULATOR [ snippet: NTreleaseLow, event: active 12x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: NTreleaseMedium, event: active 9x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: NTreleaseHigh, event: active 6x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: TracesAccLow, rf: active 3x ]
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@: ACCUMULATOR [ snippet: TracesAccMedium, rf: active 6x ]
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@: ACCUMULATOR [ snippet: TracesAccHigh, rf: active 10x ]
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@: ACCUMULATOR [ snippet: TracesAccLow, event: active 3x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: TracesAccMedium, event: active 6x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: TracesAccHigh, event: active 10x, cost: active 3x ]
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// NOT *AP
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@: ACCUMULATOR [ snippet: eCBClearenceMedium, rf: active 24x ]
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@: ACCUMULATOR [ snippet: eCBClearenceLow, rf: active 48x ]
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@: ACCUMULATOR [ snippet: eCBClearenceMedium, event: active 24x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: eCBClearenceLow, event: active 48x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: RPShuttleLow, rf: active 24x ]
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@: ACCUMULATOR [ snippet: RPShuttleMedium, rf: active 48x ]
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@: ACCUMULATOR [ snippet: RPShuttleLow, event: active 24x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: RPShuttleMedium, event: active 48x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: RefillGlutamine, rf: active 24x ]
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@: ACCUMULATOR [ snippet: RefillGlutamine, event: active 24x, cost: active 3x ]
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@: ACCUMULATOR [ snippet: TracesClearance, rf: active 30x ]
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@: ACCUMULATOR [ snippet: TracesClearance, event: active 30x, cost: active 3x ]
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```
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**Tubs:**
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- **\_Ca2**: Calcium Ion entering the Presynapse when VCGG open that influence NT release. Normally returns to ~0 between spikes; stays elevated when pumps fail. They are key to check the concentration, release NT and modulation
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- **\_Rrp**: Readily Releasable Pool: The Readily Releasable Pool consists of the vesicles that are "docked" and "primed" at the active zone of the synapse. This pool is very small (usually only about 0.5% to 5% of total vesicles) and can be exhausted quickly during high-frequency firing, leading to "short-term depression" of the signal. Here we consider them as NT ready to be released.
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- **\_Rp**: Reserve Pool: The bulk of the vesicles held further back in the terminal, often tethered by a protein called synapsin. These are only mobilized during intense, prolonged stimulation. This makes up the vast majority of the vesicles (up to 80% or 90%). Here we consider them NT in reserve that can be transfered to RRP and created using Glutamine from Astorcyte.
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- **\_NT**: Neuro Transmitter, released in the synapse by the vescicles. The release increses NT and decreases RRP
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- **\_CaTracesXXX**: sono le tracce di permanenza della concentrazione di Ca2. Servono alla modulazione (TUN)
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- **\_eCB**: retrograde signal updates from postsynapsis (postsynaptic input)
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#### *AP
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Il rilascio di NT lo facciamo nel contesto di AP. Biologicamente dovrebbe avvenire solo in base alle concentrazioni, quindi anche al difuori degli AP.
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RF di interacting deve essere MOLTO piu' basso di un RF di AP. In maniera da essere attivo varie volte nel contesto di un episodio di AP. Il che ha senso perche' un AP e' SOMA ad un tempo piu' alto che i comportamenti di PRE. Questo poi per permettere la diversa contestualizzazione degli episodi di NTrelease, a piu' o meno alta velocita'.
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Non consideriamo le vesicles come liberate, ma direttamente gli NT. Questo permette di gestire la quantita' rilasciata di NT, invece di gestire un numero di vescicles. Nella realta' ciascuna vesicle contiene migliaia di NT. Qui mettiamo un floor a questo tipo di comprensione.
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Ci sono 4 casi che dipendono da RRP, Ca2 e indirettamente da concentrazione di NT nella SYN che diventa mGLur che limita in VGCC l'entrata di Ca2. L'idea e' che la quantita' di RRP sia il driver principale. Gli NT liberati sono di piu' al crescere di RRP e Ca2 e di meno (indirettamente) al crescere della concentrazione di NT gia' liberati nella SYN. Gli NT nella sinapsi fanno da moderazione alla ulteriore liberazione di NT, ma non bloccano mai totalmente. NT suppression only matters when everything else is already at maximum, which is exactly the biological purpose: it prevents runaway release during peak activity, not during moderate activity.
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---
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NT empty. Qui siamo contestualizzati se Ca2 full, il che dovrebbe significare indirettamente che non ci sono NT nella SYN.
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In tutti i casi di NT
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##### NTreleaseLow
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```Gen
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@@ -177,7 +152,7 @@ Serve a:
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- dare la velocita' al trasporto di vesicles da RP a RRP, anche se non avendo ancora compreso \_ATP, la velocita' non cambia molto la sostanza.
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- le tracce vengono eliminate quando il neurone e' in pausa, lontano da uno spike train, *TunPossible
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- Abbiamo 3 tracce, high, medium and low. Andiamo a verificare una combinazione di queste per fare la modulazione
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- RF e' a 10, questo dovrebbe essere un RF di campionamento durante *AP context che dovremmo assicurarci sia tipo 100. Il che implicherebbe 10 campionamenti.
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- event e' a 10, questo dovrebbe essere un event di campionamento durante *AP context che dovremmo assicurarci sia tipo 100. Il che implicherebbe 10 campionamenti.
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- The biological meaning is that a synapse that has just been through a burst is primed for fast recovery — the molecular machinery for vesicle docking is already engaged, calcium-dependent priming factors are still elevated, and the system is in a ready state. A synapse that has been silent for several seconds has cooled down and replenishes slowly.
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- So after one second of silence CaTrace has fallen to ~37% of its peak value, after two seconds to ~14%, after three seconds to ~5%. It asymptotes toward zero but never exactly reaches it. Between spikes, Ca2 falls toward zero as the pumps clear it. The result is that CaTrace encodes not the instantaneous calcium level but the recent history of calcium activity — a smoothed, time-averaged measure of how active the synapse has been over the past one to two seconds.
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@@ -224,7 +199,7 @@ Ca2TracesAccumulationHigh
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eCB dipende da POST. Tende a modulare l'entrata di Ca2 degli VGCC.
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Qui non facciamo un flush di eCB, riduciamo ogni mezzo secondo (context) di un RF di questo episodio.
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Qui non facciamo un flush di eCB, riduciamo ogni mezzo secondo (context) di un event di questo episodio.
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```Gen
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eCBClearance: ( active: 24x ) # Slow
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@@ -363,13 +338,13 @@ TUN_VGCC
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snippet:
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// *TunPossible
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@: CONTEXTOR [ snippet: VgccCheck, rf: active 60x ]
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@: CONTEXTOR [ snippet: VgccCheck, event: active 60x ]
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// *VcggIncrease
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@: ACCUMULATOR [ snippet: VcggIncrease, rf:active 10x ]
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@: ACCUMULATOR [ snippet: VcggIncrease, event:active 10x ]
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// *VcggDecrease
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@: ACCUMULATOR [ snippet: VcggDecrease, rf:active 10x ]
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@: ACCUMULATOR [ snippet: VcggDecrease, event:active 10x ]
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```
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#### *TunPossible
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@@ -433,18 +408,18 @@ DEV_TUBS
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snippet:
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# *fixed
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@: CONTEXTOR [ snippet: Ca2Check, rf: active 60x ]
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@: CONTEXTOR [ snippet: Ca2Check, event: active 60x ]
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*CaFullDecrease
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@: ACCUMULATOR [ snippet: CaFullDecrease, rf: active 10x ]
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@: ACCUMULATOR [ snippet: CaFullDecrease, event: active 10x ]
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*Ca2FullIncrease
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@: ACCUMULATOR [ snippet: Ca2FullIncrease, rf: active 10x ]
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@: ACCUMULATOR [ snippet: Ca2FullIncrease, event: active 10x ]
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# *fixed
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@: CONTEXTOR [ snippet: RrpCheck, rf: active 60x ]
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@: CONTEXTOR [ snippet: RrpCheck, event: active 60x ]
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*RrpFullDecrease
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@: ACCUMULATOR [ snippet: RrpFullDecrease, rf: active 10x ]
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@: ACCUMULATOR [ snippet: RrpFullDecrease, event: active 10x ]
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*IncreaseRrpFull
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@: ACCUMULATOR [ snippet: IncreaseRrpFull, rf: active 10x ]
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@: ACCUMULATOR [ snippet: IncreaseRrpFull, event: active 10x ]
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```
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