CaTraces, CaClearance, eCB clearance
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@@ -43,8 +43,6 @@ The presynapse does not release blindly. Its behaviour is governed by three inte
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---
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**The loops**:
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**The NT loop** is the supply chain of the synapse, operating across all three timescales.
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- On the millisecond scale, action potentials trigger Ca²⁺-driven release of NT from the RRP into the cleft. NT in the cleft feeds back on itself within the same millisecond — high cleft concentration suppresses further release, acting as a local brake.
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@@ -200,14 +198,18 @@ container: BEH-PRE
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```
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### ms: behavior
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### ms: behaviors
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#### RRPConcentration: Context
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#### AP-RRPConcentration: Context
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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 deve essere MOLTO piu' basso della durata di un 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.
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Questo poi per permettere la diversa contestualizzazione degli episodi di NTrelease, a piu' o meno alta velocita'.
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```Gen
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context: RRPConcentration
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context: AP-RRPConcentration
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contained_by: BEH-PRE
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in_context: AP
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@@ -220,10 +222,12 @@ context: RRPConcentration
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out_context: RRPFull
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```
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#### Ca2+Concentration: Context
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#### AP-Ca2+Concentration: Context
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Qui controlliamo la concentrazione nel contesto di un AP.
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```Gen
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context: Ca2+Concentration
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context: AP-Ca2+Concentration
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contained_by: BEH-PRE
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in_context: AP
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@@ -236,7 +240,7 @@ context: Ca2+Concentration
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out_context: Ca2+Full
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```
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#### NTrelease: Episodes
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#### NTrelease
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Ci sono 4 casi che dipendono da RRP, Ca2+ e NT. 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 al crescere di NT. 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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@@ -244,6 +248,8 @@ Ci sono 4 casi che dipendono da RRP, Ca2+ e NT. L'idea e' che la quantita' di RR
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##### NTreleaseMaximum: Episode
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NT empty
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```Gen
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episode: NTreleaseMaximum
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contained_by: BEH-PRE
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@@ -258,6 +264,8 @@ episode: NTreleaseMaximum
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##### NTreleaseHigh: Episode
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Solo in questo caso NT modera! NT NOT empty
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```Gen
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episode: NTreleaseHigh
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contained_by: BEH-PRE
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@@ -265,13 +273,15 @@ episode: NTreleaseHigh
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in_context: (Ca2+Full AND RRPFull)
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rf: ( active: 6x ) # High
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hypothesis: NOT (NT empty) # solo in questo caso NT modera!
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hypothesis: NOT (NT empty)
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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##### NTreleaseMedium: Episode
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In tutti i casi di NT
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```Gen
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episode: NTreleaseMedium
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contained_by: BEH-PRE
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@@ -279,13 +289,15 @@ episode: NTreleaseMedium
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in_context: (Ca2+Full AND RRPMedium) OR (Ca2+Medium AND RRPFull)
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rf: ( active: 9x ) # Medium
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hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
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hypothesis: (NT empty) OR NOT (NT empty)
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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##### NTreleaseLow: Episode
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In tutti i casi di NT
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```Gen
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episode: NTreleaseLow
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contained_by: BEH-PRE
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@@ -293,7 +305,7 @@ episode: NTreleaseLow
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in_context: (Ca2+Medium AND RRPMedium)
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rf: ( active: 12x ) # Low
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hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
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hypothesis: (NT empty) OR NOT (NT empty)
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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@@ -308,19 +320,55 @@ Qui eliminiamo Ca2+. Non comprendiamo per ora:
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Quindi non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA.
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### sec: behavior
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Abbiamo il caso di clearance nel contesto di un AP e non nel contesto di AP, per eliminare il Ca2+ fra le spike.
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...
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##### AP-CaClearanceHigh: Episode
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#### eCB concentration
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```Gen
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episode: AP-CaClearanceHigh
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contained_by: BEH-PRE
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Limita rilascio NT: Dipende da POST che tende a bloccare rialascio di NT se non servono
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in_context: Ca2+Full
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rf: ( active: 3x ) # High
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#### CaTrace concentration
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hypothesis: NOT (Ca2+ empty)
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action: [Ca2+ decrease]
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trace: None
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```
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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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##### AP-CaClearanceMedium: Episode
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Serve a dare la velocita' al trasporto di vesicles da RP a RRP. Ha un decadimento proprio il che dice alla Presinapsi di accellerare se da poco c'e' stata una spike, altrimenti di andare piu' piano. So after one second of silence Tr_Ca 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.
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```Gen
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episode: AP-CaClearanceMedium
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contained_by: BEH-PRE
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in_context: Ca2+Medium
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rf: ( active: 6x ) # Medium
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hypothesis: NOT (Ca2+ empty)
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action: [Ca2+ decrease]
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trace: None
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```
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##### NotAP-CaClearance: Episode
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```Gen
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episode: NotAP-CaClearance
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contained_by: BEH-PRE
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in_context: NOT AP
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rf: ( active: 24x ) # Low
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hypothesis: NOT (Ca2+ empty)
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action: [Ca2+ decrease]
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trace: None
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```
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#### CaTraces accumulation
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Serve a dare la velocita' al trasporto di vesicles da RP a RRP. 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 Tr_Ca 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.
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spike → Ca_micro rises → Tr_Ca rises slowly
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→ Tr_Ca stays elevated for ~1-2 s after burst
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@@ -328,11 +376,17 @@ spike → Ca_micro rises → Tr_Ca rises slowly
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→ RRP refills faster
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→ more vesicles available for the next burst
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Tr_Ca = Tr_Ca + (Ca_micro - Tr_Ca / tau_Tr_Ca) * dt
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This is a leaky integrator — it has two competing forces at every step. The Ca_micro term pushes Tr_Ca upward toward the current calcium level. The - Tr_Ca / tau_Tr_Ca term pulls it back down toward zero at a rate proportional to how high it already is. The balance between these two forces means Tr_Ca is always chasing Ca_micro but never quite reaching it, and always decaying when Ca_micro is low.
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During a spike, Ca_micro jumps sharply. Tr_Ca rises but more slowly — it integrates rather than jumps. Between spikes, Ca_micro falls back toward zero as the pumps clear it. Tr_Ca also falls, but much more slowly because tau_Tr_Ca = 1000 ms — it remembers the spike for roughly a second after it happened. Over a burst of many spikes, Tr_Ca climbs steadily as each spike adds to the residual trace before the previous one has fully decayed. A long silence after a burst allows Tr_Ca to decay exponentially back toward zero.
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The result is that Tr_Ca 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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### sec: behaviors
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#### eCB clearance
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Qui forse devo fare il flush e anche di CaTrace. Limita rilascio NT: Dipende da POST che tende a bloccare rialascio di NT se non servono
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#### CaTraces clearance
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#### RP->RRP shuttling
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How RP is moved to RRP
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@@ -351,7 +405,7 @@ N_RP — how many vesicles are available in the reserve. As N_RP depletes, fewer
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(Max_RRP - N_RRP) / Max_RRP — the headroom in the RRP, normalised. When the RRP is nearly full, recruitment slows automatically because there is little room to fill. When the RRP is empty after a burst, headroom is maximal and recruitment runs at full speed. This prevents overfilling and makes the system self-regulating — recruitment is fastest precisely when it is most needed.
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The two guard clauses ensure the arithmetic stays physical: refill_amount cannot be negative, and cannot exceed what N_RP actually contains.
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### min: behavior
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### min: behaviors
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#### Refill RP from Glutamine
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@@ -421,7 +475,7 @@ container: BEH-PRE-VGCC
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### ms: behavior VGCC
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#### Ca2+enter: Episodes
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#### Ca2+enter
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Here we comprehend the breaking activity on VGCC by: CDI,eCB and mGluR:
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@@ -441,10 +495,10 @@ Qui sostituiamo:
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Devo controllare che le condizioni sotto siano esaustive.
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##### Open: Episode
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##### Ca2+enterOpen: Episode
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```Gen
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episode: Open
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episode: Ca2+enterOpen
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contained_by: BEH-PRE-VGCC
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in_context: AP
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@@ -455,10 +509,10 @@ episode: Open
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trace: None
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```
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##### Reduced-partial: Episode
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##### Ca2+enterReduced-partial: Episode
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```Gen
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episode: Reduced-partial
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episode: Ca2+enterReduced-partial
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contained_by: BEH-PRE-VGCC
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in_context: AP
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@@ -469,10 +523,10 @@ episode: Reduced-partial
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trace: None
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```
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##### Suppressed: Episode
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##### Ca2+enterSuppressed: Episode
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```Gen
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episode: Supressed
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episode: Ca2+enterSupressed
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contained_by: BEH-PRE-VGCC
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in_context: AP
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