596 lines
16 KiB
Markdown
596 lines
16 KiB
Markdown
---
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include_toc: true
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---
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// presynapse.md
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**Expansions and modulations**:
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- is expanded and developed by: [AXON](axon.md)
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- is tuned by: [ORGANISM](../../organism.md), organs, modules
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- expands and tunes: [PRE_VGG](pre_vgcc.md)
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- develops _Ca2, _Rrp
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**Introduction**:
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The presynaptic bouton releases neurotransmitter and gathers evidence about whether that release was worth strengthening and worth sustaining. Its behavior unfolds across two DAY contexts and the NIGHT scope.
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During DAY, during AP — the bouton releases neurotransmitter. The amount released depends on:
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- residual calcium from recent spikes (the fast trace), which sets the release drive;
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- the two retrograde messages from the postsynapse — retro_eCB brakes the drive (the postsynapse is over-driven), retro_NO will later confirm that release reached a responsive target;
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- the availability of both fuel and vesicles — release proceeds only if budget covers the cost and the readily-releasable pool is non-empty. These two shortfalls are read differently: a fuel shortfall on a succeeding release is evidence the bouton needs more endurance; an empty pool with fuel to spare is ordinary short-term depression.
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During DAY, during NOT_AP — the bouton consolidates and recovers. With no spike to release, it:
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- receives what arrived — latches the retrograde messages, refills its budget from astrocytic lactate and arrived axonal shipment (contested supply);
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- maintains its traces — accumulates eligibility toward a tag, and stabilizes that tag if dopamine has arrived (the bridge toward strength);
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- recovers its readily-releasable pool from the private reserve, between spikes (which is why high-frequency firing depletes faster than it recovers);
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- lets its traces decay, closing the eligibility, endurance, and tagging windows.
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During NIGHT — the bouton's ceilings are rewritten. Acting on the evidence gathered across the day, NIGHT raises the bouton's structure (active-zone capacity) where a validated tag accumulated, and its budget capacity (mitochondrial endurance) where fuel repeatedly interrupted a succeeding release. Both draw on the same finite material and energy shipped down the axon, so the bouton's two kinds of growth compete — and whatever is not maintained drifts back down.
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# PRESYNAPSE
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```Gen
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include:
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pre_vgcc.md
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PRESYNAPSE
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type: comprehension
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_pre_fast_trace
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_pre_possible_tag _pre_possible_intensity_tag
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_pre_tag _pre_intensity_tag
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_pre_dopamine
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_eCB
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_NO
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_RRP
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_NT
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_pre_budget
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_pre_astro_budget
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_pre_axon_budget
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_pre_endurance_need _pre_endurance_tag
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// Intrication
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// Scope
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!DAY: INTRICATE [ scope: &ORGANISM.!DAY ]
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!NIGHT: INTRICATE [ scope: &ORGANISM.!NIGHT ]
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// Context
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*AP: INTRICATE [ context: &SOMA.*AP ]
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*TunPossible: INTRICATE [ context: &NEURON.*TunPossible ]
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// Tub
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_NT: INTRICATE [ tub: &ASTROSYNAPSE._NT ]
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_ATP: INTRICATE [ tub: &ASTROCYTE._ATP ]
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_eCB: INTRICATE [ tub: &POSTSYNAPSE._eCB ]
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// Instantiation
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// Context
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*VcggIncrease: INSTANTIATE [ context: local ]
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*VcggDecrease: INSTANTIATE [ context: local ]
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*Ca2PrePreActiveDecrease: INSTANTIATE [ context: local ]
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*Ca2PreActiveDecrease: INSTANTIATE [ context: local ]
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*RrpPreActiveDecrease: INSTANTIATE [ context: local ]
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*RrpPreActiveDecrease: INSTANTIATE [ context: local ]
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// Tub
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_Ca2: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_Rrp: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_Rp: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_CaTracesHigh: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_CaTracesMedium: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_CaTracesLow: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_Ca2FullDev: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
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_RrpFullDev: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ] // serve al DEV
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// Container
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void: INSTANTIATE [ container: MAIN ] // !DAY
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void: INSTANTIATE [ container: TRACE ] // !DAY
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void: INSTANTIATE [ container: DECAY ] // !DAY
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void: INSTANTIATE [ container: RECOVER ] // !DAY
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void: INSTANTIATE [ container: ADJUST ] // !DAY Tuning
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void: INSTANTIATE [ container: DEVELOP ] // !NIGHT
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// Expansion
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_@pre_vgcc: INSTANTIATE [ tub: EXPAND [ comprehension: PRE_VGCC ], full: 10x, active: 5x, empty: 2x ] // PRE_VGCC, il tub _@pre_vgcc serve al tuning
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```
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## MAIN
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```Gen
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MAIN
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type: container
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within_scope: !DAY
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// snippet: *AP
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void: INCLUDE [ accumulator: NTreleaseLow, event: act 12x, cost: act 3x ]
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void: INCLUDE [ accumulator: NTreleaseMedium, event: act 9x, cost: act 3x ]
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void: INCLUDE [ accumulator: NTreleaseHigh, event: act 6x, cost: act 3x ]
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```
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#### *AP
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##### NTreleaseLow
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```Gen
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NTreleaseLow
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type: accumulator
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in_context: *AP
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hypothesis: _Ca2 mediumness AND _Rrp mediumness AND NOT _ATP 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
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```Gen
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NTreleaseMedium
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type: accumulator
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in_context: *AP
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hypothesis: ( _Ca2 fullness AND _Rrp mediumness ) OR
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( _Ca2 mediumness AND _Rrp fullness ) AND
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NOT _ATP 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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##### NTreleaseHigh
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```Gen
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NTreleaseHigh
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type: accumulator
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in_context: *AP
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hypothesis: _Ca2 fullness AND _Rrp fullness AND
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NOT _ATP 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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## TRACE | !DAY
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```Gen
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TRACE
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type: container
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within_scope: !DAY
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// snippet: *AP
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void: INCLUDE [ accumulator: TracesAccLow, event: act 3x, cost: act 3x ]
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void: INCLUDE [ accumulator: TracesAccMedium, event: act 6x, cost: act 3x ]
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void: INCLUDE [ accumulator: TracesAccHigh, event: act 10x, cost: act 3x ]
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```
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#### *AP
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```Gen
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Ca2TracesAccuLow
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type: accumulator
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in_context: *AP
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hypothesis: _Ca2 emptiness
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action: [ _CaTraceLow increase ]
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trace: None
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```
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##### Ca2TracesAccMedium
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```Gen
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Ca2TracesAccMedium
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type: accumulator
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in_context: *AP
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hypothesis: _Ca2 mediumness
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action: [ _CaTraceMed increase ]
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trace: None
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```
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##### Ca2TracesAccHigh
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```Gen
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Ca2TracesAccumulationHigh
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type: accumulator
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in_context: *AP
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hypothesis: _Ca2 fullness
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action: [ _CaTraceHigh increase ]
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trace: None
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```
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## DECAY
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```Gen
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MAIN
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type: container
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within_scope: !DAY
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// snippet: NOT *AP
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void: INCLUDE [ accumulator: eCBClearenceMedium, event: act 24x, cost: act 3x ]
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void: INCLUDE [ accumulator: eCBClearenceLow, event: act 48x, cost: act 3x ]
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void: INCLUDE [ accumulator: TracesClearance, event: act 30x, cost: act 3x ]
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```
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#### NOT *AP
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##### eCBClearance
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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 event di questo episodio.
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```Gen
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eCBClearance: ( act: 24x ) # Slow
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type: accumulator
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in_context: NOT *AP
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hypothesis: NOT _eCB empty
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action: [ _eCB decrease ]
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trace: None
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```
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##### Ca2TracesClearance
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Qui facciamo un flush di CaTraceX. Deve essere fatto a valle del tuning.
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```Gen
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Ca2TracesClearance
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type: accumulator
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in_context: NOT *TunPossible
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hypothesis: NOT _CaTraceHigh empty
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action: [ _CaTRaceHigh decrease ]
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trace: None
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hypothesis: NOT _CaTraceMedium empty
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action: [ _CaTRaceMedium decrease ]
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trace: None
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hypothesis: NOT _CaTraceLow empty
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action: [ _CaTRaceLow decrease ]
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trace: None
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```
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## RECOVER
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```Gen
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RECOVER
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type: container
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within_scope: !DAY
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// snippet: NOT *AP
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£: INCLUDE [ accumulator: RPShuttleLow, event: act 24x, cost: act 3x ]
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£: INCLUDE [ accumulator: RPShuttleMedium, event: act 48x, cost: act 3x ]
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£: INCLUDE [ accumulator: RefillGlutamine, event: act 24x, cost: act 3x ]
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```
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#### NOT *AP
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##### RPShuttleLow
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This happens in the seconds loop, once per second.
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The "Hard Bottleneck" State. Recruitment is throttled by a lack of signal, a lack of supply, or a lack of space. If even one of these "Near-Stop" conditions is met, the rate cannot exceed "Slow," regardless of the other two conditions.
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Rate: 0.00 – 0.25
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```Gen
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RPShuttleLow
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type: accumulator
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in_context: NOT *AP
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hypothesis: _CaTraceLow fullness OR
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_RP emptiness OR
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_Rrp fullness
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action: [ _RP decrease, _Rrp increase ]
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trace: None
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```
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##### RPShuttleMedium
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The "Sub-Optimal" State. The machinery is working, but it's held back by partial limitations. This covers cases where the signal is steady but the "piston" isn't firing at full speed, or where a high vacancy in the RRP (emptiness) forces a low signal to work a bit harder.
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Rate: 0.50 – 0.97
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```Gen
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RPShuttleMedium
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type: accumulator
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in_context: *AP
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hypothesis: ( _CaTraceMedium fullness AND _RP mediumness AND _Rrp mediumness ) OR
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( _CaTraceHigh fullness AND _RP mediumness AND _Rrp mediumness ) OR # signal boost
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( _CaTraceMedium fullness AND _RP fullness AND _Rrp mediumness ) OR # supply boost
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( _CaTraceMedium fullness AND _RP mediumness AND _Rrp emptiness ) # vacancy boost
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action: [ _RP decrease, _Rrp increase ]
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trace: None
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```
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##### RPShuttleHigh
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The "High Performance" State. Multiple systems are optimized, but one is still at a "mediumness" level. This represents an active synapse that hasn't reached its absolute peak because either the supply is only 50% or the \_Rrp isn't empty enough to create that "maximal vacuum" pull.
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Rate: 1.25 – 1.94
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```Gen
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RPShuttleHigh
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type: accumulator
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in_context: *AP
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hypothesis: ( _CaTraceHigh fullness AND _RP fullness AND _Rrp mediumness ) OR # signal + supply
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( _CaTraceHigh fullness AND _RP mediumness AND _Rrp emptiness ) OR # signal + vacancy
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( _CaTraceMedium fullness AND _RP fullness AND _Rrp emptiness ) # supply + vacancy
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action: [ _RP decrease, _Rrp increase ]
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trace: None
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```
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##### RefillRPGlutamine
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This happens in the minutes loop, once per minute, via the glutamine shuttle from the astrocyte. It is a two-step process across two cells.
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Step 1 — astrocyte side
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The astrocyte has been accumulating cleared glutamate from the cleft since the last minutes-loop execution. Its glutamine synthetase enzyme converts that glutamate into glutamine, filling the Glutamine_pool. The fraction successfully converted per cycle is conversion_efficiency, which is set by glucose availability and boosted temporarily if the astrocyte calcium wave fired during the preceding seconds:
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refill_RP = Glutamine_pool * conversion_efficiency
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Glutamine_pool = max(0.0, Glutamine_pool - refill_RP)
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Step 2 — presynapse side
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The glutamine crosses into the presynapse, where glutaminase converts it back into glutamate. That glutamate is immediately repackaged into vesicles and added to N_RP:
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**The asymmetry that makes depletion possible**:
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The chain reveals why sustained high-frequency firing eventually depletes the synapse even with all replenishment mechanisms running.
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The RRP holds at most `Max_RRP = 20` vesicles. At 20 Hz with strong Ca2, release can draw 2-4 vesicles per spike — potentially exhausting the RRP in under a second. The seconds loop can move vesicles from RP to RRP at a maximum rate of `k_rec_fast = 5 /s`, meaning at most 5 vesicles per second under ideal conditions. Release outpaces recruitment by roughly an order of magnitude during a burst.
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The RP holds up to `Max_RP = 200` vesicles — ten times the RRP. At sustained 20 Hz the RP can sustain firing for tens of seconds even after the RRP is repeatedly emptied, as long as recruitment keeps pace. But the minutes loop only refills N_RP once per minute at a rate limited by `Glutamine_pool * conversion_efficiency`. If glucose is low or the astrocyte wave has not fired, this replenishment may add only a fraction of what was consumed.
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The result is a three-tier buffer with mismatched timescales:
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RRP — depletes in seconds, refilled in seconds (fast but shallow)
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RP — depletes in minutes, refilled in minutes (deep but slow)
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Gln — depletes over bursts, refilled by glucose (slowest, astrocyte-dependent)
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Each tier buys time for the one below it to respond. When all three are depleted simultaneously — which only happens under prolonged high-frequency firing with insufficient glucose — the synapse has no remaining buffer and goes silent until the minutes loop restores the Glutamine_pool.
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## ADJUST
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```Gen
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ADJUST
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// qui stiamo attivando e disattivando PRE_VGCC. Fra un massimo full e minimo empty (empty puo' non essere 0)
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type: container
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activity_scope: !DAY
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// snippet: *TunPossible
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@: INCLUDE [ contextor: VgccCheck, event: act 60x ]
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// *VcggIncrease
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@: INCLUDE [ accumulator: VcggIncrease, event:act 10x ]
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// *VcggDecrease
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@: INCLUDE [ accumulator: VcggDecrease, event:act 10x ]
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```
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#### *TunPossible
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##### VgccCheck
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Qui controlliamo che ci siano le condizioni per aumentare o diminuire l'attivazione di VGCC
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```Gen
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VgccCheck
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type contextor
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in_context: *TunPossible
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condition: _CaTraceHigh fullness
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out_context: *VcggIncrease
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condition: _CaTraceLow fullness
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out_context: *VcggDecrease
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```
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#### *VcggIncrease
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##### VcggIncrease
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```Gen
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VcggIncrease
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type: accumulator
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in_context: *VcggIncrease
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hypothesis:
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action:
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trace:
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```
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#### *VcggDecrease
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##### VcggDecrease
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```Gen
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VcggDecrease
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type: accumulator
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in_context: *VcggDecrease
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hypothesis:
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action:
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trace:
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```
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## DEVELOP
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```Gen
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DEVELOP
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type: container
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activity_scope: !NIGHT
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// snippet: *fixed
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@: INCLUDE [ contextor: Ca2Check, event: act 60x ]
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// snippet: *CaFullDecrease
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@: INCLUDE [ accumulator: CaFullDecrease, event: act 12x, cost: act 3x ]
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// snippet: *Ca2FullIncrease
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@: INCLUDE [ accumulator: Ca2FullIncrease, event: act 12x, cost: act 3x ]
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@: INCLUDE [ contextor: RrpCheck, event: act 60x ]
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// snippet: *RrpFullDecrease
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@: INCLUDE [ accumulator: RrpFullDecrease, event: act 12x, cost: act 3x ]
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// snippet: *IncreaseRrpFull
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@: INCLUDE [ accumulator: IncreaseRrpFull, event: act 12x, cost: act 3x ]
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```
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#### *fixed
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##### Ca2Check
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***Tens Milliseconds Time Scale***
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```Gen
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Ca2Check
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type: contextor
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in_context: *fixed
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condition: ( empty )
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out_context: *CaFullDecrease
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condition: ( full)
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out_context: *Ca2FullIncrease
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```
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##### *CaFullDecrease
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###### CaFullDecrease
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```Gen
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DecreasePreCa2Full
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type: accumulator
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in_context: *CaFullDecrease
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hypothesis: NOT ( full ) AND NOT ( empty )
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action: [ increase, decrease]
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trace: None
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```
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##### *Ca2FullIncrease
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###### Ca2FullIncrease
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```Gen
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IncreasePreCa2Full
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type: accumulator
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in_context: *Ca2FullIncrease
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hypothesis: NOT ( full ) AND NOT ( empty )
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action: [ increase, decrease]
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trace: None
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```
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#### *fixed
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##### RrpCheck
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***Tens Milliseconds Time Scale***
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```Gen
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RrpCheck
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type: contextor
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in_context: *fixed
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condition: ( empty )
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out_context: *RrpFullDecrease
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||
condition: ( full)
|
||
out_context: *IncreaseRrpFull
|
||
```
|
||
|
||
##### *RrpFullDecrease
|
||
|
||
###### RrpFullDecrease
|
||
|
||
```Gen
|
||
DecreasePreRrpFull
|
||
|
||
type: accumulator
|
||
|
||
in_context: *RrpFullDecrease
|
||
|
||
hypothesis: NOT ( full ) AND NOT ( empty )
|
||
action: [ increase, decrease]
|
||
trace: None
|
||
```
|
||
|
||
##### *RrpFullIncrease
|
||
|
||
###### RrpFullIncrease
|
||
|
||
```Gen
|
||
RrpFullIncrease
|
||
|
||
type: accumulator
|
||
|
||
in_context: *RrpFullIncrease
|
||
|
||
hypothesis: NOT ( full ) AND NOT ( empty )
|
||
action: [ increase, decrease]
|
||
trace: None
|
||
```
|