
include: 
  pre_vgcc.md

PRESYNAPSE

  type: comprehension

    // Intrication
      // Scope
    !DAY: INTRICATE [ scope: &ORGANISM.!DAY ]
    !NIGHT: INTRICATE [ scope: &ORGANISM.!NIGHT ]

      // Context  
    *AP: INTRICATE [ context: &SOMA.*AP ]
    *TunPossible: INTRICATE [ context: &NEURON.*TunPossible ] 

      // Tub
    _NT: INTRICATE [ tub: &ASTROSYNAPSE._NT ] 
    _ATP: INTRICATE [ tub: &ASTROCYTE._ATP ] 
    _eCB: INTRICATE [ tub: &POSTSYNAPSE._eCB ]

    // Instantiation
      // Context
    *VcggIncrease: INSTANTIATE [ context: local ]
    *VcggDecrease: INSTANTIATE [ context: local ]
    *Ca2PrePreActiveDecrease: INSTANTIATE [ context: local ]
    *Ca2PreActiveDecrease: INSTANTIATE [ context: local ]
    *RrpPreActiveDecrease: INSTANTIATE [ context: local ]
    *RrpPreActiveDecrease: INSTANTIATE [ context: local ]

      // Tub
    _Ca2: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _Rrp: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _Rp: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _CaTracesHigh: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _CaTracesMedium: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _CaTracesLow: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]

    _Ca2FullDev: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ]
    _RrpFullDev: INSTANTIATE [ tub: local, full: 60x, act: 30x, empty: 0x ] // serve al DEV

      // Container
    $: INSTANTIATE [ container: MAIN ]
    $: INSTANTIATE [ container: TRACE ]
    $: INSTANTIATE [ container: DECAY ]
    $: INSTANTIATE [ container: RECOVER ]
    $: INSTANTIATE [ container: ADJUST ] // Tuning
    $: INSTANTIATE [ container: DEVELOP ] // !NIGHT

    // Expansion PRE_VGCC, il tub  _@pre_vgcc serve al tuning
    _@pre_vgcc: INSTANTIATE [ tub: EXPAND [ comprehension: PRE_VGCC ], full: 10x, active: 5x, empty: 2x ]

MAIN | !DAY

MAIN

  type: container

  within_scope: !DAY

  // snippet: *AP
    £: INCLUDE [ accumulator: NTreleaseLow, event: act 12x, cost: act 3x ]
    £: INCLUDE [ accumulator: NTreleaseMedium, event: act 9x, cost: act 3x ]
    £: INCLUDE [ accumulator: NTreleaseHigh, event: act 6x, cost: act 3x ]

*AP

NTreleaseLow

NTreleaseLow

    type: accumulator
    in_context: *AP

    hypothesis: _Ca2 mediumness AND _Rrp mediumness AND NOT _ATP empty 
      action: [ _Rrp decrease, _NT increase, _ATP decrease ]
      trace: None

NTreleaseMedium

NTreleaseMedium

    type: accumulator
    in_context: *AP

    hypothesis: ( _Ca2 fullness AND _Rrp mediumness ) OR 
                ( _Ca2 mediumness AND _Rrp fullness ) AND
                NOT _ATP empty 
      action: [ _Rrp decrease, _NT increase, _ATP decrease ]
      trace: None

NTreleaseHigh

NTreleaseHigh
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 fullness AND _Rrp fullness  AND 
                NOT _ATP empty
        action: [ _Rrp decrease, NT increase, _ATP decrease ]
        trace: None

TRACE | !DAY

TRACE

  type: container

  within_scope: !DAY

  // snippet: *AP

    £: INCLUDE [ accumulator: TracesAccLow, event: act 3x, cost: act 3x ]
    £: INCLUDE [ accumulator: TracesAccMedium, event: act 6x, cost: act 3x ]
    £: INCLUDE [ accumulator: TracesAccHigh, event: act 10x, cost: act 3x ]

*AP

Ca2TracesAccuLow
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 emptiness
      action: [ _CaTraceLow increase ]
      trace: None

Ca2TracesAccMedium

Ca2TracesAccMedium
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 mediumness
      action: [ _CaTraceMed increase ]
      trace: None

Ca2TracesAccHigh

Ca2TracesAccumulationHigh
    type: accumulator

    in_context: *AP

    hypothesis: _Ca2 fullness
      action: [ _CaTraceHigh increase ]
      trace: None

DECAY | !DAY

MAIN

  type: container

  within_scope: !DAY

  // snippet: NOT *AP
    £: INCLUDE [ accumulator: eCBClearenceMedium, event: act 24x, cost: act 3x ]
    £: INCLUDE [ accumulator: eCBClearenceLow, event: act 48x, cost: act 3x ]

    £: INCLUDE [ accumulator: TracesClearance, event: act 30x, cost: act 3x ]

NOT *AP

eCBClearance

eCB dipende da POST. Tende a modulare l'entrata di Ca2 degli VGCC.

Qui non facciamo un flush di eCB, riduciamo ogni mezzo secondo (context) di un event di questo episodio.

eCBClearance: ( act: 24x ) # Slow
    type: accumulator

    in_context: NOT *AP

    hypothesis: NOT _eCB empty
      action: [ _eCB decrease ]
      trace: None

Ca2TracesClearance

Qui facciamo un flush di CaTraceX. Deve essere fatto a valle del tuning.

Ca2TracesClearance
    type: accumulator

    in_context: NOT *TunPossible

    hypothesis: NOT _CaTraceHigh empty
      action: [ _CaTRaceHigh decrease ]
      trace: None

    hypothesis: NOT _CaTraceMedium empty
      action: [ _CaTRaceMedium decrease ]
      trace: None

    hypothesis: NOT _CaTraceLow empty
      action: [ _CaTRaceLow decrease ]
      trace: None

RECOVER | !DAY

RECOVER

  type: container

  within_scope: !DAY

  // snippet: NOT *AP
    £: INCLUDE [ accumulator: RPShuttleLow, event: act 24x, cost: act 3x ]
    £: INCLUDE [ accumulator: RPShuttleMedium, event: act 48x, cost: act 3x ]

    £: INCLUDE [ accumulator: RefillGlutamine, event: act 24x, cost: act 3x ]

NOT *AP

RPShuttleLow

This happens in the seconds loop, once per second.

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.

Rate: 0.00 – 0.25

RPShuttleLow
    type: accumulator

    in_context: NOT *AP

    hypothesis: _CaTraceLow fullness OR 
                _RP emptiness OR 
                _Rrp fullness
      action: [ _RP decrease, _Rrp increase ]
      trace: None

RPShuttleMedium

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.

Rate: 0.50 – 0.97

RPShuttleMedium
    type: accumulator

    in_context: *AP

    hypothesis: ( _CaTraceMedium fullness AND _RP mediumness AND _Rrp mediumness ) OR 
                ( _CaTraceHigh fullness AND _RP mediumness AND _Rrp mediumness ) OR   # signal boost
                ( _CaTraceMedium fullness AND _RP fullness AND _Rrp mediumness ) OR   # supply boost
                ( _CaTraceMedium fullness AND _RP mediumness AND _Rrp emptiness )     # vacancy boost
      action: [ _RP decrease, _Rrp increase ]
      trace: None

RPShuttleHigh

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.

Rate: 1.25 – 1.94

RPShuttleHigh
    type: accumulator

    in_context: *AP

    hypothesis: ( _CaTraceHigh fullness AND _RP fullness AND _Rrp mediumness ) OR   # signal + supply
                ( _CaTraceHigh fullness AND _RP mediumness AND _Rrp emptiness ) OR  # signal + vacancy
                ( _CaTraceMedium fullness AND _RP fullness AND _Rrp emptiness )     # supply + vacancy
      action: [ _RP decrease, _Rrp increase ]
      trace: None

RefillRPGlutamine

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.

Step 1 — astrocyte side 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:

refill_RP = Glutamine_pool * conversion_efficiency Glutamine_pool = max(0.0, Glutamine_pool - refill_RP)

Step 2 — presynapse side

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:

The asymmetry that makes depletion possible:

The chain reveals why sustained high-frequency firing eventually depletes the synapse even with all replenishment mechanisms running.

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.

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.

The result is a three-tier buffer with mismatched timescales:

RRP — depletes in seconds, refilled in seconds (fast but shallow) RP — depletes in minutes, refilled in minutes (deep but slow) Gln — depletes over bursts, refilled by glucose (slowest, astrocyte-dependent)

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.

ADJUST | !DAY

ADJUST

  // qui stiamo attivando e disattivando PRE_VGCC. Fra un massimo full e minimo empty (empty puo' non essere 0)

  type: container
  activity_scope: !DAY

  // snippet: *TunPossible
    @: INCLUDE [ contextor: VgccCheck, event: act 60x ]

    // *VcggIncrease
    @: INCLUDE [ accumulator: VcggIncrease, event:act 10x ]

    // *VcggDecrease
    @: INCLUDE [ accumulator: VcggDecrease, event:act 10x ]

*TunPossible

VgccCheck

Qui controlliamo che ci siano le condizioni per aumentare o diminuire l'attivazione di VGCC

VgccCheck

    type contextor
    in_context: *TunPossible

    condition:  _CaTraceHigh fullness
      out_context: *VcggIncrease

    condition:  _CaTraceLow fullness
      out_context: *VcggDecrease

*VcggIncrease

VcggIncrease

VcggIncrease
    type: accumulator

    in_context: *VcggIncrease

    hypothesis:  
      action: 
      trace:

*VcggDecrease

VcggDecrease

VcggDecrease
    type: accumulator

    in_context: *VcggDecrease

    hypothesis:  
      action: 
      trace:

DEVELOP | !NIGHT


DEVELOP
  type: container

  activity_scope: !NIGHT

    // snippet: *fixed
    @: INCLUDE [ contextor: Ca2Check, event: act 60x ]

    // snippet: *CaFullDecrease
    @: INCLUDE [ accumulator: CaFullDecrease, event: act 12x, cost: act 3x ]
    
    // snippet: *Ca2FullIncrease
    @: INCLUDE [ accumulator: Ca2FullIncrease, event: act 12x, cost: act 3x ]

    @: INCLUDE [ contextor: RrpCheck, event: act 60x ]

    // snippet: *RrpFullDecrease
    @: INCLUDE [ accumulator: RrpFullDecrease, event: act 12x, cost: act 3x ]

    // snippet: *IncreaseRrpFull
    @: INCLUDE [ accumulator: IncreaseRrpFull, event: act 12x, cost: act 3x ]

*fixed

Ca2Check

Tens Milliseconds Time Scale

Ca2Check

  type: contextor
  
  in_context: *fixed

    condition: ( empty ) 
      out_context: *CaFullDecrease

    condition: ( full) 
      out_context: *Ca2FullIncrease

*CaFullDecrease

CaFullDecrease

DecreasePreCa2Full

  type: accumulator

  in_context: *CaFullDecrease

    hypothesis: NOT ( full ) AND NOT ( empty ) 
      action: [ increase,  decrease]
      trace: None

*Ca2FullIncrease

Ca2FullIncrease

IncreasePreCa2Full

  type: accumulator
  
  in_context: *Ca2FullIncrease

    hypothesis: NOT ( full ) AND NOT ( empty ) 
      action: [ increase,  decrease]
      trace: None

*fixed

RrpCheck

Tens Milliseconds Time Scale

RrpCheck

  type: contextor
  
  in_context: *fixed

    condition: ( empty ) 
      out_context: *RrpFullDecrease

    condition: ( full) 
      out_context: *IncreaseRrpFull

*RrpFullDecrease

RrpFullDecrease

DecreasePreRrpFull

  type: accumulator

  in_context: *RrpFullDecrease

    hypothesis: NOT ( full ) AND NOT ( empty ) 
      action: [ increase,  decrease]
      trace: None

*RrpFullIncrease

RrpFullIncrease

RrpFullIncrease

  type: accumulator

  in_context: *RrpFullIncrease

    hypothesis: NOT ( full ) AND NOT ( empty ) 
      action: [ increase,  decrease]
      trace: None

13 KiB Raw Blame History Unescape Escape

PRESYNAPSE

MAIN | !DAY

*AP

NTreleaseLow

NTreleaseMedium

NTreleaseHigh

TRACE | !DAY

*AP

Ca2TracesAccMedium

Ca2TracesAccHigh

DECAY | !DAY

NOT *AP

eCBClearance

Ca2TracesClearance

RECOVER | !DAY

NOT *AP

RPShuttleLow

RPShuttleMedium

RPShuttleHigh

RefillRPGlutamine

ADJUST | !DAY

*TunPossible

VgccCheck

*VcggIncrease

VcggIncrease

*VcggDecrease

VcggDecrease

DEVELOP | !NIGHT

*fixed

Ca2Check

*CaFullDecrease

CaFullDecrease

*Ca2FullIncrease

Ca2FullIncrease

*fixed

RrpCheck

*RrpFullDecrease

RrpFullDecrease

*RrpFullIncrease

RrpFullIncrease

13 KiB

Raw Blame History