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elements/neuron/presynapse.md
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@@ -13,7 +13,6 @@ Qui comprendiamo:
```Gen ```Gen
PRESYNAPSE PRESYNAPSE
type: comprehension type: comprehension
expansion: expansion:
@@ -24,29 +23,33 @@ PRESYNAPSE
intrication: intrication:
# Scope # Scope
!DAY: SCOPE [ ref: &ORGANISM.!DAY] !DAY: INTRICATION [ ref: &ORGANISM.!DAY ]
!NIGHT: SCOPE [ ref: &ORGANISM.!NIGHT] !NIGHT: INTRICATION [ ref: &ORGANISM.!NIGHT ]
# Context # Context
*AP: CONTEXT [&SOMA.*AP] *AP: INTRICATION [ ref: &SOMA.*AP ]
*TunePossible: INTRICATION [ ref: &... ] # To be defined...
# Tub # Tub
_NT: TUB [ ref: &ASTROSYNAPSE._NT] _NT: INTRICATION [ ref: &ASTROSYNAPSE._NT ]
_ATP: TUB [ ref: &ASTROCYTE._ATP] _ATP: INTRICATION [ ref: &ASTROCYTE._ATP ]
_eCB: TUB [ ref: &POSTSYNAPSE._eCB] _eCB: INTRICATION [ ref: &POSTSYNAPSE._eCB ]
instantiation: instantiation:
# Context # Context
*TunePossible: CONTEXT [ref: &...] *TryTunUpPreVcgg: CONTEXT []
*TryTunDownPreVcgg: CONTEXT []
# Tub # Tub
_Ca2+: TUB [ full: 60x, active: 30x, empty: 0x ] _Ca2: TUB [ full: 60x, active: 30x, empty: 0x ]
_Rrp: TUB [ full: 30x, active: 15x, empty: 0x ] _Rrp: TUB [ full: 30x, active: 15x, empty: 0x ]
_Rp: TUB [ full: 30x, active: 15x, empty: 0x ] _Rp: TUB [ full: 30x, active: 15x, empty: 0x ]
_CaTraces: TUB [ full: 50x, active: 0x, empty: 0x ] _CaTracesHigh: TUB [ full: 50x, active: 0x, empty: 0x ]
_CaTracesMedium: TUB [ full: 50x, active: 0x, empty: 0x ]
_CaTracesLow: TUB [ full: 50x, active: 0x, empty: 0x ]
_Ca2+FullDev: TUB [ full: 100x, active: _Ca2+.full, empty: 40x ] _Ca2FullDev: TUB [ full: 100x, active: _Ca2.full, empty: 40x ]
# serve al dev # serve al dev
# Behaviour # Behaviour
@@ -66,33 +69,33 @@ MAIN_PRE
snippet: snippet:
# *AP # *AP
@: ACCUMULATOR [snippet: NTreleaseLow, RF: active 12x] @: ACCUMULATOR [ snippet: NTreleaseLow, rf: active 12x ]
@: ACCUMULATOR [snippet: NTreleaseMedium, RF: active 9x] @: ACCUMULATOR [ snippet: NTreleaseMedium, rf: active 9x ]
@: ACCUMULATOR [snippet: NTreleaseHigh, RF: active 6x] @: ACCUMULATOR [ snippet: NTreleaseHigh, rf: active 6x ]
@: ACCUMULATOR [snippet: TracesAccLow, RF: active 3x] @: ACCUMULATOR [ snippet: TracesAccLow, rf: active 3x ]
@: ACCUMULATOR [snippet: TracesAccMedium, RF: active 6x] @: ACCUMULATOR [ snippet: TracesAccMedium, rf: active 6x ]
@: ACCUMULATOR [snippet: TracesAccHigh, RF: active 10x] @: ACCUMULATOR [ snippet: TracesAccHigh, rf: active 10x ]
# NOT *AP # NOT *AP
@: ACCUMULATOR [snippet: eCBClearenceMedium, RF: active 24x] @: ACCUMULATOR [ snippet: eCBClearenceMedium, rf: active 24x ]
@: ACCUMULATOR [snippet: eCBClearenceLow, RF: active 48x] @: ACCUMULATOR [ snippet: eCBClearenceLow, rf: active 48x ]
@: ACCUMULATOR [snippet: RPShuttleLow, RF: active 24x] @: ACCUMULATOR [ snippet: RPShuttleLow, rf: active 24x ]
@: ACCUMULATOR [snippet: RPShuttleMedium, RF: active 48x] @: ACCUMULATOR [ snippet: RPShuttleMedium, rf: active 48x ]
@: ACCUMULATOR [snippet: RefillGlutamine, RF: active 24x] @: ACCUMULATOR [ snippet: RefillGlutamine, rf: active 24x ]
@: ACCUMULATOR [snippet: TracesClearance, RF: active 30x] @: ACCUMULATOR [ snippet: TracesClearance, rf: active 30x ]
``` ```
**Tubs:** **Tubs:**
- **_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 - **_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
- **_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. - **_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.
- **_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. - **_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.
- **_NT**: Neuro Transmitter, released in the synapse by the vescicles. The release increses NT and decreases RRP - **_NT**: Neuro Transmitter, released in the synapse by the vescicles. The release increses NT and decreases RRP
- **_CaTraces**: sono le tracce di permanenza della concentrazione di Ca2+. Servono alla modulazione (TUN) - **_CaTracesXXX**: sono le tracce di permanenza della concentrazione di Ca2. Servono alla modulazione (TUN)
- **_eCB**: retrograde signal updates from postsynapsis (postsynaptic input) - **_eCB**: retrograde signal updates from postsynapsis (postsynaptic input)
#### *AP #### *AP
@@ -105,11 +108,11 @@ RF di interacting deve essere MOLTO piu' basso di un RF di AP. In maniera da ess
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. 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.
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. 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.
--- ---
NT empty. Qui siamo contestualizzati se Ca2+ full, il che dovrebbe significare indirettamente che non ci sono NT nella SYN. NT empty. Qui siamo contestualizzati se Ca2 full, il che dovrebbe significare indirettamente che non ci sono NT nella SYN.
In tutti i casi di NT In tutti i casi di NT
@@ -117,11 +120,12 @@ In tutti i casi di NT
```Gen ```Gen
NTreleaseLow NTreleaseLow
type: accumulator
in_context: *AP in_context: *AP
hypothesis: ( _Ca2+ mediumness ) AND ( _Rrp mediumness ) AND NOT( _ATP empty ) hypothesis: _Ca2 mediumness AND _Rrp mediumness AND NOT _ATP empty
action: [_Rrp decrease, _Nt increase, _ATP decrease] action: [ _Rrp decrease, _NT increase, _ATP decrease ]
trace: None trace: None
``` ```
@@ -129,13 +133,14 @@ NTreleaseLow
```Gen ```Gen
NTreleaseMedium NTreleaseMedium
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (( _Ca2+ fullness ) AND ( _Rrp mediumness ) OR hypothesis: ( _Ca2 fullness AND _Rrp mediumness ) OR
( _Ca2+ mediumness ) AND ( _Rrp fullness )) AND ( _Ca2 mediumness AND _Rrp fullness ) AND
NOT( _ATP empty ) NOT _ATP empty
action: [_Rrp decrease, Nt increase, _ATP decrease] action: [ _Rrp decrease, _NT increase, _ATP decrease ]
trace: None trace: None
``` ```
@@ -143,16 +148,17 @@ NTreleaseMedium
```Gen ```Gen
NTreleaseHigh NTreleaseHigh
type: accumulator
in_context: *AP in_context: *AP
hypothesis: ( _Ca2+ fullness ) AND ( _Rrp fullness ) AND hypothesis: _Ca2 fullness AND _Rrp fullness AND
NOT( _ATP empty ) NOT _ATP empty
action: [_Rrp decrease, NT increase, _ATP decrease] action: [ _Rrp decrease, NT increase, _ATP decrease ]
trace: None trace: None
``` ```
##### Ca2+TracesAccLow ##### Ca2TracesAccLow
Serve a: Serve a:
@@ -162,39 +168,42 @@ Serve a:
- Abbiamo 3 tracce, high, medium and low. Andiamo a verificare una combinazione di queste per fare la modulazione - Abbiamo 3 tracce, high, medium and low. Andiamo a verificare una combinazione di queste per fare la modulazione
- 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. - 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.
- 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. - 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.
- 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. - 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.
```Gen ```Gen
Ca2+TracesAccuLow Ca2TracesAccuLow
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ emptiness) hypothesis: _Ca2 emptiness
action: [CaTraceLow increase] action: [ _CaTraceLow increase ]
trace: None trace: None
``` ```
##### Ca2+TracesAccMedium ##### Ca2TracesAccMedium
```Gen ```Gen
Ca2+TracesAccMedium Ca2TracesAccMedium
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ mediumness) hypothesis: _Ca2 mediumness
action: [CaTraceMed increase] action: [ _CaTraceMed increase ]
trace: None trace: None
``` ```
##### Ca2+TracesAccHigh ##### Ca2TracesAccHigh
```Gen ```Gen
Ca2+TracesAccumulationHigh Ca2TracesAccumulationHigh
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ fullness) hypothesis: _Ca2 fullness
action: [CaTraceHigh increase] action: [ _CaTraceHigh increase ]
trace: None trace: None
``` ```
@@ -202,17 +211,18 @@ Ca2+TracesAccumulationHigh
##### eCBClearance ##### eCBClearance
eCB dipende da POST. Tende a modulare l'entrata di Ca2+ degli VGCC. 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 RF di questo episodio. Qui non facciamo un flush di eCB, riduciamo ogni mezzo secondo (context) di un RF di questo episodio.
```Gen ```Gen
eCBClearance: ( active: 24x ) # Slow eCBClearance: ( active: 24x ) # Slow
type: accumulator
in_context: NOT *AP in_context: NOT *AP
hypothesis: NOT (eCB empty) hypothesis: NOT _eCB empty
action: [eCB decrease] action: [ _eCB decrease ]
trace: None trace: None
``` ```
@@ -226,13 +236,14 @@ Rate: 0.00 – 0.25
```Gen ```Gen
RPShuttleLow RPShuttleLow
type: accumulator
in_context: NOT *AP in_context: NOT *AP
hypothesis: (CaTraceLow fullness) OR hypothesis: _CaTraceLow fullness OR
(RP emptiness) OR _RP emptiness OR
(_Rrp fullness) _Rrp fullness
action: [RP decrease, _Rrp increase] action: [ _RP decrease, _Rrp increase ]
trace: None trace: None
``` ```
@@ -244,14 +255,15 @@ Rate: 0.50 – 0.97
```Gen ```Gen
RPShuttleMedium RPShuttleMedium
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (CaTraceMedium fullness) AND (RP mediumness) AND (_Rrp mediumness) OR hypothesis: ( _CaTraceMedium fullness AND _RP mediumness AND _Rrp mediumness ) OR
(CaTraceHigh fullness) AND (RP mediumness) AND (_Rrp mediumness) OR # signal boost ( _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 fullness AND _Rrp mediumness ) OR # supply boost
(CaTraceMedium fullness) AND (RP mediumness) AND (_Rrp emptiness) # vacancy boost ( _CaTraceMedium fullness AND _RP mediumness AND _Rrp emptiness ) # vacancy boost
action: [RP decrease, _Rrp increase] action: [ _RP decrease, _Rrp increase ]
trace: None trace: None
``` ```
@@ -263,13 +275,14 @@ Rate: 1.25 – 1.94
```Gen ```Gen
RPShuttleHigh RPShuttleHigh
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (CaTraceHigh fullness) AND (RP fullness) AND (_Rrp mediumness) OR # signal + supply hypothesis: ( _CaTraceHigh fullness AND _RP fullness AND _Rrp mediumness ) OR # signal + supply
(CaTraceHigh fullness) AND (RP mediumness) AND (_Rrp emptiness) OR # signal + vacancy ( _CaTraceHigh fullness AND _RP mediumness AND _Rrp emptiness ) OR # signal + vacancy
(CaTraceMedium fullness) AND (RP fullness) AND (_Rrp emptiness) # supply + vacancy ( _CaTraceMedium fullness AND _RP fullness AND _Rrp emptiness ) # supply + vacancy
action: [RP decrease, _Rrp increase] action: [ _RP decrease, _Rrp increase ]
trace: None trace: None
``` ```
@@ -291,7 +304,7 @@ The glutamine crosses into the presynapse, where glutaminase converts it back in
The chain reveals why sustained high-frequency firing eventually depletes the synapse even with all replenishment mechanisms running. 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 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 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.
@@ -303,25 +316,26 @@ Gln — depletes over bursts, refilled by glucose (slowest, astrocyte-depend
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. 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.
##### Ca2+TracesClearance ##### Ca2TracesClearance
Qui facciamo un flush di CaTraceX. Deve essere fatto a valle del tuning. Qui facciamo un flush di CaTraceX. Deve essere fatto a valle del tuning.
```Gen ```Gen
Ca2+TracesClearance Ca2TracesClearance
type: accumulator
in_context: NOT *TunePossible in_context: NOT *TunePossible
hypothesis: NOT (CaTraceHigh empty) hypothesis: NOT _CaTraceHigh empty
action: [CaTRaceHigh decrease] action: [ _CaTRaceHigh decrease ]
trace: None trace: None
hypothesis: NOT (CaTraceMedium empty) hypothesis: NOT _CaTraceMedium empty
action: [CaTRaceMedium decrease] action: [ _CaTRaceMedium decrease ]
trace: None trace: None
hypothesis: NOT (CaTraceLow empty) hypothesis: NOT _CaTraceLow empty
action: [CaTRaceLow decrease] action: [ _CaTRaceLow decrease ]
trace: None trace: None
``` ```
@@ -330,32 +344,22 @@ Ca2+TracesClearance
```Gen ```Gen
TUNE_VGCC_PRE TUNE_VGCC_PRE
# qui stiamo aggiungendo o eliminando {VGCC_PRE}. Fra un massimo full e minimo empty (empty puo' non essere 0) type: behaviour
# qui stiamo aggiungendo o eliminando VGCC_PRE. Fra un massimo full e minimo empty (empty puo' non essere 0)
# contained_by: PRESYNAPSE non e' contenuto, si attacca. # contained_by: PRESYNAPSE non e' contenuto, si attacca.
activity_scope: !DAY activity_scope: !DAY
type: behaviour
context_intricated:
- *TunePossible ( contained_by: DAY-N )
tub_passed:
_VgccPre: TUB [pass.@VGCC_PRE]
tub_local:
tub_intricated:
snippet: snippet:
# *TunePossible # *TunePossible
CheckVgccPreTun: CONTEXTOR [RF: active 60x] @: CONTEXTOR [ snippet: CheckVgccPreTun, rf: active 60x ]
*TryTunUpPreVcgg # *TryTunUpPreVcgg
PossibleUpPreVgccTun: ACCUMULATOR [RF:active 10x] @: ACCUMULATOR [ snippet: PossibleUpPreVgccTun, rf:active 10x ]
*TryTunDownPreVcgg # *TryTunDownPreVcgg
PossibleDownPreVgccTun: ACCUMULATOR [RF:active 10x] @: ACCUMULATOR [ snippet: PossibleDownPreVgccTun, rf:active 10x ]
``` ```
#### *TunePossible #### *TunePossible
@@ -366,34 +370,41 @@ Qui controlliamo che ci siano le condizioni per aumentare o diminuire la quantit
```Gen ```Gen
CheckVgccPreTun CheckVgccPreTun
type contextor
in_context: *TunePossible in_context: *TunePossible
condition: ( CaTraceHigh fullness ) condition: _CaTraceHigh fullness
out_context: *TryTunUpPreVcgg out_context: *TryTunUpPreVcgg
condition: ( CaTraceLow fullness ) condition: _CaTraceLow fullness
out_context: *TryTunDownPreVcgg out_context: *TryTunDownPreVcgg
``` ```
#### *TryTunUpPreVcgg
##### PossibleUpPreVgccTun ##### PossibleUpPreVgccTun
```Gen ```Gen
PossibleUpPreVgccTun PossibleUpPreVgccTun
type: accumulator
in_context: TryTunUpPreVcgg_ctx in_context: *TryTunUpPreVcgg
hypothesis: hypothesis:
action: action:
trace: trace:
``` ```
#### *TryTunDownPreVcgg
##### PossibleDownPreVgccTun: ( active: 10x ) accumulator ##### PossibleDownPreVgccTun: ( active: 10x ) accumulator
```Gen ```Gen
PossibleDownPreVgccTun PossibleDownPreVgccTun
type: accumulator
in_context: TryTunDownPreVcgg_ctx in_context: *TryTunDownPreVcgg
hypothesis: hypothesis:
action: action:
@@ -406,10 +417,21 @@ Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della d
```Gen ```Gen
VGCC-PRE VGCC-PRE
type: comprehension type: comprehension
instantiate_behaviour: # Scope
BEHAVIOR_VGCC_PRE: behaviour [] !DAY: INTRICATION [ ref: &ORGANISM.!DAY ]
!NIGHT: INTRICATION [ ref: &ORGANISM.!NIGHT ]
# Context
*AP: INTRICATION [ ref: &SOMA.*AP ]
# Tub
_NT: INTRICATION [ ref: &ASTROSYNAPSE._NT ]
_Ca2: INTRICATION [ ref: &PRESYNAPSE._Ca2 ]
# Behaviour
@: BEHAVIOUR [ behaviour: VGCC_PRE_BEH ]
``` ```
### BEHAVIOR_VGCC_PRE ### BEHAVIOR_VGCC_PRE
@@ -417,26 +439,20 @@ instantiate_behaviour:
Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare. Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.
```Gen ```Gen
BEHAVIOR_VGCC_PRE VGCC_PRE_BEH
activity_scope: !DAY
type: behaviour type: behaviour
tub_intricated: within_scope: !DAY
- _Ca2+ ( contained_by: PRESYNAPSE-BHE )
- NT ( contained_by: SYN )
context_intricated:
- AP ( contained_by: SOMA )
snippets: snippets:
# *AP
@: ACCUMULATOR [ snippet: Ca2enterLow, rf: active 12x ]
@: ACCUMULATOR [ snippet: Ca2enterMedium, rf: active 6x ]
@: ACCUMULATOR [ snippet: Ca2enterHigh, rf: active 3x ]
Ca2+enterLow: ACCUMULATOR [RF: active 12x] # NOT *AP
Ca2+enterMedium: ACCUMULATOR [RF: active 6x] @: ACCUMULATOR [ snippet: Ca2ClearanceLow, rf: active 24x ]
Ca2+enterHigh: ACCUMULATOR [RF: active 3x] @: ACCUMULATOR [ snippet: Ca2ClearanceHigh, rf: active 4x ]
Ca2+ClearanceLow: ACCUMULATOR [RF: active 24x]
Ca2+ClearanceHigh: ACCUMULATOR [RF: active 4x]
``` ```
@@ -450,60 +466,63 @@ Here we comprehend the breaking activity on VGCC by: CDI, eCB and mGluR:
Qui semplifichiamo: Qui semplifichiamo:
- Approssimiamo CDI con concentrazione di Ca2+. - Approssimiamo CDI con concentrazione di Ca2.
-- CDI is calcium-dependent inactivation of VGCCs. The inactivation happens because Ca²⁺ enters through the channel and binds to a calmodulin tethered to the channel's intracellular face, physically blocking it from reopening. This is a local, channel-specific event — it requires Ca²⁺ to be flowing through that channel right now, not residual Ca²⁺ drifting in the cytosol between spikes. -- CDI is calcium-dependent inactivation of VGCCs. The inactivation happens because Ca2 enters through the channel and binds to a calmodulin tethered to the channel's intracellular face, physically blocking it from reopening. This is a local, channel-specific event — it requires Ca2 to be flowing through that channel right now, not residual Ca2 drifting in the cytosol between spikes.
-- The recovery, by contrast, should run every millisecond unconditionally — CDI de-inactivation is a continuous process that proceeds whenever Ca²⁺ dissociates from calmodulin, which depends on the ambient Ca_micro level at all times. -- The recovery, by contrast, should run every millisecond unconditionally — CDI de-inactivation is a continuous process that proceeds whenever Ca2 dissociates from calmodulin, which depends on the ambient Ca_micro level at all times.
- Approssimiamo mGluR con concentrazione NT - Approssimiamo mGluR con concentrazione NT
- **Open** — zero active brakes. mGluR alone never escapes this group because its ceiling is alpha_mGluR = 0.4, meaning even at full it only removes 40% of conductance, leaving 60% — still above the 85% threshold. So mGluR is irrelevant to the open/not-open boundary. Only CDI and eCB decide. - **Open** — zero active brakes. mGluR alone never escapes this group because its ceiling is alpha_mGluR = 0.4, meaning even at full it only removes 40% of conductance, leaving 60% — still above the 85% threshold. So mGluR is irrelevant to the open/not-open boundary. Only CDI and eCB decide.
- **Reduced/partial** — exactly one meaningful brake active. Either CDI has started building (mediumness), or eCB has risen from sustained postsynaptic activity, but not both simultaneously. The system is aware something is happening but has not compounded yet. This is the normal operating range during moderate sustained firing. - **Reduced/partial** — exactly one meaningful brake active. Either CDI has started building (mediumness), or eCB has risen from sustained postsynaptic activity, but not both simultaneously. The system is aware something is happening but has not compounded yet. This is the normal operating range during moderate sustained firing.
- **Suppressed** — two brakes multiplying. The compounding is what defines this zone — no single variable alone produces it (except CDI approaching full). 0.5 × 0.5 = 0.25 remaining is where the synapse starts losing significant transmission efficacy. Biologically this is the pre-silence warning zone: CDI is building from residual Ca²⁺ while eCB is already engaged from postsynaptic activity. - **Suppressed** — two brakes multiplying. The compounding is what defines this zone — no single variable alone produces it (except CDI approaching full). 0.5 × 0.5 = 0.25 remaining is where the synapse starts losing significant transmission efficacy. Biologically this is the pre-silence warning zone: CDI is building from residual Ca2 while eCB is already engaged from postsynaptic activity.
- **Closed — CDI** = full is the only reliable hard rule. Because CDI can reach 1.0 and appears as (1 - CDI_factor) in the formula, it alone drives conductance to zero regardless of eCB and mGluR state. The three-brake overlap corner case (eCB=full + CDI=mediumness + mGluR=full) also reaches here, but in practice CDI reaching full is the primary biological mechanism. - **Closed — CDI** = full is the only reliable hard rule. Because CDI can reach 1.0 and appears as (1 - CDI_factor) in the formula, it alone drives conductance to zero regardless of eCB and mGluR state. The three-brake overlap corner case (eCB=full + CDI=mediumness + mGluR=full) also reaches here, but in practice CDI reaching full is the primary biological mechanism.
Devo controllare che le condizioni sotto siano esaustive. Qui ho confuso high con low, e inoltre ho messo NT per mGluR che devo controllare che abbia senso. Devo controllare che le condizioni sotto siano esaustive. Qui ho confuso high con low, e inoltre ho messo NT per mGluR che devo controllare che abbia senso.
##### Ca2+enterLow ##### Ca2enterLow
```Gen ```Gen
Ca2+enterLow Ca2enterLow
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ empty) AND (eCB empty) hypothesis: _Ca2 empty AND _eCB empty
action: [_Ca2+ increase, _ATP decrease] action: [ _Ca2 increase, _ATP decrease ]
trace: None trace: None
``` ```
##### Ca2+enterMedium ##### Ca2enterMedium
```Gen ```Gen
Ca2+enterMedium Ca2enterMedium
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ mediumness) OR hypothesis: _Ca2 mediumness OR
((eCB mediumness) AND (_Ca2+ empty)) OR ( _eCB mediumness AND _Ca2 empty ) OR
((eCB full) AND (_Ca2+ empty) AND (NT empty)) ( _eCB full AND _Ca2 empty AND _NT empty )
action: [_Ca2+ increase, _ATP decrease] action: [ _Ca2 increase, _ATP decrease ]
trace: None trace: None
``` ```
##### Ca2+enterHigh ##### Ca2enterHigh
```Gen ```Gen
Ca2+enterHigh Ca2enterHigh
type: accumulator
in_context: *AP in_context: *AP
hypothesis: (_Ca2+ mediumness) AND (eCB full) OR hypothesis: ( _Ca2 mediumness AND _eCB full ) OR
(eCB mediumness) _eCB mediumness
action: [_Ca2+ increase, _ATP decrease] action: [ _Ca2 increase, _ATP decrease ]
trace: None trace: None
``` ```
#### NOT *AP #### NOT *AP
Qui eliminiamo Ca2+. Il tempo che ci mette ad eliminare il Ca2+ dovrebbe essere minoe dell'inervallo fra un *AP e un'altra. Siccome non comprendiamo per ora _ATP, non c'e' accumulo di Ca2+ per mancanza di _ATP (stanchezza). Qui eliminiamo Ca2. Il tempo che ci mette ad eliminare il Ca2 dovrebbe essere minoe dell'inervallo fra un *AP e un'altra. Siccome non comprendiamo per ora _ATP, non c'e' accumulo di Ca2 per mancanza di _ATP (stanchezza).
Non non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA. Non comprendiamo per ora: Non non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA. Non comprendiamo per ora:
@@ -514,29 +533,31 @@ Non non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entrant
Qui disinguiamo: Qui disinguiamo:
- Ca+2 fullness che si puo' verificare alla fine di un AP - Ca+2 fullness che si puo' verificare alla fine di un AP
- NOT ca2+ fullness che svuota piu' lentamente - NOT Ca2 fullness che svuota piu' lentamente
- da capire se serve veramente questa distinzione per il tempo di svuotamento. - da capire se serve veramente questa distinzione per il tempo di svuotamento.
##### Ca2+ClearanceLow ##### Ca2ClearanceLow
```Gen ```Gen
Ca2+ClearanceLow Ca2ClearanceLow
type: accumulator
in_context: NOT *AP in_context: NOT *AP
hypothesis: (NOT _Ca2+ fullness) AND (NOT _Ca2+ empty) hypothesis: NOT _Ca2 fullness AND NOT _Ca2 empty
action: [_Ca2+ decrease] action: [ _Ca2 decrease ]
trace: None trace: None
``` ```
##### Ca2+ClearanceHigh ##### Ca2ClearanceHigh
```Gen ```Gen
Ca2+ClearanceHigh Ca2ClearanceHigh
type: accumulator
in_context: NOT *AP in_context: NOT *AP
hypothesis: NOT (Ca2+ empty) hypothesis: NOT _Ca2 empty
action: [Ca2+ decrease] action: [Ca2 decrease]
trace: None trace: None
``` ```