diff --git a/elements/neuron/presynapse.md b/elements/neuron/presynapse.md index 0d0d314..b918660 100644 --- a/elements/neuron/presynapse.md +++ b/elements/neuron/presynapse.md @@ -9,22 +9,22 @@ Qui comprendiamo: - PRESYNAPSE: Presynapse - VGCC-PRE: Voltage-Controlled Gated Channels -## PRESYNAPSE +## {PRESYNAPSE} ```Gen -PRESYNAPSE +{PRESYNAPSE} type: comprehension expand_comprehension: - _VgccPre: VGCC-PRE [ full: 10x, active: 5x, empty: 2x ] + _VgccPre: {VGCC-PRE} [ full: 10x, active: 5x, empty: 2x ] instantiate_container: - @: $BehaviorPre [] - @: $TunVgccPre [pass: _VgccPre] + BEHAVIOR_PRE: CONTAINER [] + TUNE_VGCC_PRE: CONTAINER [pass: _VgccPre] ``` -### $BehaviorPre +### BEHAVIOR_PRE **Tubs:** @@ -36,10 +36,10 @@ PRESYNAPSE - **_eCB**: retrograde signal updates from postsynapsis (postsynaptic input) ```Gen -$BehaviorPre +BEHAVIOR_PRE - type: container activity_scope: !DAY + type: container tub_local: _Ca2+: TUB [ full: 60x, active: 30x, empty: 0x ] @@ -58,16 +58,26 @@ $BehaviorPre snippets: # &AP - NTreleaseLow: [RF: active 12x, type: accumulator] - NTreleaseMedium [RF active 9x, type: accumulator] - NTreleaseHigh: [RF active 9x, type: accumulator] + NTreleaseLow: ACCUMULATOR [RF: active 12x] + NTreleaseMedium: ACCUMULATOR [RF active 9x] + NTreleaseHigh: ACCUMULATOR [RF active 9x] - Ca2+TracesAccLow: [RF active 3x, type: accumulator] - Ca2+TracesAccMedium: [RF active 6x, type: accumulator] - Ca2+TracesAccHigh: [RF active 10x, type: accumulator] + Ca2+TracesAccLow: ACCUMULATOR [RF active 3x] + Ca2+TracesAccMedium: ACCUMULATOR [RF active 6x] + Ca2+TracesAccHigh: ACCUMULATOR [RF active 10x] # NOT &AP - eCBClearence: RF [active: 24x] + eCBClearenceMedium: ACCUMULATOR [RF: active: 24x] + eCBClearenceLow: ACCUMULATOR [RF: active: 248x] + + RPShuttleLow: ACCUMULATOR [RF: active: 24x] + RPShuttleMedium: ACCUMULATOR [RF: active: 48x] + + RefillGlutamine: ACCUMULATOR [RF: active: 24x] + + Ca2+TracesClearance: ACCUMULATOR [RF: active: 30x] + + ``` #### &AP @@ -94,6 +104,7 @@ In tutti i casi di NT NTreleaseLow in_context: &AP + hypothesis: ( _Ca2+ mediumness ) AND ( _Rrp mediumness ) AND NOT( _ATP empty ) action: [_Rrp decrease, _Nt increase, _ATP decrease] trace: None @@ -104,7 +115,8 @@ NTreleaseLow ```Gen NTreleaseMedium - in_context: AP_ctx + in_context: &AP + hypothesis: (( Ca2+ fullness ) AND ( Rrp mediumness ) OR ( Ca2+ mediumness ) AND ( Rrp fullness )) AND NOT( ATP empty ) @@ -117,7 +129,8 @@ NTreleaseMedium ```Gen NTreleaseHigh - in_context: AP_ctx + in_context: &AP + hypothesis: ( Ca2+ fullness ) AND ( Rrp fullness ) AND NOT( ATP empty ) action: [Rrp decrease, NT increase, ATP decrease] @@ -130,16 +143,17 @@ Serve a: - fare il tuning dei VGCC - dare la velocita' al trasporto di vesicles da RP a RRP, anche se non avendo ancora compreso ATP, la velocita' non cambia molto la sostanza. -- le tracce vengono eliminate quando il neurone e' in pausa, lontano da uno spike train, TunPossible_ctx +- le tracce vengono eliminate quando il neurone e' in pausa, lontano da uno spike train, &TunePossible - 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_ctx 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. - 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 Ca2+TracesAccuLow - in_context: AP_ctx + in_context: &AP + hypothesis: (Ca2+ emptiness) action: [CaTraceLow increase] trace: None @@ -150,7 +164,8 @@ Ca2+TracesAccuLow ```Gen Ca2+TracesAccMedium - in_context: AP_ctx + in_context: &AP + hypothesis: (Ca2+ mediumness) action: [CaTraceMed increase] trace: None @@ -161,7 +176,8 @@ Ca2+TracesAccMedium ```Gen Ca2+TracesAccumulationHigh - in_context: AP_ctx + in_context: &AP + hypothesis: (Ca2+ fullness) action: [CaTraceHigh increase] trace: None @@ -169,26 +185,23 @@ Ca2+TracesAccumulationHigh #### NOT &AP -##### eCB clearance: accumulator +##### 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 RF di questo episodio. -##### eCBClearance: ( active: 24x ) accumulator - ```Gen eCBClearance: ( active: 24x ) # Slow - type: accumulator - contained_by: PRESYNAPSE-BEH - in_context: NOT AP_ctx + in_context: NOT &AP + hypothesis: NOT (eCB empty) action: [eCB decrease] trace: None ``` -##### RPShuttleLow: ( active: 48x ) accumulator +##### RPShuttleLow This happens in the seconds loop, once per second. @@ -197,11 +210,10 @@ The "Hard Bottleneck" State. Recruitment is throttled by a lack of signal, a lac Rate: 0.00 – 0.25 ```Gen -RPShuttleLow: ( active: 48x ) # Low - type: accumulator - contained_by: PRESYNAPSE-BEH +RPShuttleLow + + in_context: NOT &AP - in_context: NOT AP_ctx hypothesis: (CaTraceLow fullness) OR (RP emptiness) OR (RRP fullness) @@ -209,18 +221,17 @@ RPShuttleLow: ( active: 48x ) # Low trace: None ``` -##### RPShuttleMedium: ( active: 24x ) accumulator +##### 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 ```Gen -RPShuttleMedium: ( active: 24x ) # Medium - type: accumulator - contained_by: PRESYNAPSE-BEH +RPShuttleMedium + + in_context: &AP - in_context: AP_ctx 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 @@ -229,18 +240,17 @@ RPShuttleMedium: ( active: 24x ) # Medium trace: None ``` -##### RPShuttleHigh: ( active: 12x ) accumulator +##### 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 ```Gen -RPShuttleHigh: ( active: 12x ) # Fast - type: accumulator - contained_by: PRESYNAPSE-BEH +RPShuttleHigh + + in_context: &AP - in_context: AP_ctx 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 @@ -248,7 +258,7 @@ RPShuttleHigh: ( active: 12x ) # Fast trace: None ``` -##### RefillRPGlutamine: accumulator +##### 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. @@ -278,16 +288,15 @@ 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. -##### Ca2+TracesClearance: ( active: 30x ) accumulator +##### Ca2+TracesClearance Qui facciamo un flush di CaTraceX. Deve essere fatto a valle del tuning. ```Gen -Ca2+TracesClearance: ( active: 30x ) # Slow - type: accumulator - contained_by: PRESYNAPSE-BHE +Ca2+TracesClearance + + in_context: NOT &TunePossible - in_context: NOT TunPossible_ctx hypothesis: NOT (CaTraceHigh empty) action: [CaTRaceHigh decrease] trace: None @@ -301,41 +310,45 @@ Ca2+TracesClearance: ( active: 30x ) # Slow trace: None ``` -### VGCC-PRE-TUN: Container +### TUNE_VGCC_PRE ```Gen -VGCC-PRE-TUN +TUNE_VGCC_PRE # 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. - type: container activity_scope: !DAY + type: container context_intricated: - - TunPossible_ctx ( contained_by: DAY-N ) + - &TunePossible ( contained_by: DAY-N ) tub_passed: - VGCC-PRE_ALL: pass.VGCC-PRE_ALL + _VgccPre: pass._VgccPre tub_local: tub_intricated: + snippets: + + CheckVgccPreTun: CONTEXTOR [RF: active 60x] + PossibleUpPreVgccTun: ACCUMULATOR [RF:active 10x] + PossibleDownPreVgccTun: ACCUMULATOR [RF:active 10x] ``` -#### TunPossible_ctx +#### &TunePossible -##### CheckVgccPreTun: ( active: 60x ) contexting +##### CheckVgccPreTun Qui controlliamo che ci siano le condizioni per aumentare o diminuire la quantita' di VGCC ```Gen -CheckVgccPreTun: ( active: 60x ) - type: contexting - contained_by: VGCC-PRE-TUN +CheckVgccPreTun + + in_context: &TunePossible - in_context: TunPossible_ctx condition: ( CaTraceHigh fullness ) out_context: TryTunUpPreVcgg_ctx @@ -343,14 +356,13 @@ CheckVgccPreTun: ( active: 60x ) out_context: TryTunDownPreVcgg_ctx ``` -##### PossibleUpPreVgccTun: ( active: 10x ) accumulator +##### PossibleUpPreVgccTun ```Gen -PossibleUpPreVgccTun: ( active: 10x ) - type: accumulator - contained_by: VGCC-PRE-TUN +PossibleUpPreVgccTun in_context: TryTunUpPreVcgg_ctx + hypothesis: action: trace: @@ -359,37 +371,36 @@ PossibleUpPreVgccTun: ( active: 10x ) ##### PossibleDownPreVgccTun: ( active: 10x ) accumulator ```Gen -PossibleDownPreVgccTun: ( active: 10x ) - type: accumulator - contained_by: VGCC-PRE-TUN +PossibleDownPreVgccTun in_context: TryTunDownPreVcgg_ctx + hypothesis: action: trace: ``` -## VGCC-PRE: Comprehension +## {VGCC-PRE} Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare. ```Gen -VGCC-PRE +{VGCC-PRE} type: comprehension instantiate_container: - VGCC-PRE-BEH [] + BEHAVIOR_VGCC_PRE: CONTAINER [] ``` -### VGCC-PRE-BEH: Container +### BEHAVIOR_VGCC_PRE Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare. ```Gen -VGCC-PRE-PRE +BEHAVIOR_VGCC_PRE - type: container activity_scope: !DAY + type: container tub_intricated: - Ca2+ ( contained_by: PRESYNAPSE-BHE ) @@ -397,9 +408,19 @@ VGCC-PRE-PRE context_intricated: - AP ( contained_by: SOMA ) + + snippets: + + Ca2+enterLow: ACCUMULATOR [RF: active 12x] + Ca2+enterMedium: ACCUMULATOR [RF: active 6x] + Ca2+enterHigh: ACCUMULATOR [RF: active 3x] + + Ca2+ClearanceLow: ACCUMULATOR [RF: active 24x] + Ca2+ClearanceHigh: ACCUMULATOR [RF: active 4x] + ``` -#### AP_ctx +#### &AP Da rivedere le condizioni per aggiungere mGluR che ha come proxy NT concentration!!!!! @@ -421,27 +442,25 @@ Qui semplifichiamo: 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: ( active: 12x ) accumulator +##### Ca2+enterLow ```Gen -Ca2+enterLow: ( active: 12x ) # Low - type: accumulator - contained_by: VGCC-PRE-BEH +Ca2+enterLow + + in_context: &AP - in_context: AP_ctx hypothesis: (Ca2+ empty) AND (eCB empty) action: [Ca2+ increase, ATP decrease] trace: None ``` -##### Ca2+enterMedium: ( active: 6x ) accumulator +##### Ca2+enterMedium ```Gen -Ca2+enterMedium: ( active: 6x ) # Medium - type: accumulator - contained_by: VGCC-PRE-BEH +Ca2+enterMedium + + in_context: &AP - in_context: AP_ctx hypothesis: (Ca2+ mediumness) OR ((eCB mediumness) AND (Ca2+ empty)) OR ((eCB full) AND (Ca2+ empty) AND (NT empty)) @@ -449,23 +468,22 @@ Ca2+enterMedium: ( active: 6x ) # Medium trace: None ``` -##### Ca2+enterHigh: ( active: 3x ) accumulator +##### Ca2+enterHigh ```Gen -Ca2+enterHigh: ( active: 3x ) # High - type: accumulator - contained_by: VGCC-PRE-BEH +Ca2+enterHigh + + in_context: &AP - in_context: AP_ctx hypothesis: (Ca2+ mediumness) AND (eCB full) OR (eCB mediumness) action: [Ca2+ increase, ATP decrease] trace: None ``` -#### NOT AP_ctx +#### NOT &AP -Qui eliminiamo Ca2+. Il tempo che ci mette ad eliminare il Ca2+ dovrebbe essere minoe dell'inervallo fra un AP_ctx 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: @@ -479,27 +497,25 @@ Qui disinguiamo: - NOT ca2+ fullness che svuota piu' lentamente - da capire se serve veramente questa distinzione per il tempo di svuotamento. -##### Ca2+ClearanceLow: ( active: 24x ) accumulator +##### Ca2+ClearanceLow ```Gen -Ca2+ClearanceLow: ( active: 24x ) # Low - type: accumulator - contained_by: VGCC-PRE-BEH +Ca2+ClearanceLow + + in_context: NOT &AP - in_context: NOT AP_ctx hypothesis: (NOT Ca2+ fullness) AND (NOT Ca2+ empty) action: [Ca2+ decrease] trace: None ``` -##### Ca2+ClearanceHigh: ( active: 4x ) accumulator +##### Ca2+ClearanceHigh ```Gen -Ca2+ClearanceHigh: ( active: 4x ) # High - type: accumulator - contained_by: VGCC-PRE-BEH +Ca2+ClearanceHigh + + in_context: NOT &AP - in_context: NOT AP_ctx hypothesis: NOT (Ca2+ empty) action: [Ca2+ decrease] trace: None