324 lines
12 KiB
Markdown
324 lines
12 KiB
Markdown
# BEH-AXO.md
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Qui comprendiamo:
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- BEH-AXO: Axon
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- BEH-PRE: Presynapse
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- BEH-VCGG: Voltage-Controlled Gated Channels
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## BEH-AXO: Container
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**Axon**: Axon does not contain specific behavior. We might add balancing of ATP within PRE later. Here we comprehend it as a “cable” transporting the AP from SOMA to Presynapse. It expands BEH-PRE which:
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- can be developed by DEV-PRE
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- the associations between BEH-PRE, BEH-POST e BEH-SYN is performed by the module that instantiate the Neurons and the Atrocytes, for example BEH-EXH or BEH-INH from winnertakeall.
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```Gen
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container: BEH-AXO
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expansion: BEH-PRE ( fullness: 50x, active: 0x, emptiness: 10x )
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# managed_by: BEH-EXH or BEH-INH from winnertakeall
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# developed_by: DEV-AXO-BEH-PRE-TUB from DEV-N
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```
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## BEH-PRE: Container
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**Presynapse:** We treat each presynapse as standalone. The vesicle reserve pool is a strictly private, local resource of each individual presynaptic bouton. What is shared between synapses on the same axon are signals (neuromodulators) and metabolic resources (energy), but not the synaptic vesicles themselves.
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**Behaviors**:
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---
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**Fast — ms**:
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- AP fires → membrane jumps to peak, decays toward rest (Na/K-ATPase recharge). Here we do not comprehend the decay.
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- ATP cost charged per AP (Here we can comprehend it with an integrator)
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- Ca²⁺ enters via VGCCs, gated by CDI, eCB, and mGluR suppression
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- ATP cost charged per unit Ca²⁺ cleared. Here we charge per Ca2+ entered
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- CDI (calcium-dependent inactivation of VGCCs)
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-- CDI rises with Ca2+ each ms: accumulates across inter-spike intervals under pump failure
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-- CDI recovers when Ca2+ is low: rate -> 0 when Ca2+ is high — the self-locking feedback
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- Ca²⁺ trace integrates toward CaTraces
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- Vesicles release from RRP, based on Ca2+ and RRP, suppressed by NT_cleft
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- NT added to cleft
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- NT_released_this_window accumulates (feeds Medium)
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- NT passively diffuses out of cleft (Astrocyte behavior)
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- Postsynaptic receptor activation and desensitization (Postsynaptic behavior)
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---
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**Medium — seconds**:
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- Astrocyte EAATs clear 30% of remaining NT_cleft (Astrocyte behavior)
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- IP3 integrates NT_released_this_window (cumulative burst load)
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- If IP3 exceeds threshold → astrocyte Ca²⁺ wave triggered
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- mGluR autoreceptor activation updates from NT_released_this_window
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- eCB retrograde signal updates from V_post history (from postsynapse)
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- RP → RRP recruitment runs (rate gated by CaTraces, costs ATP)
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---
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**Slow — mins**: Metabolic
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- Glucose level sets metabolic health
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- ATP_demand (accumulated from Loop 1) reduces ATP_level
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- conversion_efficiency written → gates glutamine shuttle
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- Glutamine shuttle refills N_RP from astrocyte store
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---
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**Tubs:**
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- **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 vescicles and modulation
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- **Rrp**: Readily Releasable Pool: The Readily Releasable Pool consists of the vesicles that are "docked" and "primed" at the active zone of the synapse.
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-- Location: Directly touching the presynaptic membrane.
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-- Function: These are the first to be released when an action potential arrives.
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-- Characteristics: 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.
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- **Rp**: The "Reserve Pool"
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-- Location: The bulk of the vesicles held further back in the terminal, often tethered by a protein called synapsin.
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-- Function: These are only mobilized during intense, prolonged stimulation once the RRP.
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-- Characteristics: This makes up the vast majority of the vesicles (up to 80% or 90%).
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- **Nt**: Neuro Transmitter, released in the synapse by the vescicles
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- **CaTraces**: sono le tracce di permanenza della concentrazione di Ca2+. Servono alla modulazione (TUN)
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```Gen
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container: BEH-PRE
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expansion: BEH-PRE-VGCC ( fullness: 10x, active: 5x, emptiness: 2x )
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# tuned_by: TUN-PRE-VGCC from TUN.N
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tub_local:
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- Ca2+ ( fullness: 60x, active: 30x, emptiness: 0x )
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# developed_by: DEV-PRE-CA2+FULL from DEV.N
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- Rrp ( fullness: 30x, active: 15x, emptiness: 0x )
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# developed_by: DEV-PRE-RRP-FULL from DEV.N
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- Rp ( fullness: 30x, active: 15x, emptiness: 0x )
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# developed_by: DEV-PRE-RRP-FULL from DEV.N
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- CaTraces ( fullness: 50x, active: 0x, emptiness: 0x )
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- mGluR ( fullness: 50x, active: 0x, emptiness: 0x )
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- CDI ( fullness: 50x, active: 0x, emptiness: 0x )
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tub_intricated:
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- NT # SYN
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- ATP # AXO?
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- eCB # from POST
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context_intricated:
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- AP ( contained_by: BEH-SOMA )
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```
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### ms: behavior
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#### RRPConcentration: Context
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Il rilascio di NT lo facciamo nel contesto di AP. Biologicamente dovrebbe avvenire solo in base alle concentrazioni, quindi anche al difuori degli AP.
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```Gen
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context: RRPConcentration
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contained_by: BEH-PRE
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in_context: AP
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rf: ( active: 60x )
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condition: (Rrp medium)
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out_context: RRPMedium
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condition: (Rrp full)
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out_context: RRPFull
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```
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#### Ca2+Concentration: Context
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```Gen
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context: Ca2+Concentration
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contained_by: BEH-PRE
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in_context: AP
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rf: ( active: 60x )
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condition: (Ca2+ medium)
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out_context: Ca2+Medium
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condition: (Ca2+ full)
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out_context: Ca2+Full
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```
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#### NTrelease: Episodes
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Ci sono 4 casi che dipendono da RRP, Ca2+ e NT. L'idea e' che la quantita' di RRP sia il driver principale. Gli NT liberati sono di piu' al crescere di RRP e Ca2+ e di meno al crescere di NT. Gli NT nella sinapsi fanno da moderazione alla ulteriore liberazione di NT, ma non bloccano mai totalmente. NT suppression only matters when everything else is already at maximum — which is exactly the biological purpose: it prevents runaway release during peak activity, not during moderate activity.
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ATP cost of Na/K-ATPase recharge on each AP. The cost is per action potential. Here we charge it at every release of NT. This is the dominant ATP drain at high firing rates.
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##### NTreleaseMaximum: Episode
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```Gen
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episode: NTreleaseMaximum
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contained_by: BEH-PRE
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in_context: (Ca2+Full AND RRPFull)
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rf: ( active: 6x ) # Maximum
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hypothesis: (NT empty)
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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##### NTreleaseHigh: Episode
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```Gen
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episode: NTreleaseHigh
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contained_by: BEH-PRE
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in_context: (Ca2+Full AND RRPFull)
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rf: ( active: 6x ) # High
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hypothesis: NOT (NT empty) # solo in questo caso NT modera!
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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##### NTreleaseMedium: Episode
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```Gen
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episode: NTreleaseMedium
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contained_by: BEH-PRE
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in_context: (Ca2+Full AND RRPMedium) OR (Ca2+Medium AND RRPFull)
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rf: ( active: 6x ) # Medium
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hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
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action: [Rrp decrease, Nt increase, ATP decrease]
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trace: None
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```
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##### NTreleaseLow: Episode
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```Gen
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episode: NTreleaseLow
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contained_by: BEH-PRE
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in_context: (Ca2+Medium AND RRPMedium)
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rf: ( active: 6x ) # Low
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hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
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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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#### CaClearance
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Qui eliminiamo Ca2+. Non comprendiamo per ora:
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- PMCA: primary, ATP-dependent
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- NCX: fast, NOT ATP-dependent
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- SERCA: slowest, ATP-dependent
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Quindi non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA.
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### sec: behavior
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...
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#### mGlur concentration
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Limita rilascio NT: Dipende da quanti NT sono stati gia' rilasciati nella Syn
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#### eCB concentration
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Limita rilascio NT: Dipende da POST che tende a bloccare rialascio di NT se non servono
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#### CaTrace concentration
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Serve a dare la velocita' al trasporto di vesicles da RP a RRP. Ha un decadimento proprio il che dice alla Presinapsi di accellerare se da poco c'e' stata una spike, altrimenti di andare piu' piano. So after one second of silence Tr_Ca has fallen to ~37% of its peak value, after two seconds to ~14%, after three seconds to ~5%. It asymptotes toward zero but never exactly reaches it. Between spikes, Ca2+ falls toward zero as the pumps clear it.
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#### RP->RRP shuttling
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Dipende da?
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### min: behavior
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#### Refill RP from Glutamine
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Dipende da Glutamine messa a disposizione dall'Astrocyte
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## BEH-PRE-VGCC: Container
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**Voltage-Controlled Gated Channels**:
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Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.
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```Gen
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container: BEH-PRE-VGCC
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tub_intricated:
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- Ca2+ ( contained_by: BEH-PRE )
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context_intricated:
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- AP ( contained_by: BEH-SOMA )
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```
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### Ca2+enter: Episodes
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Here we comprehend the breaking activity on VGCC by: CDI,eCB and mGluR:
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- **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.
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- **Reduced/partial** — exactly one meaningful brake active. Either CDI has started building (medium), 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.
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- **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.
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- **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=medium + mGluR=full) also reaches here, but in practice CDI reaching full is the primary biological mechanism.
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Qui sostituiamo il CDI con Ca2+:
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- 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.
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- 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.
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Devo controllare che le condizioni sotto siano esaustive.
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#### Open: Episode
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```Gen
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episode: Open
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contained_by: BEH-PRE-VGCC
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in_context: AP
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rf: ( active: 6x )
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hypothesis: (Ca2+ empty) and (eCB empty)
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action: [Ca2+ increase, ATP decrease]
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trace: None
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```
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#### Reduced-partial: Episode
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```Gen
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episode: Reduced-partial
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contained_by: BEH-PRE-VGCC
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in_context: AP
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rf: ( active: 6x )
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hypothesis: (Ca2+ medium) OR ((eCB medium) AND (Ca2+ empty)) OR ((eCB full) AND (Ca2+ empty) AND (mGluR empty))
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action: [Ca2+ increase, ATP decrease]
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trace: None
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```
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#### Suppressed: Episode
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```Gen
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episode: Supressed
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contained_by: BEH-PRE-VGCC
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in_context: AP
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rf: ( active: 6x )
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hypothesis: ((Ca2+ medium) AND (eCB full) OR (eCB medium))
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action: [Ca2+ increase, ATP decrease]
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trace: None
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```
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