organism/neuron/BEH-AXO.md

# BEH-AXO.md

Qui comprendiamo:

- BEH-AXO: Axon
- BEH-PRE: Presynapse
- BEH-VCGG: Voltage-Controlled Gated Channels

## BEH-AXO: Container

**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:

- can be developed by DEV-PRE
- 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.

```Gen
container: BEH-AXO

  expansion: BEH-PRE ( fullness: 50x, active: 0x, emptiness: 10x ) 
    # managed_by: BEH-EXH or BEH-INH from winnertakeall
    # developed_by: DEV-AXO-BEH-PRE-TUB from DEV-N
```

## BEH-PRE: Container

**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.

**Behaviors**:

---

**Fast — 1 ms**:

- AP fires → membrane jumps to peak, decays toward rest (Na/K-ATPase recharge). Here we do not comprehend the decay.
- ATP cost charged per AP
- Ca²⁺ enters via VGCCs, gated by CDI, eCB, and mGluR suppression
- ATP cost charged per unit Ca²⁺ cleared. Here we charge per Ca2+ entered
- CDI rises with Ca²⁺, recovers when Ca²⁺ is low
- Ca²⁺ trace integrates toward Tr_Ca
- Vesicles release from RRP, based on CaMicro and RRP, suppressed by NT_cleft
- NT added to cleft
- NT_released_this_window accumulates (feeds Medium)
- NT passively diffuses out of cleft (Astrocyte behavior)
- Postsynaptic receptor activation and desensitization (Postsynaptic behavior)

---

**Medium — 1 s**:

- Astrocyte EAATs clear 30% of remaining NT_cleft (Astrocyte behavior)
- IP3 integrates NT_released_this_window (cumulative burst load)
- If IP3 exceeds threshold → astrocyte Ca²⁺ wave triggered
- mGluR autoreceptor activation updates from NT_released_this_window
- eCB retrograde signal updates from V_post history (from postsynapse)
- RP → RRP recruitment runs (rate gated by Tr_Ca, costs ATP)

---

**Slow — 1 min**: Metabolic

- Glucose level sets metabolic health
- ATP_demand (accumulated from Loop 1) reduces ATP_level
- conversion_efficiency written → gates glutamine shuttle
- Glutamine shuttle refills N_RP from astrocyte store

---

**Actors**:

- CDI (calcium-dependent inactivation of VGCCs)
-- CDI rises with Ca_micro each ms: accumulates across inter-spike intervals under pump failure
-- CDI recovers when Ca_micro is low: rate -> 0 when Ca_micro is high — the self-locking feedback

---

**Tubs:**

- **Ca2+**: Calcium Ion entering the Presynapse when VCGG open.
- **Ca2Micro**: free cytosolic Ca2+ in microdomain 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
- **Rrp**: Readily Releasable Pool: The Readily Releasable Pool consists of the vesicles that are "docked" and "primed" at the active zone of the synapse.  
-- Location: Directly touching the presynaptic membrane.  
-- Function: These are the first to be released when an action potential arrives.  
-- 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.
- **ReservePool**: The "Reserve Pool"
-- Location: The bulk of the vesicles held further back in the terminal, often tethered by a protein called synapsin.  
-- Function: These are only mobilized during intense, prolonged stimulation once the RRP.  
-- Characteristics: This makes up the vast majority of the vesicles (up to 80% or 90%).
- **Nt**: Neuro Transmitter, released in the synapse by the vescicles
- **CaTraces**: sono le tracce di permanenza della concentrazione di Ca2+. Servono alla modulazione (TUN)

```Gen
container: BEH-PRE

  expansion: BEH-PRE-VGCC ( fullness: 10x, active: 5x, emptiness: 2x )
              # tuned_by: TUN-PRE-VGCC from TUN.N

  tub_local:
    - Ca2+ ( fullness: 60x, active: 30x, emptiness: 0x )
       # developed_by: DEV-PRE-CA2+FULL from DEV.N

    - CaMicro ( fullness: 60x, active: 30x, emptiness: 0x )

    - Rrp ( fullness: 30x, active: 15x, emptiness: 0x )
       # developed_by: DEV-PRE-RRP-FULL from DEV.N

    - Rp ( fullness: 30x, active: 15x, emptiness: 0x )
       # developed_by: DEV-PRE-RRP-FULL from DEV.N

    - CaTraces ( fullness: 50x, active: 0x, emptiness: 0x )

  tub_intricated:
    - NT
    - ATP

  context_intricated:
  - AP ( contained_by: BEH-SOMA ) 

```

### RRPConcentration: Context

Il rilascio di NT lo facciamo nel contesto di AP. Biologicamente dovrebbe avvenire solo in base alle concentrazioni, quindi anche al difuori degli AP.

```Gen
context: RRPConcentration
  contained_by: BEH-PRE

  in_context: AP
  rf: ( active: 60x )

  condition: NOT (Rrp empty) AND NOT (Rrp full) 
    out_context: RRPMedium

  condition: (Rrp full) 
    out_context: RRPFull
```

### Ca2MicroConcentration: Context

```Gen
context: Ca2MicroConcentration
  contained_by: BEH-PRE

  in_context: AP
  rf: ( active: 60x )

  condition: NOT (Ca2Micro empty) AND NOT (Ca2Micro full) 
    out_context: Ca2MicroMedium

  condition: (Ca2Micro full) 
    out_context: Ca2MicroFull
```

### NTrelease episodes

Ci sono 4 casi che dipendono da RRP, CaMicro 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 CaMicro 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.

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.

#### NTreleaseMaximum episodes

```Gen
episode: NTreleaseMaximum
  contained_by: BEH-PRE

  in_context: (Ca2MicroFull AND RRPFull)
  rf: ( active: 6x ) # Maximum

  hypothesis: (NT empty)
    action: [Rrp decrease, Nt increase, ATP decrease]
    trace: None
```

#### NTreleaseHigh episodes

```Gen
episode: NTreleaseHigh
  contained_by: BEH-PRE

  in_context: (Ca2MicroFull AND RRPFull)
  rf: ( active: 6x ) # High

  hypothesis: NOT (NT empty) # solo in questo caso NT modera!
    action: [Rrp decrease, Nt increase, ATP decrease]
    trace: None
```

#### NTreleaseMedium episodes

```Gen
episode: NTreleaseMedium
  contained_by: BEH-PRE

  in_context: (Ca2MicroFull AND RRPMedium) OR (Ca2MicroMedium AND RRPFull)
  rf: ( active: 6x ) # Medium

  hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
    action: [Rrp decrease, Nt increase, ATP decrease]
    trace: None
```

#### NTreleaseLow episodes

```Gen
episode: NTreleaseLow
  contained_by: BEH-PRE

  in_context: (Ca2MicroMedium AND RRPMedium)
  rf: ( active: 6x ) # Low

  hypothesis: (NT empty) OR NOT (NT empty) # In tutti i casi
    action: [Rrp decrease, Nt increase, ATP decrease]
    trace: None
```

## BEH-PRE-VGCC: Container

**Voltage-Controlled Gated Channels**:
Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.

```Gen
container: BEH-PRE-VGCC

  tub_intricated:
   - Ca2+ ( contained_by: BEH-PRE )

 context_intricated:
    - AP ( contained_by: BEH-SOMA )
```