organism/neuron/soma.md

# soma.md

Qui comprendiamo:

- SOMA: il soma
- VGSC-SOMA-H: Na ion channels. Open only when VDB high
- VGSC-SOMA-M: Na ion channels. Open only when VDB medium
- VGSC-SOMA-L: Na ion channels. Open only when VDB low

## SOMA: container

---

**Simplified verifiable behaviors**:

— ms:

- Resting at -70 mV: Leak channels + pumps (keep at resting)
- VDB Depolarization : ~1-2 ms: Na⁺ enters (some VGSCs open)
- Opened VGSC and then remain closed for a refractory period
- Spike if depolarized above threshold: to -50 mV
- Ca2+ enter
- Repolarization to -70 mV:  ~1-2 ms: K⁺ exits (VG K⁺ channels open) ← NOT pumps!
- After-hyperpolarization: ~5-20 ms: K⁺ channels still open

— secs:

- Return to exact -70 mV: ~100-1000 ms: Na⁺/K⁺ pumps restore gradients
- Ca2+ accumulation

— mins:

- VGSC modulation

---

**G expression**:

— ms:

- based on VDB, VGSC open and let Na+ in. VGSG then go into refractory
- if Na fullness then ApCtx. Here the threshold is based only on the integration of Na+
- increase SpikeTrainTraces (fast at spike)
- increase Ca2+ traces
- decrease Na: fast pump which decreases Na+, we do not model K+
-- there is a tug of war between Na entering and exiting. Na can reach fullness only if VDB increases fast (derivative)
- there are 2 context: ApCtx and RefractorySoma imlemented with timers and tunable
- decrease SpikeTraintraces slow, only if away from spiketrain this is empty

- Tune:
-- The threshold is tuned during the spiketrain. Low threshold at rest, to increase sensitivity, threshold increase during spike to increase discrimination

— secs:

- SpikeTrainTraces

— mins:

- Tune:
-- refractory lenght

---

**Tubs:**

- **VDB**: dendrites deliver current

- **Na**: are a proxy for the Coulombs of charge building up on the somatic membrane. They are used to check threshold, but also to mimic Na+ and K+ pumping

- **Ca2+**: Medium term traces to guide tuning and Night development. It is a local trace, ATP is a global (Astrocyte)

- **SpikeTrainTraces**: sono le tracce che consentono al neurone di far partire il Tuning neuronale, quando e' lontano da uno spike-train, ovvero e' in riposo.

- **RefractorySoma**: tracce di refractory

---

```Gen
container: SOMA

  expansion: 
    - VGSC-SOMA-H ( full: 50x, active: 20x, empty: 10x ) 
      # modulated_by: VGSC-SOMA-H-TUN # possible/actual

    - VGSC-SOMA-M ( full: 50x, active: 20x, empty: 10x ) 
      # modulated_by: VGSC-SOMA-M-TUN # possible/actual

    - VGSC-SOMA-L ( full: 50x, active: 20x, empty: 10x ) 
      # modulated_by: VGSC-SOMA-L-TUN # possible/actual


  tub_local:
    - VDB
    - Na
    - Ca2+
    - RefractorySoma

  tub_intricated:  
    - SpikeTrainTraces ( contained_in: DAY-N )
```

### ms: SOMA

#### SOMA-Status: contextor

As dendrites deliver current (VDB​), the soma acts like a capacitor. It "stores" this charge in the form of membrane potential. This contextualizes VGSC-SOMA to open ion channels that let Na+ ions in.

This only applies if not ApCtx, or in other words, SOMA is not in refractory period.

```Gen
SOMA-Status: ( active: 60x )
  type: contextor
  contained_by: SOMA

  in_context: any

  condition: ( VDB fullness ) AND NOT AP_ctx
    out_context: VDBMax_Ctx

  condition: ( VDB mediumness ) AND NOT AP_ctx
    out_context: VDBMedium_ctx 

  condition: ( VDB emptiness ) AND NOT Ap_ctx
    out_context: VDBLow_ctx

  condition: NOT ( Na empty )
    out_context: NaSpill_ctx

  condition: NOT ( RefractorySoma empty )
    out_context: RefractorySoma_ctx
```

#### SomaSpike: contextor

Il fatto che mettiamo il check di AP separato dal check del Soma-Status, e' perche' vogliamo poter avere un RF specifico per AP, eventualmente tunabile.

Qui siamo nella fase effettiva di spike, non refractory che viene dopo. Fa da contesto di durata fra un RF ed un altro.

La fullness di Na rappresenta il threshold e puo' essere modificato. La fullness di RefractorySoma rappresenta la lunghezza del refractory.

```Gen
SomaSpike: ( active: 30x )
  type: contextor
  contained_by: SOMA

  in_context: any
    condition: ( Na fullness ) AND ( RefractorySoma emptiness )
      out_context: AP_ctx
      out_context: bAp_ctx
```

#### ActiveAP: accumulator

Durante la fase effettiva di spike:

- eliminiamo Na accumulati. Qui ad un RF molto maggiore che con NaSpill. In teoria qui dovremmo eliminare tutti gli Na e NaSpill potrebbe non servire.
- riempiamo RefractorySoma per fase di refractory
- riempiamo Ca2+ per le tracce medio termine di potenziamento/depotenziamento.

```Gen
ActiveAP: ( active: 8x )
  type: accumulator
  contained_by: SOMA

  in_context: Ap_ctx
    hypothesis: NOT Na empty
      action: [ decrease Na ]
      trace: 

    hypothesis: NOT RefractorySoma full
      action: [ increase RefractorySoma ]
      trace: 

    hypothesis: NOT Ca2+ full
      action: [ increase Ca2+ ]
      trace: 
```

#### NaSpill: accumulator

Questo potrebbe non servire se eliminiamo tutti Na durante ActiveAP.

```Gen
NaSpill: ( active: 8x )
  type: accumulator
  contained_by: SOMA

  in_context: NaSpill_ctx
    hypothesis: NOT ( Na emptiness )
      action: [ decrease Na ]
      trace:
```

#### RefractorySomaSpill: accumulator

Lo spill deve essere piu' lento dell'increase che avviene in ActiveAP

```Gen
RefractorySomaSpill: ( active: 16x )
  type: accumulator
  contained_by: SOMA

  in_context: RefractorySoma_ctx
    hypothesis: NOT ( RefractorySoma empty )
      action: [ decrease RefractorySoma ]
      trace: 
```

### sec: SOMA

### min: SOMA

## VGSC-SOMA-H: container

Voltage Gated Sodium Channel: difficult to open (High)

```Gen
container: VGSC-SOMA-H

  tub_local:
    RefractoryH ( full: 60x, active: 30x, empty: 0x )

  tub_intricated:
    Na ( contained_in: SOMA)

   context_intricated:
    VDBMaxCtx ( contained_by: SOMA )
```

### sec: VGSC-SOMA-H

#### VGSC-H_Status: contextor

Il check su refractory deve essere fatto ad un RF maggiore della eliminazione di Refractory. Questo perche' e' un era nella quale avviene l'episodio.

```Gen
VGSC-H_Status: ( active: 60x )
  type: contextor
  contained_by: VGSC-SOMA-H

  in_context: any
    condition: VDBMaxCtx AND ( RefractoryH emptiness ) 
      out_context: NaEnterH_Ctx

    condition: ( RefractoryH mediumness ) OR ( RefractoryH fullness )
      out_context: RefractoryHSpill_ctx
```

#### NaEnterH: accumulator

Se metto il controllo sulla (NOT Ready fullness) il VGSC puo' far entrare un numero di Na non superiore ad un massimo.
Questo sopra è il commmento della versione precedente, ora la quantità di NA increase dipende dal rf di VGSC-H_TPC dato che li c'è la condition sulla presenza delle traccie di refractory

```Gen
NaEnterH: ( active: 1x )
  type: accumulator
  contained_by: VGSC-SOMA-H

  in_context: NaEnterH_ctx
    hypothesis: ( NOT Na full )
      action: [ Na increase]
      trace: None

    hypothesis: ( NOT RefractoryH full )
      action: [ RefractoryH increase ]
      trace: None
```

#### RefractoryHSpill: accumulator

Lo Spill deve avere un rf maggiore dell'interacting che incrementa RefractoryH (interactor precedente)

```Gen
RefractoryHSpill: ( active: 1x )
  type: accumulator
  contained_by: VGSC-SOMA-H

  in_context: RefractoryHSpill_ctx
    hypothesis: NOT ( RefractoryH empty )  
      action: [ RefractoryH decrease ]
      trace: None
```

## VGSC-SOMA-M: container

Voltage Gated Sodium Channel: less difficult to open (Medium)

```Gen
container: VGSC-SOMA-M

  tub_local:
    RefractoryM ( full: 60x, active: 30x, empty: 0x )

  tub_intricated:
    Na ( contained_in: SOMA)

  context_intricated:
    VDBMedCtx ( contained_by: SOMA ) 
```

### sec: VGSC-SOMA-M

#### VGSC-M_TPC: contextor

Il check su refractory deve essere fatto ad un RF maggiore della eliminazione di Refractory. Questo perche' e' un era nella quale avviene l'episodio.

```Gen
VGSC-M_Status: ( active: 60x )
  type: contextor
  contained_by: VGSC-SOMA-M

  in_context: VDBMediumCtx OR VDBMaxCtx
    condition: ( RefractoryH emptiness ) 
      out_context: NaEnterM_Ctx
```

#### NaEnterM: accumulator

Se metto il controllo sulla (NOT Ready fullness) il VGSC puo' far entrare un numero di Na non superiore ad un massimo.
Questo sopra è il commmento della versione precedente, ora la quantità di NA increase dipende dal rf di VGSC-H_TPC dato che li c'è la condition sulla presenza delle traccie di refractory

```Gen
NaEnterM: ( active: 1x )
  type: accumulator
  contained_by: VGSC-SOMA-M

  in_context: NaEnterM_ctx
    hypothesis: ( NOT Na full )
      action: [ Na increase]
      trace: None

    hypothesis: ( NOT RefractoryM full )
      action: [ RefractoryH increase ]
      trace: None
```

#### RefractoryMSpill: accumulator

Lo Spill deve avere un rf maggiore dell'interacting che incrementa RefractoryH (interactor precedente)

```Gen
RefractoryMSpill: ( active: 1x )
  type: accumulator
  contained_by: VGSC-SOMA-M

  in_context: any
    hypothesis: NOT ( RefractoryM empty )  
      action: [ RefractoryM decrease ]
      trace: None
```

## VGSC-SOMA-L: container

Voltage Gated Sodium Channel: easy to open (Low)

```Gen
container: VGSC-SOMA-L

  tub_local:
    RefractoryL ( full: 60x, active: 30x, empty: 0x )

  tub_intricated:
    Na ( contained_in: SOMA)

  context_intricated:
    VDBLowCtx ( contained_by: SOMA ) 
```

### sec: VGSC-SOMA-L

#### VGSC-L_TPC: contextor

Il check su refractory deve essere fatto ad un RF maggiore della eliminazione di Refractory. Questo perche' e' un era nella qualle avviene l'episodio.

```Gen
VGSC-L_Status: ( active: 60x )
  type: contextor
  contained_by: VGSC-SOMA-L

  in_context: VDBLowCtx OR VDBMediumCtx OR VDBMaxCtx
    condition: ( RefractoryH emptiness ) 
      out_context: NaEnterL_ctx
```

#### NaEnterL: accumulator

Se metto il controllo sulla (NOT Ready fullness) il VGSC puo' far entrare un numero di Na non superiore ad un massimo.
Questo sopra è il commmento della versione precedente, ora la quantità di NA increase dipende dal rf di VGSC-H_TPC dato che li c'è la condition sulla presenza delle traccie di refractory

```Gen
NaEnterL: ( active: 1x )
  type: accumulator
  contained_by: VGSC-SOMA-L

  in_context: NaEnterL_ctx
    hypothesis: ( NOT Na full )
      action: [ Na increase]
      trace: None

    hypothesis: ( NOT RefractoryL full )
      action: [ RefractoryL increase ]
      trace: None
```

#### RefractoryLSpill: accumulator

Lo Spill deve avere un rf maggiore dell'interacting che incrementa RefractoryH (interactor precedente)

```Gen
RefractoryLSpill: ( active: 1x )
  type: accumulator
  contained_by: VGSC-L-SOMA

  in_context: any
    hypothesis: NOT ( RefractoryL empty )  
      action: [ RefractoryL decrease ]
      trace: None
```


#### VGSC-SOMA-TUN: Tuner

```Gen
tuner: VGSC-SOMA-TUN

 contained_by: SOMA

 tunes: SOMA/expansion/VGSC-SOMA

 context_intricated:
  - TunPossible ( contained_by: DAY-N )

 tub_local:

 tub_intricated:
```

##### Check: check_tpc

```Gen
context: check_tpc
  contained_by: VGSC-SOMA-TUN

  rf: ( active: 60x )
  in_context: TunPossible

  condition:  
    out_context: TunSomaVcgg
```

##### ?: interacting

```Gen
interacting: ?
  contained_by: TUN-PRE-VGCC

  rf: ( active: x )
  context: TunSomaVcgg

 hypothesis:  
  action: 
  trace: 
```