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 ( fullness: 50x, active: 20x, emptiness: 10x ) 
      # modulated_by: VGSC-SOMA-H-TUN # possible/actual

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

    - VGSC-SOMA-L ( fullness: 50x, active: 20x, emptiness: 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: check_tpc

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
check_tpc: SOMA-Status
  contained_by: SOMA

  rf: ( active: 60x )
  in_context: any

  condition: ( VDB fullness ) AND NOT ApCtx
    out_context: VDBMaxCtx

  condition: ( VDB mediumness ) AND NOT ApCtx
    out_context: VDBMediumCtx 

  condition: ( VDB emptiness ) AND NOT ApCtx
    out_context: VDBLowCtx

  condition: NOT ( Na empty )
    out_context: NaSpill_ctx

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

#### SomaSpike: check_tpc

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
check_tpc: SomaSpike
  contained_by: SOMA

  rf: ( active: 30x )
  in_context: any

  condition: ( Na fullness ) AND ( RefractorySoma emptiness )
    out_context: ApCtx
    out_context: bApCtx
```

#### ActiveAP: interacting

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
interacting: ActiveAP
  contained_by: SOMA

  rf: ( active: 8x )
  in_context: ApCtx

  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: interacting

Questo potrebbe non servire se eliminiamo tutti Na durante ActiveAP.

```Gen
interacting: NaSpill
  contained_by: SOMA

  rf: ( active: 8x )
  in_context: NaSpill_ctx

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

#### RefractorySomaSpill: interacting

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

```Gen
interacting: RefractorySomaSpill
  contained_by: SOMA

  rf: ( active: 16x )
  in_context: RefractorySoma_ctx

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

### sec: SOMA

### min: SOMA

#### 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: 
```

## 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)
  
```

### sec: VGSC-SOMA-H

#### VGSC-H_Status: check_tpc

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
check_tpc: VGSC-H_Status

  contained_by: VGSC-SOMA-H

  rf: ( active: 60x )
  in_context: any

  condition: VDBMaxCtx AND ( RefractoryH emptiness ) 
    out_context: NaEnterH_Ctx

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

#### NaEnterH: interacting

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
interacting: NaEnterH
  contained_by: VGSC-H-SOMA

  in_context: NaEnterH_Ctx
  rf: ( active: 1x )

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

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

#### RefractoryHSpill: interacting

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

```Gen
interacting: RefractoryHSpill
  contained_by: VGSC-H-SOMA

  rf: ( active: 1x )
  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)
  
```

### sec: VGSC-SOMA-M

#### VGSC-M_TPC: check_Status

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
check_tpc: VGSC-M_Status
  contained_by: VGSC-SOMA-M

  rf: ( active: 60x )
  in_context: VDBMediumCtx OR VDBMaxCtx

  condition: ( RefractoryH emptiness ) 
    out_context: NaEnterM_Ctx
```

#### NaEnterM: interacting

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
interacting: NaEnterM
  contained_by: VGSC-M-SOMA

  rf: ( active: 1x )
  in_context: NaEnterM_Ctx

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

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

#### RefractoryMSpill: interacting

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

```Gen
interacting: RefractoryMSpill
  contained_by: VGSC-M-SOMA

  rf: ( active: 1x )
  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)
  
```

### sec: VGSC-SOMA-L

#### VGSC-L_TPC: check_Status

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
check_tpc: VGSC-L_Status
  contained_by: VGSC-SOMA-L

  rf: ( active: 60x )
  in_context: VDBLowCtx OR VDBMediumCtx OR VDBMaxCtx

  condition: ( RefractoryH emptiness ) 
    out_context: NaEnterL_Ctx
```

#### NaEnterL: interacting

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
interacting: NaEnterL
  contained_by: VGSC-L-SOMA

  rf: ( active: 1x )
  in_context: NaEnterL_Ctx

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

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

#### RefractoryLSpill: interacting

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

```Gen
interacting: RefractoryLSpill
  contained_by: VGSC-L-SOMA

  rf: ( active: 1x )
  in_context: any

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