# 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: ```