organism/neuron

README.md

Qui mettiamo la descrizione del neurone.

Da far capire le integrazioni spaziali e temporali, l'allostati, il metabolismo, la modulazione.

Infatti l'espressione G. non e' come un programma tradizionale che puo' essere letto e capito, essendo i comportamenti omomorfi rispetto al codice. In un'espressione G. i comportamenti sono locali in tempo e spazio (contestualizzazione). Non essendoci un flusso programmatico, il commento ai comportamenti locali, non e' sufficienti a spiegare i comportamenti che sara' possibile verificare in diversi ambiti. C'e' quindi bisogno di esprimere i flussi e le chiusure che in diversi ambiti abbiamo voluto esprimere, tramite espressioni locali.

Flussi e chiusure

Flusso da POST a SOMA

• Gli NT che arrivano a BEH-POST-AMPA aprono i AMPA che fa entrare Na che vengono integrati nella POST

• Gli Na nella POST aprono NDMA che fanno entrare Ca2+

• Ca2+ genera VPost nel DB

• L'integrazione di VPost nel DB genera VDB nel SOMA

• L'integrazione di VDB nel SOMA determina AP

• Si aprono i Canali ionici del SOMA, si genera VSOMA e refractory period (emergente)

Flusso da SOMA a POST

bAP

Flusso da SOMA a PRE

AP

Based on the computational model provided, here is the complete breakdown of all simulated behaviors, categorized by functional compartment.

1. Presynaptic Behaviors

• Action Potential Arrival (V_pre): When a spike occurs, the membrane potential (V_pre_state) jumps to a peak and decays based on tau_V_pre. This profile determines the duration of ion channel opening.
• Calcium Influx (VGCC): Voltage-Gated Calcium Channels open based on V_pre_state. The flow is regulated by three "brakes": eCB (retrograde), CDI (inactivation), and mGluR (autoreceptor).
• Intracellular Buffering: Free calcium (Ca_micro) is immediately captured by buffers (B_free). As activity increases and buffers saturate, the effective calcium concentration rises faster (Metabolic Cascade 4).
• Vesicle Release (NT): Neurotransmitter release is deterministic and follows a Hill equation (simulating Synaptotagmin-1 cooperativity). It is limited by the number of vesicles in the Prontly Releasable Pool (N_RRP) and suppressed by high existing levels of NT in the cleft.
• Vesicle Recycling: Vesicles move from the Reserve Pool (N_RP) to the N_RRP at a rate determined by the calcium trace (Tr_Ca). Fast recruitment occurs during high activity; slow recruitment occurs at rest.
• Calcium-Dependent Inactivation (CDI): Local calcium entering through channels causes them to close (CDI_factor). If calcium clearance fails due to low ATP, the CDI "locks" the synapse into a silent state to prevent damage.

2. Postsynaptic Behaviors

• AMPA Activation: Released NT opens AMPA receptors, allowing Na+ influx. This generates the local excitatory post-synaptic potential (EPSP).
• Receptor Desensitization: Continuous exposure to NT reduces the sensitivity of the receptors (Desensitization_level), mimicking the presynaptic CDI behavior to prevent over-stimulation.
• NMDA Coincidence Detection: NMDA channels open only if NT is present AND the membrane is depolarized (removing the Mg2+ block). Depolarization is achieved via local AMPA drive plus the back-propagating action potential (bAP) from the soma.
• eCB Synthesis: When postsynaptic calcium (Ca_post) crosses a specific threshold, Endocannabinoids are synthesized and sent back to the presynapse to suppress further NT release.

3. Dendritic Behaviors

• EPSP Summation: The dendritic branch (DB) acts as a passive integrator. It collects receptor_conductance from all active spines and sums them into V_dend.
• Passive Decay: V_dend decays over time according to tau_dend, determining the temporal window in which multiple inputs can summate to trigger a somatic spike.
• bAP Distribution: When the soma fires, a back-propagating Action Potential (V_bAP) is broadcasted instantly through the dendrite to all spines to enable NMDA coincidence detection.

4. Somatic Behaviors

• Leaky Integration: The soma integrates the signal from the dendrite (V_dend) scaled by soma_weight. It acts as a leaky integrator with a time constant of tau_soma.
• Action Potential (AP) Generation: If V_soma crosses the threshold, a multi-phase AP is triggered:
  1. Rising Phase: Simulated Na+ channel opening (reaches V_AP_peak).
  2. Falling Phase: Simulated K+ channel opening (drops to V_AHP).
  3. AHP Phase: Recovery from hyperpolarization back to rest.
• Refractory Periods: After firing, the soma enters an Absolute Refractory Period (cannot fire) followed by a Relative Refractory Period (threshold is temporarily much higher).

5. Astrocytic Behaviors

• Neurotransmitter Clearance: The astrocyte actively removes NT from the synaptic cleft, governed by the tau_NT_decay and metabolic cycles.
• Glutamine Shuttle: Cleared NT is converted and recycled back to the presynaptic Reserve Pool (RP) with a specific conversion_efficiency.
• IP3 Signaling & Calcium Wave: Accumulated NT triggers IP3 production in the astrocyte. If it crosses a threshold, an astrocytic calcium wave is triggered.
• Metabolic Support: The calcium wave provides a "boost" to the conversion_efficiency, helping the synapse recover vesicles faster during high demand.

6. Metabolic & Shared Behaviors (ATP Loop)

• ATP Consumption: Every Action Potential (Pre and Post) and every calcium pumping action (PMCA, SERCA) drains a shared Glucose/ATP budget.
• Pump Scaling: The speed of ion pumps is determined by a Hill function of available ATP_level. Low energy leads to Pump Failure.
• Metabolic Silencing: A 6-stage cascade where high firing leads to ATP depletion, which causes pump failure, leading to residual calcium, which triggers CDI, finally silencing the synapse to protect against excitotoxicity.

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Logic Summary Table

Input	Process	Output
NT in Cleft	AMPA / NMDA Opening	V_post (Postsynaptic Potential)
V_post	Dendritic Summation	V_dend (Dendritic Potential)
V_dend	Somatic Integration	V_soma (Somatic Potential)
V_soma > Threshold	Spike Kinetics	Forward AP & Retrograde bAP
Low ATP	Pump Failure	Synaptic Silencing (Protection)