creato pre_vgcc.md
This commit is contained in:
@@ -1,150 +0,0 @@
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# neuron-dev.md
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Neuron Development - LTP-LTD Behavior:
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This is critical for long-term presynaptic changes. The postsynaptic cell, upon detecting specific activity patterns (like those for LTP/LTD), releases chemical signals that travel backwards to the presynaptic terminal, instructing it to change.
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- For Presynaptic Strengthening (e.g., un LTP):
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- Nitric Oxide (NO): A gas that diffuses freely. During postsynaptic LTP induction (strong NMDAR activation), neuronal NO synthase (nNOS) is activated. NO diffuses into the presynaptic terminal and activates soluble guanylyl cyclase (sGC), raising cGMP levels. This enhances vesicle release via PKG, contributing to presynaptic LTP.
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- Endocannabinoid-Mediated LTP (eLTP): In some synapses, a postsynaptic depolarization triggers production of endocannabinoids (e.g., 2-AG). These bind to presynaptic CB1 receptors, but surprisingly, can initiate a signaling cascade (involving cAMP/PKA) that increases Pr for a long period.
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- Neurotrophins (BDNF): Released from the postsynapse in an activity-dependent manner. Presynaptic TrkB receptors activate pathways (PI3K, MAPK) that enhance vesicle docking and Pr.
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- For Presynaptic Weakening (e.g., LTD):
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- Classical Endocannabinoid-Mediated LTD (eCB-LTD): More common. Moderate postsynaptic activity (mGluR activation or moderate Ca²⁺ rise) triggers 2-AG release. 2-AG binds presynaptic CB1 receptors, which inhibit VGCCs and directly inhibit the release machinery via Gi/o protein signaling, reducing Pr for a long time.
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- Other Lipid Mediators (like LPA) can also act as retrograde signals for depression.
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Augmentation:
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- Calcium-sensing proteins (Munc13) alter release probability (1-10s range). How?
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Upregulation:
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- NO/BDNF activates cascades that increase P_r, promote synaptic growth (facilitates LTP). How?
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- VGCC TUN
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- Potassium channel modulation ??
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Downregulation:
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- eCBs bind CB1 receptors, inhibit VGCCs, activate K⁺ channels → profound decrease in P_r (DSE/DSI - depolarization-induced suppression)
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- CB1 receptor activation (by eCBs)
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- Retrograde BDNF (brain-derived neurotrophic factor)
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```Gen
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NEURON-DEV
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type: developer # ??? (container)
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contained_by: NEURON
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```
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## CA2-PRESYNAPSE-DEV: Developer
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```Gen
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CA2-PRESYNAPSE-DEV
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type: developer
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contained_by: NEURON-DEV
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develops: NEURON/NEURON-BEH/AXON/PRESYNAPSE/tub/Ca2+
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# this is the tub whose "full" must be modulated
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tub_dev: fullMod ( fullness: 100x, active: Ca2+/full, emptiness: 50x )
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# qui stiamo modulando il full di Ca2+, associandolo ad
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# active di fullMod. Cambiando active di fullMod,
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# si cambia la full di Ca2+
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tub_local:
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tub_intricated:
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- Nox ( contained_by: NEURON/NEURON-DAY/AXON/PRESYNAPSE )
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- Ecb ( contained_by: NEURON/NEURON-DAY/AXON/PRESYNAPSE )
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```
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### CheckPreCa2: Contextor
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***Tens Milliseconds Time Scale***
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```Gen
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CheckPreCa2: ( active: 60x )
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type: contextor
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contained_by: NEURON-DEV
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in_context: Fixed
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condition: ( empty )
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out_context: DecreaseCa2Full_ctx
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condition: NOT ( empty ) AND NOT ( Ca2+ full ) ???
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out_context: Nothing_ctx
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condition: ( full)
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out_context: IncreaseFull_ctx
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```
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### DecreasePreCa2Full: Accumulator
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```Gen
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DecreasePreCa2Full: ( active: 1x )
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type: accumulator
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contained_by: NEURON-DEV
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in_context: DecreaseCa2Full_ctx
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hypothesis: NOT ( full ) AND NOT ( empty )
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action: [ increase, decrease]
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trace: None
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```
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### IncreasePreCa2Full: Accumulator
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```Gen
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IncreasePreCa2Full: ( active: 1x )
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type: accumulator
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contained_by: NEURON-DEV
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in_context: IncreaseCa2Full_ctx
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hypothesis: NOT ( full ) AND NOT ( empty )
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action: [ increase, decrease]
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trace: None
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```
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## RRP-PRESYNAPSE-DEV: Developer
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```Gen
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RRP-PRESYNAPSE-DEV
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type: developer
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contained_by: NEURON-DEV
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develops: NEURON/NEURON-BEH/AXO/PRESYNAPSE/tub/Rrp
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# this is the tub whose "full" must be modulated
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tub_dev: fullMod ( fullness: 100x, active: Rrp/fullness, emptiness: 50x )
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# RrpFull "contains" a number of blocks equal to the current Full.
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# qui stiamo modulando la fullness di Rrp, associandola ad
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# active di fullMod. Cambiando active di fullMod,
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# si cambia la fullness di Rrp
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tub_local:
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tub_intricated:
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- Nox ( contained_by: NEURON/NEURON-BEH/DENDRITIC-BRANCH/POSTSYNAPSE )
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- Ecb ( contained_by: NEURON/NEURON-BEH/DENDRITIC-BRANCH/POSTSYNAPSE )
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```
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### Contextor
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### Accumulator
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## PRESYNAPSE-AXO-DEV: Developer
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Qui stiamo ragionanando sull'aggiunta o eliminazione di bottoni presynaptici. Il TUN della PRESYNAPSE e' fatto in WINNERTAKEALL/EXCITATION.
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## POSTSYNAPSE-DENDRITIC-BRANCH-DEV: Developer
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Qui stiamo ragionanando sull'aggiunta o eliminazione di bottoni postsynaptici. Il TUN della POSTSYNAPSE e' fatto in WINNERTAKEALL/EXCITATION.
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+104
-142
@@ -4,24 +4,24 @@ include_toc: true
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# presynapse.md
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- qui comprendiamo:
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- [PRESYNAPSE](#presynapse)
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- [VCGG](#vgcc_pre) Voltage-Controlled Gated Channels
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- qui comprendiamo: PRESYNASPE
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## PRESYNAPSE
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- modulation:
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- is expanded and developed by: [AXON](axon.md)
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- is tuned by: ORGANISM, organs, modules
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- expands and tunes: [VGCC_PRE](#vgcc_pre)
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- expands and tunes: [PRE_VGG](pre_vgcc)
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```Gen
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PRESYNAPSE
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type: comprehension
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include: pre_vgcc.md
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expansion:
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_@Vgcc_pre: TUB [ comprehension: VGCC_PRE, full: 10x, active: 5x, empty: 2x ]
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_@pre_vgcc: TUB [ comprehension: PRE_VGCC, full: 10x, active: 5x, empty: 2x ]
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# il tub serve al tuning
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intrication:
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@@ -58,11 +58,11 @@ PRESYNAPSE
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# Behaviour
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$: BEHAVIOUR [ behaviour: MAIN_PRE ]
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$: BEHAVIOUR [ behaviour: TUNE_VGCC_PRE ]
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$: BEHAVIOUR [ behaviour: DEV-TUBS_PRE ] # da eliminare neuron-dev
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$: BEHAVIOUR [ behaviour: TUNE_PRE_VGCC ]
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$: BEHAVIOUR [ behaviour: DEV-TUBS_PRE ]
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```
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### MAIN_PRE
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### MAIN_PRE: !DAY
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```Gen
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MAIN_PRE
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@@ -343,13 +343,13 @@ Ca2TracesClearance
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trace: None
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```
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### TUNE_VGCC_PRE
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### TUNE_PRE_VGCC: DAY!
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```Gen
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TUNE_VGCC_PRE
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TUNE_PRE_VGCC
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type: behaviour
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# qui stiamo aggiungendo o eliminando VGCC_PRE. Fra un massimo full e minimo empty (empty puo' non essere 0)
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# qui stiamo aggiungendo o eliminando PRE_VGCC. Fra un massimo full e minimo empty (empty puo' non essere 0)
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# contained_by: PRESYNAPSE non e' contenuto, si attacca.
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activity_scope: !DAY
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@@ -385,9 +385,9 @@ CheckVgccPreTun
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out_context: *TryTunDownPreVcgg
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```
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#### *TryTunUpPreVcgg
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##### *TryTunUpPreVcgg
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##### PossibleUpPreVgccTun
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###### PossibleUpPreVgccTun
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```Gen
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PossibleUpPreVgccTun
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@@ -400,9 +400,9 @@ PossibleUpPreVgccTun
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trace:
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```
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#### *TryTunDownPreVcgg
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##### *TryTunDownPreVcgg
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##### PossibleDownPreVgccTun: ( active: 10x ) accumulator
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###### PossibleDownPreVgccTun: ( active: 10x ) accumulator
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```Gen
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PossibleDownPreVgccTun
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@@ -415,159 +415,121 @@ PossibleDownPreVgccTun
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trace:
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```
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## VGCC_PRE
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Modulation:
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- is tuned by: [PRESYNAPSE](#presynapse)
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Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.
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### DEV_TUBS_PRE: !NIGHT
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```Gen
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VGCC-PRE
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type: comprehension
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expansion:
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intrication:
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# Scope
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!DAY: INTRICATION [ ref: &ORGANISM.!DAY ]
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!NIGHT: INTRICATION [ ref: &ORGANISM.!NIGHT ]
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# Context
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*AP: INTRICATION [ ref: &SOMA.*AP ]
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# Tub
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_NT: INTRICATION [ ref: &ASTROSYNAPSE._NT ]
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_Ca2: INTRICATION [ ref: &PRESYNAPSE._Ca2 ]
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instantiation:
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# Behaviour
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@: BEHAVIOUR [ behaviour: VGCC_PRE_BEH ]
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```
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### BEHAVIOR_VGCC_PRE
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Voltage-Controlled Gated Channels: Qui per ora non gestiamo l'evoluzione della depolarizzazione. Alla scomparsa dell'AP, i VGCC smettono di funzionare.
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```Gen
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VGCC_PRE_BEH
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DEV_TUBS_PRE
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type: behaviour
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within_scope: !DAY
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activity_scope: !NIGHT
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snippet:
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# *TunePossible
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@: CONTEXTOR [ snippet: CheckVgccPreTun, rf: active 60x ]
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# *TryTunUpPreVcgg
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@: ACCUMULATOR [ snippet: PossibleUpPreVgccTun, rf:active 10x ]
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# *TryTunDownPreVcgg
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@: ACCUMULATOR [ snippet: PossibleDownPreVgccTun, rf:active 10x ]
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```
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#### CA2-PRESYNAPSE-DEV: Developer
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```Gen
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CA2-PRESYNAPSE-DEV
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type: behaviour
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snippets:
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# *AP
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@: ACCUMULATOR [ snippet: Ca2enterLow, rf: active 12x ]
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@: ACCUMULATOR [ snippet: Ca2enterMedium, rf: active 6x ]
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@: ACCUMULATOR [ snippet: Ca2enterHigh, rf: active 3x ]
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develops: NEURON/NEURON-BEH/AXON/PRESYNAPSE/tub/Ca2+
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# this is the tub whose "full" must be modulated
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# NOT *AP
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@: ACCUMULATOR [ snippet: Ca2ClearanceLow, rf: active 24x ]
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@: ACCUMULATOR [ snippet: Ca2ClearanceHigh, rf: active 4x ]
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tub_dev: fullMod ( fullness: 100x, active: Ca2+/full, emptiness: 50x )
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# qui stiamo modulando il full di Ca2+, associandolo ad
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# active di fullMod. Cambiando active di fullMod,
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# si cambia la full di Ca2+
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tub_local:
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tub_intricated:
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- Nox ( contained_by: NEURON/NEURON-DAY/AXON/PRESYNAPSE )
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- Ecb ( contained_by: NEURON/NEURON-DAY/AXON/PRESYNAPSE )
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```
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#### *AP
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#### CheckPreCa2: Contextor
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Da rivedere le condizioni per aggiungere mGluR che ha come proxy NT concentration!!!!!
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Here we comprehend the breaking activity on VGCC by: CDI, eCB and mGluR:
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Qui semplifichiamo:
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- Approssimiamo CDI con concentrazione di Ca2.
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\-- CDI is calcium-dependent inactivation of VGCCs. The inactivation happens because Ca2 enters through the channel and binds to a calmodulin tethered to the channel's intracellular face, physically blocking it from reopening. This is a local, channel-specific event — it requires Ca2 to be flowing through that channel right now, not residual Ca2 drifting in the cytosol between spikes.
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\-- The recovery, by contrast, should run every millisecond unconditionally — CDI de-inactivation is a continuous process that proceeds whenever Ca2 dissociates from calmodulin, which depends on the ambient Ca_micro level at all times.
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- Approssimiamo mGluR con concentrazione NT
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- **Open** — zero active brakes. mGluR alone never escapes this group because its ceiling is alpha_mGluR = 0.4, meaning even at full it only removes 40% of conductance, leaving 60% — still above the 85% threshold. So mGluR is irrelevant to the open/not-open boundary. Only CDI and eCB decide.
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- **Reduced/partial** — exactly one meaningful brake active. Either CDI has started building (mediumness), or eCB has risen from sustained postsynaptic activity, but not both simultaneously. The system is aware something is happening but has not compounded yet. This is the normal operating range during moderate sustained firing.
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- **Suppressed** — two brakes multiplying. The compounding is what defines this zone — no single variable alone produces it (except CDI approaching full). 0.5 × 0.5 = 0.25 remaining is where the synapse starts losing significant transmission efficacy. Biologically this is the pre-silence warning zone: CDI is building from residual Ca2 while eCB is already engaged from postsynaptic activity.
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- **Closed — CDI** = full is the only reliable hard rule. Because CDI can reach 1.0 and appears as (1 - CDI_factor) in the formula, it alone drives conductance to zero regardless of eCB and mGluR state. The three-brake overlap corner case (eCB=full + CDI=mediumness + mGluR=full) also reaches here, but in practice CDI reaching full is the primary biological mechanism.
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Devo controllare che le condizioni sotto siano esaustive. Qui ho confuso high con low, e inoltre ho messo NT per mGluR che devo controllare che abbia senso.
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##### Ca2enterLow
|
||||
***Tens Milliseconds Time Scale***
|
||||
|
||||
```Gen
|
||||
Ca2enterLow
|
||||
type: accumulator
|
||||
CheckPreCa2: ( active: 60x )
|
||||
|
||||
in_context: *AP
|
||||
type: contextor
|
||||
contained_by: NEURON-DEV
|
||||
|
||||
hypothesis: _Ca2 empty AND _eCB empty
|
||||
action: [ _Ca2 increase, _ATP decrease ]
|
||||
in_context: Fixed
|
||||
|
||||
condition: ( empty )
|
||||
out_context: DecreaseCa2Full_ctx
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||||
|
||||
condition: NOT ( empty ) AND NOT ( Ca2+ full ) ???
|
||||
out_context: Nothing_ctx
|
||||
|
||||
condition: ( full)
|
||||
out_context: IncreaseFull_ctx
|
||||
```
|
||||
|
||||
#### DecreasePreCa2Full: Accumulator
|
||||
|
||||
```Gen
|
||||
DecreasePreCa2Full: ( active: 1x )
|
||||
|
||||
type: accumulator
|
||||
contained_by: NEURON-DEV
|
||||
|
||||
in_context: DecreaseCa2Full_ctx
|
||||
|
||||
hypothesis: NOT ( full ) AND NOT ( empty )
|
||||
action: [ increase, decrease]
|
||||
trace: None
|
||||
```
|
||||
|
||||
##### Ca2enterMedium
|
||||
#### IncreasePreCa2Full: Accumulator
|
||||
|
||||
```Gen
|
||||
Ca2enterMedium
|
||||
type: accumulator
|
||||
IncreasePreCa2Full: ( active: 1x )
|
||||
|
||||
in_context: *AP
|
||||
type: accumulator
|
||||
contained_by: NEURON-DEV
|
||||
|
||||
hypothesis: _Ca2 mediumness OR
|
||||
( _eCB mediumness AND _Ca2 empty ) OR
|
||||
( _eCB full AND _Ca2 empty AND _NT empty )
|
||||
action: [ _Ca2 increase, _ATP decrease ]
|
||||
in_context: IncreaseCa2Full_ctx
|
||||
|
||||
hypothesis: NOT ( full ) AND NOT ( empty )
|
||||
action: [ increase, decrease]
|
||||
trace: None
|
||||
```
|
||||
|
||||
##### Ca2enterHigh
|
||||
#### RRP-PRESYNAPSE-DEV: Developer
|
||||
|
||||
```Gen
|
||||
Ca2enterHigh
|
||||
type: accumulator
|
||||
RRP-PRESYNAPSE-DEV
|
||||
|
||||
in_context: *AP
|
||||
type: developer
|
||||
contained_by: NEURON-DEV
|
||||
|
||||
hypothesis: ( _Ca2 mediumness AND _eCB full ) OR
|
||||
_eCB mediumness
|
||||
action: [ _Ca2 increase, _ATP decrease ]
|
||||
trace: None
|
||||
```
|
||||
|
||||
#### NOT *AP
|
||||
|
||||
Qui eliminiamo Ca2. Il tempo che ci mette ad eliminare il Ca2 dovrebbe essere minoe dell'inervallo fra un *AP e un'altra. Siccome non comprendiamo per ora \_ATP, non c'e' accumulo di Ca2 per mancanza di \_ATP (stanchezza).
|
||||
|
||||
Non non comprendiamo anche il ristabilimento del Voltage, con altri Ioni entranti e uscenti, per ora tutto dipende da AP del SOMA. Non comprendiamo per ora:
|
||||
|
||||
- PMCA: primary, ATP-dependent
|
||||
- NCX: fast, NOT ATP-dependent
|
||||
- SERCA: slowest, ATP-dependent
|
||||
|
||||
Qui disinguiamo:
|
||||
|
||||
- Ca+2 fullness che si puo' verificare alla fine di un AP
|
||||
- NOT Ca2 fullness che svuota piu' lentamente
|
||||
- da capire se serve veramente questa distinzione per il tempo di svuotamento.
|
||||
|
||||
##### Ca2ClearanceLow
|
||||
|
||||
```Gen
|
||||
Ca2ClearanceLow
|
||||
type: accumulator
|
||||
|
||||
in_context: NOT *AP
|
||||
|
||||
hypothesis: NOT _Ca2 fullness AND NOT _Ca2 empty
|
||||
action: [ _Ca2 decrease ]
|
||||
trace: None
|
||||
```
|
||||
|
||||
##### Ca2ClearanceHigh
|
||||
|
||||
```Gen
|
||||
Ca2ClearanceHigh
|
||||
type: accumulator
|
||||
|
||||
in_context: NOT *AP
|
||||
|
||||
hypothesis: NOT _Ca2 empty
|
||||
action: [Ca2 decrease]
|
||||
trace: None
|
||||
develops: NEURON/NEURON-BEH/AXO/PRESYNAPSE/tub/Rrp
|
||||
# this is the tub whose "full" must be modulated
|
||||
|
||||
tub_dev: fullMod ( fullness: 100x, active: Rrp/fullness, emptiness: 50x )
|
||||
# RrpFull "contains" a number of blocks equal to the current Full.
|
||||
# qui stiamo modulando la fullness di Rrp, associandola ad
|
||||
# active di fullMod. Cambiando active di fullMod,
|
||||
# si cambia la fullness di Rrp
|
||||
|
||||
tub_local:
|
||||
|
||||
tub_intricated:
|
||||
- Nox ( contained_by: NEURON/NEURON-BEH/DENDRITIC-BRANCH/POSTSYNAPSE )
|
||||
- Ecb ( contained_by: NEURON/NEURON-BEH/DENDRITIC-BRANCH/POSTSYNAPSE )
|
||||
```
|
||||
|
||||
Reference in New Issue
Block a user