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# DEV-N: Modulator
Neuron Development - LTP-LTD Behavior:
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.
- For Presynaptic Strengthening (e.g., un LTP):
- 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.
- 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.
- Neurotrophins (BDNF): Released from the postsynapse in an activity-dependent manner. Presynaptic TrkB receptors activate pathways (PI3K, MAPK) that enhance vesicle docking and Pr.
- For Presynaptic Weakening (e.g., LTD):
- 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.
- Other Lipid Mediators (like LPA) can also act as retrograde signals for depression.
Augmentation:
- Calcium-sensing proteins (Munc13) alter release probability (1-10s range). How?
Upregulation:
- NO/BDNF activates cascades that increase P_r, promote synaptic growth (facilitates LTP). How?
- VGCC TUN
- Potassium channel modulation ??
Downregulation:
- eCBs bind CB1 receptors, inhibit VGCCs, activate K⁺ channels → profound decrease in P_r (DSE/DSI - depolarization-induced suppression)
- CB1 receptor activation (by eCBs)
- Retrograde BDNF (brain-derived neurotrophic factor)
> Night Time Scale
```Gen
modulator: DEV-N
contained_by: N
```
## DEV-RF: Modulator
Perche mettiamo RF in DEV e non in TUN?
```Gen
modulator: DEV-RF
contained_by: DEV-N
```
### DEV-PRE-VesciclesRecycling-RF: Modulator
```Gen
modulator: DEV-PRE-VesciclesRecycling-RF
contained_by: DEV-RF
modulates: BEH-PRE/episode/VesciclesRecycling
# each BEH-PRE is modulated!
tub_dev:
- fulMod ( fullness: None, active: rf/fullness, emptiness: 0x )
- actMod ( fullness: None, active: rf/active, emptiness: 0x )
# qui stiamo modulando l'active di RF mantenendolo fra fullness e
# emptiness dichiarato in VesciclesRecycling
tub_local:
tub_intricated:
- Nox ( contained_by: BEH-POST )
- Ecb ( contained_by: BEH-POST )
```
#### Context
#### Episode
### DEV-PRE-VesiclesFillingRP-RF: Modulator
```Gen
modulator: DEV-PRE-VesiclesFillingRP-RF
contained_by: DEV-RF
modulates:
tub_local:
tub_intricated:
- Nox ( contained_by: BEH-POST )
- Ecb ( contained_by: BEH-POST )
```
#### Context
#### Episode
### DEV-PRE-LactateAtp-RF: Modulator
```Gen
modulator: DEV-PRE-LactateAtp-RF
contained_by: DEV-RF
modulates:
tub_local:
tub_intricated:
- Nox ( contained_by: BEH-POST )
- Ecb ( contained_by: BEH-POST )
```
#### Context
#### Episode
## DEV-TUB-FLOOR: Modulator
Perche mettiamo Full in DEV e non in TUN?
```Gen
modulator: DEV-TUB-FLOOR
contained_by: DEV-N
```
### DEV-PRE-CA2+-TUB: Modulator
```Gen
modulator: DEV-PRE-CA2+-TUB
contained_by: DEV-TUB-FLOOR
modulates: BEH-PRE/tub/Ca2+ # this is the tub whose "full" must be modulated
tub_dev:
- fullMod ( fullness: 100x, active: Ca2+/fullness, emptiness: 50x ) # Ca2+Full "contains" a number of blocks equal to the current Full.
# qui stiamo modulando la fullness di Ca2+, associandola ad
# active di fullMod. Cambiando active di fullMod,
# si cambia la fullness di Ca2+
tub_local:
tub_intricated:
- Nox ( contained_by: BEH-POST )
- Ecb ( contained_by: BEH-POST )
```
#### Context
***Tens Milliseconds Time Scale***
```Gen
context: CheckPreTubCa2+
contained_by: DEV-PRE-FULL-CA2+
in_context: Fixed
rf: 60x
condition: ( empty )
out_context: DecreaseFull
condition: NOT ( empty ) AND NOT ( Ca2+ full )
out_context: Nothing
condition: ( full)
out_context: IncreaseFull
```
#### Episode
```Gen
episode: VgccOpen
contained_by: DEV-PRE-FULL-CA2+
in_context: DecreaseFull
rf: 1x
hypothesis: NOT ( full ) AND NOT ( empty )
action: [ increase, decrease]
trace: None
```
### DEV-PRE-RRP-TUB: Modulator
```Gen
modulator: DEV-PRE-RRP-TUB
contained_by: DEV-TUB-FLOOR
modulates: BEH-PRE/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: BEH-POST )
- Ecb ( contained_by: BEH-POST )
```
#### Context
#### Episode
## DEV-TUB-CONCEPTUAL: Modulator
Qui la PRE e la POST si predispongono per dare le condizioni a SYN di stabilire o eliminare una sinapsi. Per ora questo comportamento lo mettiamo in TUN perche non si tratta di creare o distruggere PRE o POST, ma di rendere disponibile a SYN la possibilita di creare o distruggere una SYN. Durante il Day ce il TUN che mette a disposizione, durante il Night SYN crea o distrugge gli accoppiamenti PRE POST.
ATTENZIONE: Questo e POST e da cambiare, perche ce il passaggio da TubPoss a TubPossSyn a TubAct. E la SYN che passa in TubAct.
> Minutes/hours Time Scale
```Gen
modulator: DEV-TUB-CONCEPTUAL
contained_by: DEV-N
```
### DEV-AXO-BEH-PRE-TUB: Modulator
Qui stiamo ragionanando sulla trasformazione fra bottone presinaptico inattivo e bottone attivo, pronto a diventare parte di una sinapsi. Il ragionamento e' locale, e mette a disposizione o toglie un bottone attivo che un altro ragionamento, in TUN-WTA, fara' su questo bottone, il bottone postisinaptico e una sinapsi disponibile. Agiamo sulla fullness di BEH-PRE.
```Gen
modulator: DEV-AXO-BEH-PRE-TUB
contained_by: DEV-TUB-CONCEPTUAL
modulates: N/AXO/BEH-AXO/expansion/BEH-PRE
# qui stiamo modulando fullness del tub BEH-PRE associandoli a tub_modulation prePos e PreAct.
tub_modulation:
- fulMod ( fullness: 100x, active: BEH-PRE/fullness, empty: 0x ) # aumento di possible di BEH-PRE
- actMod ( fullness: None, active: BEH-PRE/active, empty: BEH-PRE/emptiness ) # riferimento a active di BEH-PRE
context_intricated:
- TunPossible ( contained_by: TUN-N )
tub_local:
tub_intricated:
```
#### Context
```Gen
context: CheckTunSynAxoPrePossibility
contained_by: TUN-SYN-AXO-PRE
in_context: TunPossible
rf: ( active: 60x )
condition:
out_context:
```
#### Episode
```Gen
episode: TunSynAxoPre
contained_by: TUN-SYN-AXO-PRE
in_context: ??
rf: 1x
hypothesis: NOT () AND NOT ()
action: [ increase, decrease]
trace: None
```
### DEV-BD-BEH-POST-TUB: Modulator
```Gen
modulator: DEV-BD-BEH-POST-TUB
contained_by: DEV-TUB-CONCEPTUAL
...
```
#### Context
#### Episode