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# DEV-N: Modulator
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Neuron Development - LTP-LTD Behavior:
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Il DEV-N lavora durante Night a tempi lunghi rispetto a BEH-N. In pratica cambia la forma delle possibilita’ di BEH-N.
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Il DEV contiene quei behavior di modulazione che cambiano la somma (fullness + active). La modulazione DEV aumenta/diminuisce (fullness + active). Ovvero c’e’ creazione di nuova “forma” di possibilita’.
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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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> Night Time Scale
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```Gen
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modulator: DEV-N
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contained_by: N
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```
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## DEV-RF: Modulator
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Perche’ mettiamo RF in DEV e non in TUN?
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```Gen
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modulator: DEV-RF
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contained_by: DEV-N
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```
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### DEV-PRE-VesciclesRecycling-RF: Modulator
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```Gen
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modulator: DEV-PRE-VesciclesRecycling-RF
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contained_by: DEV-RF
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modulates: BEH-PRE/episode/VesciclesRecycling
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# each BEH-PRE is modulated!
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tub_dev:
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- fulMod ( fullness: None, active: rf/fullness, emptiness: 0x )
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- actMod ( fullness: None, active: rf/active, emptiness: 0x )
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# qui stiamo modulando l'active di RF mantenendolo fra fullness e
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# emptiness dichiarato in VesciclesRecycling
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tub_local:
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tub_intricated:
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- Nox ( contained_by: BEH-POST )
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- Ecb ( contained_by: BEH-POST )
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```
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#### Context
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#### Episode
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### DEV-PRE-VesiclesFillingRP-RF: Modulator
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```Gen
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modulator: DEV-PRE-VesiclesFillingRP-RF
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contained_by: DEV-RF
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modulates:
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tub_local:
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tub_intricated:
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- Nox ( contained_by: BEH-POST )
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- Ecb ( contained_by: BEH-POST )
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```
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#### Context
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#### Episode
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### DEV-PRE-LactateAtp-RF: Modulator
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```Gen
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modulator: DEV-PRE-LactateAtp-RF
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contained_by: DEV-RF
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modulates:
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tub_local:
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tub_intricated:
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- Nox ( contained_by: BEH-POST )
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- Ecb ( contained_by: BEH-POST )
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```
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#### Context
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#### Episode
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## DEV-FULL: Modulator
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Perche’ mettiamo Full in DEV e non in TUN?
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```Gen
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modulator: DEV-FULL
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contained_by: DEV-N
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```
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### DEV-PRE-CA2+-FULL: Modulator
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```Gen
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modulator: DEV-PRE-CA2+-FULL
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contained_by: DEV-FULL
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modulates: BEH-PRE/tub/Ca2+ # this is the tub whose "full" must be modulated
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tub_dev:
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- fullMod ( fullness: 100x, active: Ca2+/fullness, emptiness: 50x ) # Ca2+Full "contains" a number of blocks equal to the current Full.
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# qui stiamo modulando la fullness di Ca2+, associandola ad
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# active di fullMod. Cambiando active di fullMod,
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# si cambia la fullness di Ca2+
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tub_local:
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tub_intricated:
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- Nox ( contained_by: BEH-POST )
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- Ecb ( contained_by: BEH-POST )
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```
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#### Context
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***Tens Milliseconds Time Scale***
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```Gen
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context: CheckPreTubCa2+
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contained_by: DEV-PRE-FULL-CA2+
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in_context: Fixed
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rf: 60x
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condition: ( empty )
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out_context: DecreaseFull
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condition: NOT ( empty ) AND NOT ( Ca2+ full )
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out_context: Nothing
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condition: ( full)
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out_context: IncreaseFull
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```
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#### Episode
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```Gen
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episode: VgccOpen
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contained_by: DEV-PRE-FULL-CA2+
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in_context: DecreaseFull
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rf: 1x
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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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### DEV-PRE-RRP-FULL: Modulator
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```Gen
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modulator: DEV-PRE-RRP-FULL
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contained_by: DEV-FULL
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modulates: BEH-PRE/tub/Rrp # this is the tub whose "full" must be modulated
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tub_dev:
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- fullMod ( fullness: 100x, active: Rrp/fullness, emptiness: 50x ) # 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: BEH-POST )
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- Ecb ( contained_by: BEH-POST )
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```
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#### Context
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#### Episode
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