# postsynapse.md Qui comprendiamo: - POSTSYNAPSE: Postsynapse - POST-AMPA: AMPA receptors (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors) ## POSTSYNAPSE: Container **Simplified Behaviors**: — ms: - NT arrives in cleft → AMPA receptors bind NT (receptor availability constant, no desensitization) - V_post rises with AMPA conductance, decays passively each ms - bAP arrives → V_post receives additional depolarisation boost - NMDA gate checks coincidence: NT_cleft AND V_post both non-zero - Mg_block_removal = V_post / (V_post + V_NMDA_half) — sigmoid of V_post - Ca²⁺ enters spine via NMDA: Ca_post += k_NMDA × NT_cleft × Mg_block_removal - Ca_post decays slowly each ms (single exponential, no pump detail) - Ca_post_history updated every ms (feeds seconds loop) - V_post_history updated every ms (retained for reference) — seconds: - Ca_post_history mean computed over past 2 s - eCB synthesised when Ca_post_history mean exceeds eCB threshold - eCB_level decays when Ca_post_history mean falls below threshold - eCB_level written → read by presynapse as retrograde brake on VGCCs - Ca_post_history compared to LTP/LTD thresholds → plasticity tag set — mins: - If Plasticity_LTP tagged → AMPA density increases - If Plasticity_LTD tagged → AMPA density decreases - AMPA density feeds back into receptor_conductance ceiling for next cycle --- **G expression**: ```Gen POSTSYNAPSE - bAP_ctx -- Ca Influx CaNDMAEnterMax: interacting CaNDMAEnterMed: interacting - NOT bAP_ctx: -- Ca Influx CaNDMAEnterMedNotBap: interacting CaNDMAEnterLow: interacting -- Ca Clearence CaClearance: interacting -- V Influx VPostMax: interacting VPostMed: interacting VPostLow: interacting -- V Clearence VPostClearance: interacting POST-AMPA - NOT bAP_ctx -- Na Influx NaAMPAEnterMax: interacting NaAMPAEnterMed: interacting POST-NA-CLEAR - NOT bAP_ctx -- Na Clearence NaClearanceHigh: interacting NaClearanceLow: interacting ``` **Tubs:** - **Na**: Ioni entranti tramite AMPA receptors - **NT**: - **Ca2+**: Ioni entranti tramite NMDA - **VPost**: il voltage che viene sentito in DB - **eCB**: - **Nox**:? --- ```Gen container: POSTSYNAPSE expansion: - POST-AMPA ( full: 10x, active: 5x, empty: 2x ) # modulated_by: TUN-POST-IC # possible/actual - POST-NA-CLEAR ( full: 1x, active: 1x, empty: 0x ) # modulated_by: ?? tub_local: - Ca2+ ( full: 60x, active: 30x, empty: 0x ) - Na ( full: 60x, active: 30x, empty: 0x ) - Nox ( full: 100x, active: 20x, empty: 0x ) # Nitric Oxide (NO): A gas that diffuses freely. - eCB ( full: 100x, active: 20x, empty: 0x ) # Endocannabinoids (e.g., 2-AG) tub_intricated: - NT ( contained_by: SYNAPSE ) - VPost ( contained_by: BD ) context_intricated: - bAp ( contained_by: SOMA ) ``` ### ms: behaviors POST ![post-ltp-ltd.png](.attachments/post-ltp-ltd.png) #### CheckNa: Contexting ```Gen context: CheckNa ## DA ELIMINARE ## contained_by: BEH-POST in_context: Fixed rf: ( active: 60x ) condition: (Na fullness) out_context: NaMax condition: (Na mediumness) out_context: NaMedium condition: (Na emptiness) out_context: NaLow ``` ##### CaNDMAEnterMax: Interacting ```Gen interacting: CaNDMAEnterMax contained_by: POSTSYNAPSE in_context: bAp rf: ( active: 2x ) hypothesis: NOT (Ca2+ full) AND (Na fullness OR Na mediumness) action: [Ca2+ increase] trace: ``` ##### CaNDMAEnterMed: Interacting ```Gen interacting: CaNDMAEnterMed contained_by: POSTSYNAPSE in_context: bAp rf: ( active: 4x ) hypothesis: NOT (Ca2+ full) AND (Na emptiness) action: [Ca2+ increase] trace: ``` ##### CaNDMAEnterMedNotBap: Interacting ```Gen interacting: CaNDMAEnterMedNotBap contained_by: POSTSYNAPSE in_context: NOT bAP rf: ( active: 4x ) hypothesis: NOT (Ca2+ full) AND (Na fullness) action: [Ca2+ increase] trace: ``` ##### CaNDMAEnterLow: Interacting ```Gen interacting: CaNDMAEnterLow contained_by: POSTSYNAPSE in_context: NOT bAP rf: ( active: 12x ) hypothesis: NOT (Ca2+ full) AND (Na mediumness) action: [Ca2+ increase] trace: ``` #### CaClearance: Interacting ```Gen interacting: CaClearance contained_by: POSTSYNAPSE in_context: NOT bAP rf: ( active: 24x ) # Low hypothesis: NOT (Ca2+ empty) action: [Ca2+ decrease] trace: None ``` #### CheckCaVPost:Contexting Qui controlliamo il livello di Ca2+, che e' stato fatto entrare da NMDA, e creaiamo VPost nel DB. Abbiamo fatto una semplificazione, perche' il Ca2+ dovrebbe entrare nel DB in base a V_Post che fa aprire canali in DB. Invece creaimo direttamente il VPost. ```Gen context: CheckCaVPost ### DA ELIMINARE ### contained_by: BEH-POST in_context: Fixed rf: ( active: 60x ) condition: (Ca2+ fullness) out_context: CaMax condition: (Ca2+ mediumness) out_context: CaMedium condition: (Ca2+ emptiness) out_context: CaLow ``` ##### VPostMax:Interacting ##### VPostMed:Interacting ##### VPostMin:Interacting ##### VPostClearance:Interacting Il clearance lo facciamo qui nel container dove creaiamo anche i VPost, perche' altrimenti, se lo facessimo in DB, perderemmo l'aspetto temporale della contribuzione dei singoli POST. ## POST-AMPA: Container ```Gen container: POST-AMPA tub_intricated: - NT ( contained_by: SYNAPSE ) context_intricated: - Na ( contained_by: POSTSYNAPSE ) ``` ### ms: behaviors AMPA #### CheckNTPost: Contexting ```Gen context: CheckNTPost ### DA ELIMINARE ### contained_by: POST-AMPA in_context: NOT bAP_ctx rf: ( active: 8x ) condition: (NT mediumness) out_context: NTMedium condition: (NT fullness) out_context: NTFull ``` ##### NaAMPAEnterMax: Interacting ```Gen interacting: NaAMPAEnterMax contained_by: POST-AMPA in_context: NOT bAP_ctx rf: ( active: 2x ) hypothesis: (NT fullness) action: [Na increase] trace: ``` ##### NaAMPAEnterMed: Interacting ```Gen interacting: NaAMPAEnterMed contained_by: POST-AMPA in_context: NOT bAP_ctx rf: ( active: 4x ) hypothesis: (NT mediumness) action: [Na increase] trace: ``` #### TUN-POST-AMPA: Tuner ```Gen tuner: TUN-POST-AMPA contained_by: BEH-POST tunes: BEH-POST/expansion/BEH-POST-IC tub_modulation: # in TUN agiamo su POS/ACT - posMod ( fullness: None, active: BEH-POST-IC/fullness, empty: 0x) # riferimento a possible di BEH-PRE - actMod ( fullness: None, active: BEH-POST-IC/active, empty: BEH-POST-IC/emptiness) # riferimento a active di BEH-PRE context_intricated: - TunPossible ( contained_by: DAY-N ) tub_local: tub_intricated: ``` ##### Contexting ```Gen context: Check contained_by: TUN-POST-AMPA in_context: TunPossible rf: ( active: 60x ) condition: out_context: TunPostIc ``` ##### Interacting ```Gen episode: ? contained_by: TUN-POST-AMPA in_context: TunPostIc rf: ( active: x ) hypothesis: action: trace: ``` ## BEH-POST-NA-CLEAR: Container Il clearance lo mettiamo qui come container, perche' gli AMPA creano, e questo container pompa fuori. Qui non e' un problema di perdere l'integrazione temporale, perche' gli AMPA sono tutti uguali nel loro behavior. Abbiamo messo gli AMPA come container perche' cosi' possiamo modularne la numerosita'. ```Gen container: BEH-POST-NA-CLEAR context_intricated: - Na ( contained_by: BEH-POST ) ``` ### ms: behaviors NA-CLEAR #### NaClearanceHigh: Interacting #### NaClearanceLow: Interacting