From 41dac53204e7d0300618ee1d50526f286f3af502 Mon Sep 17 00:00:00 2001 From: ocrampal Date: Thu, 26 Mar 2026 12:56:17 +0100 Subject: [PATCH] commento ASTRO --- astrocyte/AST.md | 28 +++++++++++++++++++++++++++- neuron/BEH-AXO.md | 11 ++++++----- 2 files changed, 33 insertions(+), 6 deletions(-) diff --git a/astrocyte/AST.md b/astrocyte/AST.md index be387c9..7eb36f4 100644 --- a/astrocyte/AST.md +++ b/astrocyte/AST.md @@ -2,7 +2,33 @@ ## AST: Comprehension -**Astrocyte**: Qui comprendiamo Astrocyte, sia BEH che TUN. Per ora non esprimiamo il DEV, partiamo da un numero fisso di fullness SYN, e con TUN moduliamo l'associazione di PRE<->POST tramite is SYN assegnati a ciascun AST. Quando esprimiamo DEV, il ragionamento sara' nell'ambito del network di Astrocytes, tipo se c'e' abbastanza ATP o cose del genere. +Qui comprendiamo Astrocyte, sia BEH che TUN. Per ora non esprimiamo il DEV, partiamo da un numero fisso di fullness SYN, e con TUN moduliamo l'associazione di PRE<->POST tramite is SYN assegnati a ciascun AST. Quando esprimiamo DEV, il ragionamento sara' nell'ambito del network di Astrocytes, tipo se c'e' abbastanza ATP o cose del genere. + +A single astrocyte has a highly branched structure with thousands of fine processes, each wrapping around a different synapse. A human cortical astrocyte can contact anywhere from 100,000 to 2 million synapses simultaneously. So the question of selectivity is real and important. + +**The astrocyte is not globally uniform — it is locally selective**: + +The calcium wave does not behave like a uniform broadcast. It has two distinct modes: + +The first is a **local microdomain response**. When a single synapse fires heavily, the IP3 signal and the resulting calcium elevation can remain confined to the astrocyte process wrapping that specific synapse. The glutamine shuttle boost, the gliotransmitter release, and the EAAT upregulation all happen locally at that process tip — the rest of the astrocyte is unaffected. This is the normal case during moderate activity. + +The second is a **propagating wave**. When activity is sustained and intense enough, the calcium signal spreads from process to process across the astrocyte body and even into neighbouring astrocytes via gap junctions. This is the threshold event that IP3 models. Once the wave propagates, the response is no longer selective — it affects multiple synapses under that astrocyte's territory. + +**What this means for your model**: + +Your current model simulates a single tripartite synapse — one presynapse, one postsynapse, one astrocyte process. In that context the selectivity question does not arise because there is only one synapse to serve. + +But if you ever extend the model to multiple synapses under one astrocyte, the IP3 threshold becomes the selectivity mechanism. Below threshold, each synapse gets a local response proportional to its own activity. Above threshold — when the wave propagates — the astrocyte boosts all synapses in its territory, not just the active one. This is actually a form of network-level coordination: a heavily firing synapse can trigger a boost that benefits its neighbours, which may be important for synchronising activity across a local circuit. + +The simplified model could capture this with a single parameter: + +— selectivity rule: + +- IP3 below threshold → boost applies only to this synapse (local) + +- IP3 above threshold → boost applies to all synapses in territory (broadcast) + +For a single-synapse model the distinction is invisible. But keeping the threshold concept in the model now means the architecture is already correct if you scale up later. ```Gen comprehension: AST diff --git a/neuron/BEH-AXO.md b/neuron/BEH-AXO.md index 9f074da..e207f0c 100644 --- a/neuron/BEH-AXO.md +++ b/neuron/BEH-AXO.md @@ -23,8 +23,6 @@ container: BEH-AXO ## BEH-PRE: Container -**High level description**: - The presynapse is the sending terminal of a neuron — a small bulb at the tip of an axon whose job is to release chemical signals, called neurotransmitters (NT), into the synaptic cleft, the narrow gap that separates it from the receiving neuron's postsynapse. To do this, the presynapse maintains a stockpile of NT packed inside small membrane bubbles called vesicles. These vesicles are organised in two pools: a reserve pool (RP), which is the deep storage, and a readily-releasable pool (RRP), which is the small set of vesicles docked at the membrane and ready to fire immediately. When a spike arrives — an electrical pulse called an action potential — it briefly opens specialised calcium channels (VGCCs) in the membrane. Calcium (Ca²⁺) rushes in, and the sudden local surge of calcium triggers the docked vesicles to fuse with the membrane and pour their NT into the cleft. @@ -90,9 +88,9 @@ In this first comprehension, we decide to simplify: The simplification impies that: -- Removing CDI and mGluR means Ca²⁺ concentration and NT_cleft are now the only two variables controlling release rate. This is cleaner and matches your fast/medium/slow framing directly — the release rate table from earlier becomes the core logic of the ms loop. +- Removing CDI and mGluR means Ca²⁺ concentration and NT in the cleft are now the only two conditions controlling release rate. -- Removing ATP removes the metabolic silencing cascade entirely. The mins loop now only does one thing: replenish the NT reserve. If you want the synapse to still be able to fail under sustained firing, the mechanism would have to come from NT depletion alone (RP exhausted, nothing to replenish) rather than from pump failure and Ca²⁺ accumulation. +- Removing ATP removes the metabolic silencing cascade entirely. The mins loop now only does one thing: replenish the NT reserve. If we want the synapse to still be able to fail under sustained firing, the mechanism would have to come from NT depletion alone (RP exhausted, nothing to replenish) rather than from pump failure and Ca²⁺ accumulation. - "Ca²⁺ cleared slowly" replaces PMCA, NCX, and SERCA with a single exponential decay. This means Ca²⁺ will still accumulate under high firing if the decay is slow relative to the spike rate, which preserves some of the residual-Ca²⁺ dynamic even without the full pump machinery. @@ -123,8 +121,11 @@ The simplification impies that: **— mins:** -- Glucose level sets conversion_efficiency +- Glucose level sets base conversion_efficiency +- If astrocyte wave was triggered → conversion_efficiency boosted temporarily - Glutamine shuttle refills NT reserve from astrocyte store + (faster if wave active, baseline if not) +- Wave boost decays back to baseline over subsequent cycles **Tubs:**