20 KiB
What needs adjustment
Voltage-Context is labelled as an Episode but contains sub-episodes — it should be a Context. Same for NMDA-Coincidence and Ca-Dynamics & ATP-Drain. You have used Episode and Context interchangeably in a few places; the distinction matters for the specification: a Context sets the conditions, an Episode is a named outcome within those conditions.
Vpost_Maximum lists V_bAP full OR (g_AMPA full AND V_bAP medium) — this is correct Boolean logic and should be kept exactly as written. It captures the two ways the postsynapse can reach maximum depolarisation: the bAP alone if it is strong enough, or AMPA plus a partial bAP together.
AMPA_Population_Increase correctly gates on ATP_level_post NOT empty — LTP requires ATP for CaMKII phosphorylation and receptor trafficking. LTD does not have the same gate in your spec. This is slightly asymmetric — LTD (receptor internalisation via endocytosis) is also ATP-dependent, though less so than LTP. Worth noting.
Plasticity_LTD covers Ca_post_history medium but does not cover the case where Ca_post_history is empty — a completely silent synapse also weakens over time (homeostatic depression). This can be left as a gap or named explicitly.
Astrocyte_Supply_Crises has a typo (Crises → Crisis).
The bAP needs new parameters and state variables in the model before it can be expressed as a fully implemented behavior. I will add those inline as [GAP — to implement] markers so the spec is complete even where the code is not yet written.
Final restructured specification
BEH-POST-UNIFIED: The Integrated Postsynaptic Model
=====================================================
Three loops, three timescales, one shared astrocyte supply.
Each loop feeds the next: V_post enables NMDA, NMDA drives
Ca_post, Ca_post determines plasticity and eCB, ATP sustains
all three. Failure of ATP does not silence the postsynapse
(unlike the presynapse) — it corrupts it, triggering false
retrograde signals and risking excitotoxic Ca2+ accumulation.
Variables:
V_bAP — back-propagating AP amplitude (0→1)
[GAP — requires bAP_train input,
analogous to presynaptic spike_train]
g_AMPA — AMPA receptor conductance (= receptor_conductance)
V_post — total postsynaptic membrane potential (0→1)
NT_cleft — glutamate in cleft (from presynapse)
Desensitization — fraction of AMPA receptors desensitized (0→1)
Ca_post — free Ca2+ in postsynaptic spine (0→...)
Ca_post_history — 2 s rolling mean of Ca_post
ATP_level_post — normalised postsynaptic ATP (0→1)
ATP_demand_post — accumulated ATP cost since last metabolic cycle
g_AMPA_baseline — long-term AMPA receptor density set by plasticity
[GAP — not yet in model; LTP/LTD would write this]
eCB_level — endocannabinoid retrograde signal (0→1)
written here, read by presynapse Loop 1
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ms: behaviors — Fast Kinetics and Gate Logic
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Voltage-Context: Context
Determines the total depolarisation (V_post) available to
lift the NMDA Mg block. Two independent sources contribute:
AMPA-driven local depolarisation (g_AMPA) and the somatic
back-propagating AP (V_bAP). Either alone can partially
depolarise; both together reach maximum.
Vpost_Maximum: Episode
— V_bAP full OR
— g_AMPA full AND V_bAP medium
— Result: V_post high enough for complete Mg block removal.
NMDA gate can open fully.
Both ATP costs charged at maximum rate.
Vpost_Attenuated: Episode
— g_AMPA medium AND V_bAP empty/low OR
— g_AMPA low AND V_bAP medium
— Result: V_post sub-threshold.
Mg block partially remains.
NMDA gate opens partially or not at all.
This is the most common state during low-rate firing
without a coincident bAP.
Vpost_Passive: Episode
— g_AMPA empty AND V_bAP empty
— Result: V_post at rest.
Mg block fully intact.
No Ca_post entry possible.
Na/K-ATPase cost minimal.
Desensitization-Context: Context
Modulates g_AMPA independently of NT_cleft.
Sustained NT exposure drives receptors into a closed state
that persists even when NT remains present.
DesensitizationRising: Episode
— NT_cleft sustained high (multiple consecutive ms)
— Desensitization rises each ms
— g_AMPA effectively reduced despite NT presence
— attenuates Vpost_Maximum toward Vpost_Attenuated
DesensitizationRecovering: Episode
— NT_cleft low or empty
— Desensitization decays with tau_desensitization = 500 ms
— g_AMPA ceiling restored gradually
NMDA-Coincidence: Context
Strict AND gate: both NT (ligand) and V_post (voltage) must
be simultaneously non-zero for Ca_post to rise.
Unlike presynaptic VGCCs which open with any spike, NMDA
requires coincidence. This makes Ca_post a detector of
coordinated pre+post activity, not just input rate.
NMDA_Open: Episode
— NT_cleft full AND V_post maximum (Vpost_Maximum active)
— Mg block fully lifted
— Ca_post surges — LTP territory
— ATP_demand_post rises sharply (PMCA must clear Ca_post)
— if sustained → Ca_post_history crosses eCB threshold
NMDA_LogicBlocked: Episode
— NT_cleft full BUT V_post attenuated or passive
— Mg block partially or fully intact
— Ca_post does not rise despite NT presence
— Result: presynapse fired but postsynapse was not ready
No plasticity signal generated
This is the mechanism for input selectivity:
only synapses active during postsynaptic firing
produce a Ca_post signal
NMDA_LigandBlocked: Episode
— V_post maximum BUT NT_cleft empty
— No glutamate to open the channel
— Ca_post entry zero despite full depolarisation
— Result: bAP arrived but presynapse was silent
Again no plasticity signal
The AND logic enforces true coincidence
Ca-Dynamics-Context: Context
Ca_post clearance rate depends entirely on ATP_level_post.
This is the bridge from the ATP loop into the Ca2+ loop.
When ATP fails, Ca_post clearance fails, and the Ca2+ loop
becomes corrupted — Ca_post reflects pump state rather
than genuine coincidence events.
Clearance_Optimal: Episode
— ATP_level_post full → pump_scale_post near 1
— PMCA (ATP-gated) + NCX (always on) both clearing
— Ca_post returns to baseline between events
— Each coincidence event is temporally isolated
— ATP_demand_post increases proportionally to Ca_post load
Clearance_Reduced: Episode
— ATP_level_post medium → pump_scale_post reduced
— Ca_post clears more slowly
— Residual elevation begins accumulating between events
— Ca_post_history starts drifting upward
— eCB threshold may be approached during heavy firing
Clearance_Failing: Episode
— ATP_level_post low or empty → pump_scale_post near 0
— Only NCX clearing (floor, not rescue)
— Ca_post accumulates regardless of coincidence activity
— False Trigger conditions: Ca_post_history crosses eCB
threshold without genuine NMDA overactivity
— Excitotoxicity risk if Ca_post elevation is sustained
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sec: behaviors — Signal Integration and Fate
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Synaptic-Weight-Decision: Context
Ca_post_history (2 s rolling mean of Ca_post) determines
the plasticity signal. The threshold logic is graded:
the same variable produces opposite outcomes depending
on whether it is above or below the LTP/LTD boundary.
ATP_level_post gates LTP expression but not LTD —
strengthening requires energy, weakening does not.
Plasticity_LTP: Episode
— Ca_post_history full (above Ca_post_LTP threshold)
— High-frequency or high-amplitude coincidence detected
— Tags synapse for AMPA receptor insertion
— Requires ATP_level_post NOT empty for expression
(CaMKII phosphorylation and receptor trafficking are
ATP-dependent — energy failure blocks LTP even if
the Ca_post signal is correct)
— [GAP] LTP expression writes g_AMPA_baseline upward
in the minutes loop
Plasticity_Boundary: Episode
— Ca_post_history medium
— Poorly timed or low-frequency coincidence
— Neither LTP nor LTD threshold crossed
— Synapse weight unchanged this cycle
Plasticity_LTD: Episode
— Ca_post_history low but non-zero
— Weak or mistimed coincidence — presynapse fired
but postsynapse was not sufficiently depolarised
— Tags synapse for AMPA receptor removal
— Less ATP-dependent than LTP; can proceed under
mild energy stress
— [GAP] LTD expression writes g_AMPA_baseline downward
in the minutes loop
Plasticity_Silent: Episode
— Ca_post_history empty (prolonged absence of activity)
— Homeostatic depression: unused synapses weaken
— [GAP] not yet modelled; would require Ca_post_trace
integration over hours
Retrograde-Feedback: Context
eCB synthesis is triggered by Ca_post_history, not V_post.
It is Ca2+ in the spine — not voltage — that activates the
enzymes (DAGL, PLC) that produce endocannabinoids.
The model cannot distinguish internally between the two
causes of elevated Ca_post_history (genuine vs pump failure)
but the consequences differ: one is communication,
the other is survival.
eCB_Synthesis_Active: Episode
— Ca_post_history > eCB_threshold (0.7)
— Logic A (Genuine Protection):
Cause : sustained NMDA_Open events — real overactivity
Effect : appropriate retrograde stop signal
Outcome : presynapse reduces NT → NT_cleft falls →
NMDA closes → Ca_post load drops →
Ca_post_history falls → eCB synthesis subsides
Loop closes correctly
— Logic B (False Trigger — Excitotoxic Protection):
Cause : Clearance_Failing — Ca_post elevated by
pump failure, not genuine coincidence
Effect : presynapse silenced without real overactivity
Outcome : NT_cleft falls → NMDA closes → Ca_post
load drops → ATP_demand_post falls →
ATP_level_post recovers → pumps restart →
Ca_post clears → Ca_post_history falls →
eCB synthesis subsides
Desperate survival loop — buys time for
metabolic recovery
eCB_Synthesis_Idle: Episode
— Ca_post_history < eCB_threshold
— eCB_level decays with tau_eCB_decay = 10000 ms
— Presynaptic suppression lifts gradually
— 10 s decay means suppression outlasts the trigger —
prevents immediate re-engagement before Ca_post
has stabilised
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min: behaviors — Bioenergetics and Structural Change
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Metabolic-Recovery: Context
ATP_level_post is computed from Glucose_level (shared
supply) minus ATP_demand_post (postsynaptic-specific cost).
The shared supply creates the coupling: both pre and post
deplete the same astrocyte glucose budget simultaneously.
Presynaptic silence is therefore metabolically beneficial
to the postsynapse — less NT means less NMDA activation
means less Ca_post means less PMCA cost.
Astrocyte_Supply_Active: Episode
— Glucose_level full
— ATP_demand_post within supply capacity
— ATP_level_post replenished each cycle
— All three loops operating normally
Astrocyte_Supply_Stressed: Episode
— Glucose_level medium OR ATP_demand_post elevated
— ATP_level_post partially reduced
— Clearance_Reduced begins
— Plasticity_LTP at risk (ATP dependency)
Astrocyte_Supply_Crisis: Episode
— Glucose_level low OR ATP_demand_post chronically high
— ATP_level_post near empty
— Clearance_Failing — only NCX clearing Ca_post
— False Trigger likely → eCB_Synthesis_Active (Logic B)
— Presynaptic silence indirectly reduces postsynaptic
ATP demand — the coupled protection mechanism
Structural-Update: Context
Long-term changes to AMPA receptor density.
These are the physical substrate of learning and memory.
[GAP] g_AMPA_baseline not yet implemented in the model.
Would be written in Loop 3 and read by Loop 1 as the
ceiling of receptor_conductance.
AMPA_Population_Increase: Episode
— Triggered by Plasticity_LTP
— AND ATP_level_post NOT empty
— g_AMPA_baseline shifts higher for next cycle
— More AMPA receptors → stronger Vpost_Maximum
— Easier to reach NMDA_Open in future events
— Positive feedback: LTP makes future LTP more likely
AMPA_Population_Decrease: Episode
— Triggered by Plasticity_LTD or Plasticity_Silent
— g_AMPA_baseline shifts lower
— Fewer AMPA receptors → Vpost_Attenuated more common
— Harder to reach NMDA_Open → weakens synapse further
— Negative feedback: LTD stabilises by reducing
future coincidence probability
short term
Short-term potentiation (STP) and short-term depression (STD) are distinct from LTP/LTD in a fundamental way: they are temporary changes that last seconds to minutes and leave no lasting structural trace. They do not require the postsynapse at all — they are entirely presynaptic phenomena in most cases, and they operate on a completely different mechanism.
What they are and where they live
Short-term plasticity is driven by the history of presynaptic Ca²⁺ and vesicle pool state, not by postsynaptic coincidence detection. The table we just built describes long-term plasticity — structural changes to AMPA density driven by Ca_post. Short-term plasticity describes transient changes to how much NT the presynapse releases on the next spike, driven by what happened on the last few spikes.
There are two opposing forms:
Short-term potentiation / facilitation — if a spike arrives shortly after the previous one, residual Ca²⁺ from the first spike has not fully cleared. The next spike adds to this residual, producing a larger Ca_post microdomain and therefore a higher release probability. The synapse releases more NT on the second spike than the first. This is already partially captured in the presynaptic model through Tr_Ca — elevated calcium trace from recent activity speeds up RRP recruitment and effectively increases release efficiency.
Short-term depression — if spikes arrive rapidly, the RRP depletes faster than it can be refilled. Each successive spike releases fewer vesicles because there are fewer available. NT release drops with each spike in a burst. This is already the core of CASCADE 1 in the presynaptic model — RRP depletion under high firing rate.
Where they fit in the model
Both are already implicitly present in the presynaptic ms and seconds loops:
Short-term facilitation:
Residual Ca_micro from spike N
→ elevated Ca_micro at spike N+1
→ higher release fraction in deterministic_release (Hill curve)
→ more NT per spike
→ decays as Ca_micro clears between spikes (tau ~100-200 ms)
Short-term depression:
Rapid firing depletes N_RRP
→ fewer vesicles available per spike
→ released_NT falls
→ recovers as RP→RRP recruitment refills (seconds timescale)
The timescale of each depends on parameters already in the model:
| Form | Timescale | Driven by | Recovery |
|---|---|---|---|
| Facilitation | 100-500 ms | residual Ca_micro | Ca²⁺ clearance rate |
| Depression | seconds | RRP depletion | RP→RRP recruitment rate |
What is missing from the current model
The model captures both implicitly but does not name them as behaviours. Two things are genuinely absent:
Augmentation — a slower form of facilitation lasting 5-10 seconds, driven by residual Ca²⁺ accumulating in the presynaptic terminal across many spikes. It is distinct from spike-by-spike facilitation and would require a second, slower Ca²⁺ trace with tau ~5000 ms. The current Tr_Ca with tau = 1000 ms is between the two — it captures some augmentation but not cleanly.
Post-tetanic potentiation (PTP) — an even slower presynaptic enhancement lasting minutes after a high-frequency burst, driven by protein kinase C activation from sustained Ca²⁺ elevation. This is a presynaptic phenomenon that looks like LTP from the outside but has no postsynaptic component and no structural change. It would require a third, very slow trace variable.
How they interact with the LTP/LTD table
Short-term and long-term plasticity operate on the same synapse simultaneously but independently:
Spike arrives
→ short-term: how much NT releases THIS spike (presynaptic, ms-seconds)
→ long-term: does the synapse get stronger or weaker PERMANENTLY (postsynaptic, mins-hours)
A synapse can be undergoing LTD (slowly losing AMPA receptors over minutes) at the same time as it is showing short-term facilitation (releasing more NT per spike due to residual Ca²⁺). The two processes do not interfere — they act on different variables through different mechanisms.
The important implication for your model is that the LTP/LTD table we built describes what happens to g_AMPA_baseline over minutes. Short-term potentiation/depression describes what happens to released_NT over milliseconds to seconds. They are different outputs of the same synapse, running in parallel.
If you want to add short-term plasticity explicitly to the behaviour specification it would live entirely in the presynaptic ms and seconds loops as named episodes of existing variables:
— ms (presynapse, short-term plasticity):
ShortTermFacilitation: Episode
— residual Ca_micro > 0 at next spike arrival
— release_frac in deterministic_release elevated above baseline
— decays as Ca_micro clears (tau ~100-500 ms)
— more NT per spike than at rest
ShortTermDepression: Episode
— N_RRP depleted by rapid successive spikes
— release_frac unchanged but N_RRP reduced
— fewer absolute vesicles released per spike
— recovers via RP→RRP recruitment (seconds)
— seconds (presynapse, short-term plasticity):
Augmentation: Episode [GAP — not yet modelled]
— requires second slow Ca2+ trace (tau ~5000 ms)
— elevated release probability for 5-10 s after burst
— distinct from spike-by-spike facilitation
PostTetanicPotentiation: Episode [GAP — not yet modelled]
— requires very slow trace (tau ~minutes)
— elevated release probability for minutes after tetanus
— presynaptic only, no postsynaptic component