Mod 4 - Neuroplasticity

What happens to synaptic potential size when the NUMBER of active synapses changes?

More simultaneously active synapses → more quanta released and more postsynaptic receptor activation → larger summed EPSP; fewer active synapses → smaller summed EPSP. Larger spine heads usually host more AMPARs, further boosting EPSP amplitude. Mnemonic: “More plugs = more power.”

How does PROBABILITY OF RELEASE (Pr) change EPSP size?

Higher Pr (more docked vesicles + higher nanodomain Ca²⁺) → more vesicles fuse per spike → larger mean EPSP; lower Pr → smaller, more variable EPSPs. Release is quantal and stochastic; typical Pr < 1. Flow: Docked vesicles + Ca²⁺ → Fusion → Glutamate → EPSP. Mnemonic: “Pr powers postsynaptic punch.”

How do POSTSYNAPTIC RECEPTOR LEVELS shape synaptic potential?

↑ AMPAR number/conductance → more Na⁺/K⁺ current → bigger EPSP; NMDARs are Ca²⁺ permeable coincidence detectors (Mg²⁺ block at rest), key for plasticity induction rather than baseline EPSP. Subunit composition tunes kinetics/permeability. Mnemonic: “AMPA = Amplify; NMDA = Need depolarisation.”

How do neurons integrate information?

Thousands of weak inputs combine by spatial + temporal summation; coincident EPSPs (overlap in time and space) can reach threshold to trigger an AP. Neurons effectively perform logic operations (“integrate and fire”). Flow: EPSPs → Sum (time + space) → Threshold → AP.

How do synaptic strength and intrinsic excitability determine output?

Output ≈ synaptic drive × excitability. Stronger synapses produce larger EPSPs; higher intrinsic excitability (e.g., fewer K⁺ conductances) lowers spike threshold so the same input yields more spikes (E–S potentiation). Mnemonic: “Strength loads; excitability fires.”

How can changes in synaptic strength mediate associative learning?

Co activation of weak + strong pathways relieves NMDAR Mg²⁺ block at the weak synapse during glutamate binding → Ca²⁺ influx → LTP at that synapse. After pairing, the weak cue alone evokes larger responses (Pavlovian fear: tone + shock). Flow: Weak + Strong → NMDA Ca²⁺ at weak synapse → AMPAR up → bigger EPSP → learned response. Mnemonic: “Fire together, wire together.”

What are the CORE COMPONENTS required for LTP?

AMPARs (fast EPSPs/expression site), NMDARs (voltage gated Ca²⁺ entry/coincidence detection), intracellular Ca²⁺ (trigger), kinases (e.g., CaMKII), late phase gene transcription/protein synthesis, structural changes (spine growth), and maintenance mechanisms (PKM ζ). Mnemonic: “AMPA expresses, NMDA induces, Ca²⁺ commands, PKM ζ preserves.”

What is the SEQUENCE OF EVENTS for LTP induction (weak vs strong vs paired)?

Weak alone: AMPAR EPSPs; NMDAR blocked; little Ca²⁺. Strong alone: summated AMPAR EPSPs → depolarisation → NMDAR unblock → large Ca²⁺. Paired: strong input depolarises cell; at co active weak synapses NMDARs open during glutamate binding → local Ca²⁺ rise → LTP. Flow: Glutamate → AMPA depol → NMDA unblock → Ca²⁺ in → CaMKII → AMPAR phosphorylation/insertion → larger EPSP.

What roles do key elements play in LTP INDUCTION, EXPRESSION, and MAINTENANCE?

Induction: depolarisation + NMDAR Ca²⁺; CaMKII activation. Expression: ↑ AMPAR number/conductance, ± ↑ Pr, ± new/stronger synapses; spine head enlargement. Maintenance: late LTP needs new proteins/genes; PKM ζ sustains potentiation; blocking PKM ζ (e.g., ZIP) can erase it. Mnemonic: “Induce with Ca²⁺, Express with AMPA, Maintain with PKM ζ.”

What is LTD and how is it induced?

Low frequency stimulation (e.g., ~1 Hz) → modest, prolonged Ca²⁺ entry → phosphatase cascade (dephosphorylation) → AMPAR endocytosis → decreased synaptic efficacy. Ca²⁺ amplitude/duration sets the ‘switch’: big/brief = LTP; small/prolonged = LTD. Mnemonic: “High Ca²⁺ builds, low Ca²⁺ breaks.”

What is the ROLE OF SPINES in plasticity?

Excitatory synapses sit on dendritic spines; the thin neck restricts diffusion so Ca²⁺/signalling stay local → input specificity. LTP typically enlarges spine heads (more AMPARs); LTD shrinks them. Abnormal spine structure is linked to cognitive issues. Flow: Input → Spine Ca²⁺ microdomain → Local LTP/LTD → Structural match.

What OTHER learning

related cellular changes occur beyond LTP/LTD? Intrinsic excitability: persistent ↓ in specific K⁺ currents → more spikes for same input (cell wide, not synapse specific). Neurogenesis: adult hippocampus adds new neurons; blocking proliferation impairs hippocampal dependent learning. Mnemonic: “Plasticity = Synapses + Excitability + New neurons.”

How does plasticity relate to learning, and what happens if we BLOCK CORE COMPONENTS (predict effects)?

Block NMDARs or Ca²⁺ entry → fail to induce LTP → impaired acquisition. Block CaMKII/AMPAR trafficking → impaired expression. Block protein synthesis/transcription → no late consolidation. Block PKM ζ → erase established potentiation/memory. Block LTD/phosphatases → poor updating/erasure of outdated traces; interference increases. Mnemonic: “No NMDA/Ca²⁺, no learn; no proteins, no keep.”

What are the STAGES to form lasting memories?

Sensory memory (ms–s; iconic/echoic) → Short term/working memory (<1 min, ~7±2 items; rehearsal/chunking help) → Consolidation (protein synthesis/gene regulation) → Long term storage (days–lifetime) → Retrieval (reconstructive). Flow: Sensory → STM/WM → Consolidation → LTM → Retrieval.

What principles of memory organisation come from patient H.M.?

Bilateral MTL (hippocampus + amygdala + surrounding cortex) resection → profound anterograde amnesia and some retrograde loss; intact short term span and motor learning (mirror tracing). Shows hippocampus is required to FORM new declarative memories but is not the permanent storage site. Mnemonic: “H.M. = Hippocampus Missing → new memories missing.”

How do DIFFERENT MEMORY SYSTEMS map to brain structures?

Declarative (episodic/semantic): hippocampus + MTL cortices with distributed cortical storage (place cells for space). Procedural/skills & habits: cortico–basal ganglia circuits (striatum), cerebellum; support chunking/automatization and are spared in hippocampal amnesia but impaired in basal ganglia disease (e.g., Huntington’s). Working memory: prefrontal cortex. Emotional memory: amygdala. Mnemonic: “Facts=HPC, Skills=Striatum, Working=PFC, Emotion=Amygdala.”

What is CONSOLIDATION vs RECONSOLIDATION?

Consolidation stabilises new memories post learning via protein synthesis and systems level reorganisation. Reconsolidation: reactivated memories become transiently labile and require restabilisation; during this window, traces can be strengthened, updated, or weakened/erased. Mnemonic: “Consolidate = save; Reconsolidate = edit.”

Why are memories DYNAMIC, not static?

Memory is reconstructive and context sensitive (misinformation can distort; false memories can be implanted). Normal forgetting prunes outdated info; updating promotes relevant info to prevent interference. Mnemonic: “Memory isn’t a photo; it’s Photoshop.”

How does ACETYLCHOLINE help adapt behaviour to changing circumstances?

ACh helps “interlace” overlapping memories, biasing networks toward encoding current context and reducing interference with older traces; supports flexible switching between encoding vs retrieval modes. Flow: Context shift → ↑ACh → distinct encoding → less interference.

How do DOPAMINE and prediction error contribute to memory updating?

Dopamine neuron activity tracks surprise (expected vs actual outcome mismatch), signalling when to adjust synaptic weights and update action–outcome memories; crucial for extinction and adaptive learning. Mnemonic: “DA = Difference Announcer.”

What is EXTINCTION and how is it implemented neurally?

Extinction (CS without US) forms a new inhibitory memory that suppresses the old one rather than erasing it; corticostriatal circuits (incl. D2 pathway neurons) are involved—disruptions here impair extinction learning. Flow: Reactivate → Expectation violated → New inhibitory trace.

Why is RECONSOLIDATION clinically relevant (psychiatric treatment)?

Intervening as a memory is reactivated can weaken maladaptive memories: e.g., propranolol before reactivation reduces fear expression; protein synthesis blockers (in animals) or ECT protocols can impair specific reactivated memories; extinction procedures during the reconsolidation window aid PTSD/phobias/substance use treatments. Mnemonic: “Reactivate → Rewrite → Relief.”

How do SPINE dynamics and LTP/LTD support associative learning evidence

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What experimental manipulations LINK LTP like plasticity to real learning?

NMDAR antagonists (APV/MK 801) block acquisition but not expression; inhibiting protein synthesis during/after learning causes amnesia hours later; disrupting PKM ζ erases recent/remote memories; optogenetically pairing tone with depolarisation in amygdala can “implant” a de novo fear memory. Flow: Block induction → no learn; block maintenance → no keep; artificial pairing → artificial memory.

How do CHANGES IN INTRINSIC EXCITABILITY contribute to learning differently from LTP?

Learning often reduces certain K⁺ conductances, shifting the f–I curve so the same EPSP yields more spikes (E–S potentiation). This is cell wide (not synapse specific), complementing synapse specific LTP/LTD. Mnemonic: “Less K⁺, more spikes.”

What is the MULTI STORE MODEL and core store properties?

Sensory registers (iconic ~300–500 ms; echoic up to ~4 s) feed STM/WM (capacity limited; rehearsal/chunking extend utility), then consolidation commits traces to LTM (vast capacity; retrieval limited). Supports clinical observations (e.g., H.M. intact span but impaired long term formation). Mnemonic: “See → Hold → Save.”

How do BASAL GANGLIA circuits support SKILL learning and automatization?

Practice compresses action sequences into “chunks,” shifting control to cortico–basal ganglia loops; early actions are sparse/distributed, later compact/efficient. Striatal dysfunction (e.g., Huntington’s) impairs sequencing and habit formation. Mnemonic: “Striatum strings steps.”

What distinguishes AMPA vs NMDA receptor function at excitatory synapses?

AMPARs: fast, voltage insensitive, Na⁺/K⁺ (±Ca²⁺) permeable; scale with synapse size; mediate baseline EPSPs and LTP expression. NMDARs: slower, Mg²⁺ blocked at rest, Ca²⁺ permeable; serve as coincidence detectors for induction (LTP/LTD). Mnemonic: “AMPA = drive; NMDA = decide.”

What is the CALCIUM ‘decision rule’ for LTP vs LTD?

Brief/high, spine localised Ca²⁺ transients favour kinases (e.g., CaMKII) → LTP; lower/prolonged Ca²⁺ favours phosphatases → LTD. Spine geometry + NMDAR gating set these signatures. Mnemonic: “Ca²⁺ height decides the rewrite.”

What are the PRACTICAL CONSEQUENCES of blocking LTD components?

Impaired weakening/pruning of outdated synapses → interference, rigid behaviour, reduced discrimination and flexibility; networks become biased toward potentiation and can retain maladaptive associations. Mnemonic: “No LTD = No Letting go.”

What are the processes and stages needed to form lasting memories?

Info flows through a multistore pipeline: sensory registers hold raw input for ms–s (iconic ~300–500 ms; echoic up to ~4 s) → short term/working memory keeps a small amount (<1 min; capacity ~7 ± 2; rehearsal & chunking help) → consolidation transforms labile traces into stable long term memory via protein synthesis/gene regulation → retrieval reconstructs the stored trace. Flow: sensory → STM/WM → consolidation → LTM → retrieval. Mnemonic: “See → Hold → Save → Store → Summon.”

What did patient H.M. reveal about how memory is organised?

After bilateral medial temporal lobe resection (hippocampus + amygdala + surrounding cortex), H.M. had profound anterograde amnesia and some retrograde loss, with normal IQ/perception. He could retain a short digit span with rehearsal but failed when distracted, and he could still learn skills (mirror tracing). Conclusion: MTL/hippocampus is required to form new declarative memories but is not the permanent storage site; multiple memory systems exist. Mnemonic: “H.M. = Hippocampus Missing → new memories missing.”

How do different memory systems and their brain structures differ?

Declarative (episodic/semantic): hippocampus + medial temporal cortices with distributed cortical storage; episodic & spatial navigation recruit hippocampus, parahippocampal, prefrontal, lateral & parietal cortices; place cells give a cognitive map. Procedural/skills & habits: cortico basal ganglia circuits (striatum) support sequencing/chunking and are relatively spared in hippocampal amnesia; basal ganglia disease (e.g., Huntington’s) impairs these. Working memory: prefrontal cortex. Emotional memory: amygdala. Mnemonic: “Facts=HPC; Skills=Striatum; Working=PFC; Emotion=Amygdala.”

What is memory consolidation and how does it differ from reconsolidation?

Consolidation: post learning stabilisation of new memories into LTM; depends on protein synthesis and gene expression. Reconsolidation: when a stored memory is reactivated, it becomes labile again and must be restabilised; during this window, it can be strengthened, updated, or weakened. Mnemonic: “Consolidate = Save; Reconsolidate = Edit.”

Why are memories dynamic, flexible, and open to change?

Memory is reconstructive and prone to error: misinformation can distort originals, and strong suggestions can implant false memories. Normal forgetting prunes outdated info; updating promotes newer, relevant content and reduces interference. Mnemonic: “Not a photo—Photoshop.”

How does acetylcholine help adapt behaviour when circumstances change?

Acetylcholine (ACh) helps interlace overlapping memories, reducing interference and biasing networks toward encoding the current context rather than retrieving outdated traces; supports flexible switching of cognitive states. Flow: context shift → ↑ACh → distinct encoding → less interference.

Why is reconsolidation and memory updating clinically useful?

Intervening at reactivation can weaken maladaptive memories: in animals, protein synthesis blockade after reactivation can erase fear traces; ECT can debilitate specific memories; in humans, propranolol before reactivation reduces fear expression; extinction based updating is effective for PTSD and specific phobias and shows promise for anxiety and substance use disorders. Flow: reactivate → update/attenuate → relief.

How do dopamine signals and extinction contribute to memory updating?

Dopamine neurons signal prediction error (surprise) when outcomes differ from expectations, gating plasticity for updating; extinction (CS without US) forms a new inhibitory memory that suppresses the old association. Disrupting striatal D2 circuits impairs extinction based updating. Mnemonic: “DA = Difference Announcer.”

Process wise, what’s the difference between consolidation and reconsolidation?

Consolidation occurs after initial learning: labile trace → protein synthesis/gene regulation → systems level redistribution → stable LTM. Reconsolidation occurs after retrieval/reactivation: stable trace becomes labile again → requires protein synthesis to restabilise → is modifiable (can strengthen, update, or weaken). Flow: Learn→Save vs. Recall→Open→Edit→Resave. Mnemonic: “Save once (consolidation); reopen to edit (reconsolidation).”