LEARNING & MEMORY: FUNCTIONAL PERSPECTIVES, L5-P2

LEARNING & MEMORY: FUNCTIONAL PERSPECTIVES, L5-P2

1. MEMORY STORAGE REQUIRE NEURONAL REMODELLING

   • structural changes at the synapse may provide long-term storage, new synapses could form, or some could be eliminated with training - training might also lead to synaptic reorganisation

2. DONALD HEBB (1904-1985)

   • Hebb’s law: synapses grow stronger by changing chemically or structurally when the presynaptic neuron repeatedly causes the postsynaptic cell to fire
   • Hebbian synapse: a synapse that is strengthened when it successfully drives the postsynaptic cell
   • CELLS THAT FIRE TOGETHER, WIRE TOGETHER – CREATE LINK THAT ALLOWS LEARNING TO HAPPEN

3. LONG-TERM POTENTIATION (LTP)

   • A stable and enduring increase in the effectiveness of synapses (synaptic strength):
     • - A single pulse is applied in the presynaptic neuron (baseline measure) - A strong burst of electrical stimulation (tetanus) is then applied: triggers thousands of action potentials – LTP induction
       • - A single pulse is again applied and the magnitude of EPSP in the postsynaptic neuron is measured: o Increase in the amplitude of the EPSP in the postsynaptic neuron o Can lst for days to weeks o First recorded in hippocampus by Bliss and Lomo in 1973 o Also found in other structures such as amygdala, basal ganglia and cerebellum o If pulses presented slowly (low frequency), opposite effect develops: long term depression (LTD)

4. GLUTAMATE

   • - Most abundant - Major excitatory transmitter in the brain - Glutamatergic transmission uses AMPA and NMDA receptors - AMPA: regular ionotropic receptors - NMDA: normally blocked by Magnesium (Mg2+) - Because the NMDA receptor pore is blocked by a magnesium ion, release of glutamate by a weak electrical stimulation activates only the AMPA receptor - Glutamate first activates AMPA receptors
     • o NMDA receptors do not respond until enough AMPA receptors are stimulated, and the neuron is partially depolarised o After partial depolarisation, the block is removed, and the NMDA receptors allows Ca2+ to enter in response to glutamate
       • ROLES OF THE NMDA AND AMPA RECEPTORS IN THE INDUCTION OF LTP
         • A strong electrical stimulation can depolarise the postsynaptic membrane sufficiently that the magnesium ion is removed from the NMDA receptor pore The large Ca2+ influx activates certain protein kinases – namely CaMKII (calcium-calmodulin kinase II) CaMKII causes more AMPA receptors to be produced and inserted in the postsynaptic membrane CaMKII also increases the efficacy of current AMPA receptors
         • THE 8 STEP PROCESS
           • (1) Normal function = AMPA receptor activity (2) Increased action potentials = more AMPA receptor activity (3) Postsynaptic membrane starts to depolarise (4) Mg2+ pops out of NMDA receptors (5) Influx of Ca2+ (6) CA2+ causes activation of CamKII (7) CamKII increases AMPA receptors on membrane (8) More AMPA receptors means that communication between the neurons has just improved – learning has occurred!

5. PATTERN OF COMMUNICATION OF NEURONS IS WHAT HAPPENS WHEN ENCODE MEMORY

   • BUT DOES LTP = MEMORY?
     • THERE IS EVIDENCE THAT LTP MAY BE ONE PART OF LEARNING AND MEMORY FORMATION: - Correlational observation – time course of LTP is similar to that of memory formation - Somatic intervention experiments – pharmacological treatments that block LTP impair learning - Behavioural intervention experiments – training an animal in a memory task can induce LTP