learning and memory

• Hebb rule: when an axon of cells is near enough to excite cell b and repeatedly or persistently takes part in firing it, some growth or metabolic change takes place in both sells such that a’s efficiency as one of the cells firing b is increase 

  Principles - locality and joint activity
• Short term plasticity: rapid changed in strength of EPSP that do not persist longer than a second
• Long term plasticity: a long-lasting, activity-dependent change in synaptic efficacy
• Synaptic plasticity: 

  Changes in the unity of neurotransmitter release into a synapse and changes in how effectively cells respond to those neurotransmitters
• Spike dependent plasticity  - timing between when neurons fire matters 

  • Critical time window for when we see this plasticity process 
  • Stimulate electrons one by one with specific frequency and measure difference between first and second pulse
• Synaptic tag and capture - flag the learning pathway and then you have a stronger experience that cement the change that happens with the pathway
• Structural vs. functional plasticity 

  Structural: generation of new connections

  Functional: changin strength of existing connections
• What is memory?

  • Memory is the knowledge of a former state of mind
• Sensory memory - milliseconds to seconds 

  Short term memory - seconds to minutes 

  Long term memory - days to years
• Declarative memory (explicit)

  • Episodic memory (events) 
  • Can go back in time and know who was

  there and what you were doing 

  • Where when and what
• Declarative memory (explicit)

  Semantic memory (facts) 

  • Don’t know how you know it
• Non declarative memory (implicit memory) 

  • Procedural (motor and cognitive skills)
  • Perceptual (perceptual priming)
  • Classical conditioning (conditioned responses between two stimuli) 
  • Non associative (habituation sensitization)
• Phases of long term memory: 

  1. Encoding
  2. Consolidation 
  3. Retrieval
• Anterograde amnesia - inability to form new memories
• Retrograde amnesia - inability to recollect old memories
• HM patient 

  Surgery to alleviate seizures lead to inability to create new memories
• PKM zeta - acts as glue for fixing connections between synapses so that later the experience can be reactivated
• H++ has more damage to the hippocampus than H+
• the amygdala plays an important role in

  • fear conditioning
  • emotional processing

  > Has bidirectional connections

  with hippocampus
• two major glutamate receptors

  1. AMPA
  2. NMDA
• NMDA:

  • occupied by magnesium ION
  • acts as a coincidence detector
• how is the NMDA receptor activated?

  1. glutamate binds tothe binding site

  2. post synaptic terminal is already depolarized
• what are the two primary functions of the LTM?

  1. retention of memories for specific episodes that we have experienced

  2. the extraction from life experiences of general patterns about how the world works
• Animal used in classical conditioning studies

  • Aplysia californica
• Eric Kandel: '“When an axon of cell A is near enough to excite a cell B and repeatedly or persistently takes part in firing it, some growth process or metabolic change takes place in one or both cells such that A’s efficiency, as one of the cells firing B, is increased.”'
• Classical Conditioning


  • Learning process where a neutral stimulus becomes associated with a meaningful stimulus to elicit a specific response
• Cognitive Neuroscience


  • Study of the neural mechanisms underlying cognition
• Hebbian learning

  Neurons that fire together, wire together. Persistent activity causes a long-lasting change in one or both neurons, either in dendrite structure or intracellular machinery
• Hebbian learning is based on the principle that neurons that fire together, wire together
• Synaptic plasticity involves changes in the quantity of neurotransmitters released into a synapse and changes in how effectively cells respond to those neurotransmitters
• Hebb rule


  When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth or metabolic change takes place in both cells such that A’s efficiency, as one of the cells firing B, is increased
• Difference between non-associative and associative learning
• Some spike amplitudes have been attenuated due to the limited frequency response of the recording
• Synaptic plasticity involves changes in the quantity of neurotransmitters released into a synapse and changes in how effectively cells respond to those neurotransmitters
• Classical conditioning modeling with 3 neurons and Hebb’s rule

  1. Increase the strength of the synapses by a value Δw = 0.1 if a presynaptic firing is paired with a postsynaptic firing

  2. Before conditioning: The neutral stimulus (bell) does not activate the postsynaptic neuron EPSP: If h ≥ 0.3 the neuron will fire

  3. After 3 pairings the bell can activate the neuron by itself
• Short term plasticity involves rapid changes in the strength of EPSP that do not persist longer than a second
• Hebb rule: 'When an axon of cell A is near enough to excite cell B and repeatedly or persistently takes part in firing it, some growth or metabolic change takes place in both cells such that A’s efficiency, as one of the cells firing B, is increased.’ (Hebb, 1949)'
• Hebb rule

  • Principles: locality and joint activity
  • Some problems: Can a connection be weakened as well?
  • What is the critical time interval for learning?
  • Can weights become infinitely large?
  • Should we take the existing connection strength into account?
• Long term potentiation (LTP) was discovered in 1966 by Timothy Bliss & Terje Lømo
• Long term plasticity in CA1 (hippocampus)

  • NMDA receptor-Dependent LTP (Bi & Poo, Journal of Neuroscience 1998)
  • Spike time dependent plasticity (STDP) Testing protocol (from: Gerstner, Kistler, Naud and Paninski, Neuronal Dynamics, Cambridge University Press, 2014)
  • Synaptic tag and capture
  • Size of a dendritic spine increases after stimulation (Yagishita et al., Science, 2014)