INTRODUCTION


Being able to acquire and retain salient information about the environment to enable survival is a crucial ability ubiquitous to all organisms. Thus understanding how the brain’s is able to retain lifelong memories while simultaneously remaining plastic to new information is fundamental to understanding how the brain works. Research into the neurophysiological basis of learning and memory has shown that in addition to synaptic plasticity, the brain can also be modified at the neuronal and global level. Considered to be the basic structural and functional unit of the central nervous system, the synapse can be strengthened or weakened in an activity-dependent manner in long-term potentiation (LTP) and depression (LTD), respectively. Changes in the probability of neurotransmitter release from the pre-synaptic terminal and the density of glutamate receptors and dendritic spines in the post-synaptic terminal have all been implicated in modulating the strength of transmission at a synapse. At the neuronal level, intrinsic plasticity, which refers to the neuron's ability to adapting its intrinsic propensity to generate action potentials, has been shown to occur in a learning-dependent manner. Modulation of the neuron's membrane excitability directly contributes to the likelihood of NMDA receptor activation and induction of synaptic plasticity. Finally, metaplasticity refers to the brain's ability to reset the LTP and LTD induction thresholds globally after a period of stimulation. This prevents previously potentiated synapses from being further excited and reaching saturation, or depressed synapses from being driven into extinction. By maintaining neurons in a dynamic range of activity, metaplasticity ensures that the brain is continually susceptible to plasticity and that learning can always occur. Thus, an understanding of how plasticity at these three levels changes the brain in an experience-dependent manner is crucial to elucidating the neurophysiological basis of learning and memory.


  • Animal models and learning paradigms(Jing Lu)
    • Model Circuits and behaviours in Animal models
      • Invertebrate models
        • Gastropod Mollusks
          • Aplysia Gill-Siphon Defensive Withdrawal Reflex
          • Lymnaea Breathing Behaviour
        • Drosophila
      • Vertebrate models
        • Rodents
        • Primates
    • Learning paradigms in common animal model
      • Associative learning in Mollusks
        • Classical conditioning
        • Operant conditioning
      • Hippocampal-dependent (Spatial)
      • Hippocampal-independent (Non-spatial)

  • Presynaptic mechanisms of synaptic plasticity (Nancy Dong)
    • Mossy fibre LTP
      • Activations of presynaptic metabotropic glutamate receptors and kainate receptors
      • Increased release probability through cAMP/PKA-dependent modification of active zone proteins
      • Working memory and pattern recognition
    • Endocannabinoid LTD
      • Activity-dependent endocannabinoid mobilization and retrograde signalling
      • CB1 receptor-dependent modification of presynaptic ion channels and release machinery
      • Extinction learning and addiction


  • Metaplasticity (Xinuo Gao)
    • Research development
      • Discovery of “metaplasticity” and its initial research
      • Experimental Evidence
    • Mechanisms
      • Activity-Dependent Mechanism
        • Changes in NMDA Receptors
        • Effects of Ca2+
        • Activation of PKC – Increase in PKMzeta
    • Clinical implications and treatments
      • Neuropsychiatric Disorders
        • Relation to metaplasticity
        • Treatments
      • Cocaine-induced metaplasticity
        • N-acetylcystein functions
        • Possible treatments

  • Intrinsic plasticity (Mihai Chelaru)
    • Intrinsic Plasticity
      • Defining Features of Non-Synaptic plasticity
    • Electrophysiological Markers of Intrinsic Plasticity
      • Changes in Spike Threshold
      • Modulation of Input Resistance
      • Increased Cell Excitability
      • Reduced After-Hyperpolarization
    • Animal Conditioning Paradigms of Intrinsic Plasticity
      • Classical Conditioning Paradigms
      • Operant Conditioning Paradigms
      • Electrophysiological recording from tissue slices
    • Molecular Substrates of Intrinsic Plasticity
      • Modulation of Persistent Ion Currents



References:
Citri, A. & Malenka, R.C. Synaptic plasticity: multiple forms, functions, and mechanisms. Nature. (2008) 33: 18-41
Daoudal, G. & Debanne, D. Long-Term Plasticity of Intrinsic Excitability: Learning Rules and Mechanisms. Learn Mem. (2003) 10: 456-465