Calcium control of triphasic hippocampal STDP

J Comput Neurosci. 2012 Dec;33(3):495-514. doi: 10.1007/s10827-012-0397-5. Epub 2012 May 19.

Abstract

Synaptic plasticity is believed to represent the neural correlate of mammalian learning and memory function. It has been demonstrated that changes in synaptic conductance can be induced by approximately synchronous pairings of pre- and post- synaptic action potentials delivered at low frequencies. It has also been established that NMDAr-dependent calcium influx into dendritic spines represents a critical signal for plasticity induction, and can account for this spike-timing dependent plasticity (STDP) as well as experimental data obtained using other stimulation protocols. However, subsequent empirical studies have delineated a more complex relationship between spike-timing, firing rate, stimulus duration and post-synaptic bursting in dictating changes in the conductance of hippocampal excitatory synapses. Here, we present a detailed biophysical model of single dendritic spines on a CA1 pyramidal neuron, describe the NMDAr-dependent calcium influx generated by different stimulation protocols, and construct a parsimonious model of calcium driven kinase and phosphatase dynamics that dictate the probability of stochastic transitions between binary synaptic weight states in a Markov model. We subsequently demonstrate that this approach can account for a range of empirical observations regarding the dynamics of synaptic plasticity induced by different stimulation protocols, under regimes of pharmacological blockade and metaplasticity. Finally, we highlight the strengths and weaknesses of this parsimonious, unified computational synaptic plasticity model, discuss differences between the properties of cortical and hippocampal plasticity highlighted by the experimental literature, and the manner in which further empirical and theoretical research might elucidate the cellular basis of mammalian learning and memory function.

MeSH terms

  • Action Potentials
  • Algorithms
  • Biophysics
  • CA1 Region, Hippocampal / cytology
  • CA1 Region, Hippocampal / physiology
  • Calcium / physiology*
  • Calcium Signaling / physiology
  • Computer Simulation
  • Dendritic Spines / physiology
  • Electrophysiological Phenomena / physiology
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Humans
  • Kinetics
  • Markov Chains
  • Models, Neurological
  • Neural Conduction / physiology
  • Neuronal Plasticity / physiology*
  • Neurons / physiology*
  • Receptors, AMPA / physiology
  • Receptors, N-Methyl-D-Aspartate / physiology
  • Stochastic Processes

Substances

  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • Calcium