Spike timing dependent plasticity (STOP) is a mechanism whereby the strength of an activated synapse is modified based on its correlation with postsynaptic action potentials. There is much interest in STOP, as it provides a biological substrate for the postulated Hebbian mechanism of memory, upon which many contemporary experimental and theoretical models of learning are based. Here, we propose to study the intracellular correlate of associative memory. STDP has largely been studied by evoking action potentials with somatic current injections. We will study the mechanisms of STDP elicited by correlated activation of separate synaptic pathways, using electrophysiological whole cell recordings. STDP of a weak synaptic input to the apical dendrites of CA1 pyramidal neurons will be paired with action potentials generated by strong synaptic inputs to either proximal apical or basal dendrites. We will then investigate the mechanisms of STDP with calcium imaging and dendritic recordings to directly measure the dendritic events that mediate STDP with synaptic stimuli. This study will investigate the underlying mechanisms of synaptically driven STDP. Relevance: There is a significant body of evidence that plasticity an important mechanism in learning, memory, and cognitive function. The proposed studies here will investigate mechanisms of synaptic plasticity for physiological inputs, and how plasticity is modulated. A fundamental understanding of the basic mechanisms of plasticity at the cellular level will ultimately contribute to a better understanding of cognitive function, and facilitate the development off therapeutic treatment of cognitive dysfunctions.
| Hardie, Jason; Spruston, Nelson (2009) Synaptic depolarization is more effective than back-propagating action potentials during induction of associative long-term potentiation in hippocampal pyramidal neurons. J Neurosci 29:3233-41 |
