Synaptic control of spike timing and spike timing-dependent plasticity during theta frequency oscillation in hippocampal CA1 pyramidal neurons

• Main Author: Kwag, Jeehyun
• Published: University of Oxford 2007
• Subjects: 612.8
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.487275

Spike timing during oscillation has been suggested to play an important role in hippocampal processing. However, how the hippocampal network and the individual neurons interact to precisely control spike timing when they receive synaptic inputs from two major excitatory input pathways - Schaffer collateral and perforant path - during natural network oscillation is yet unknown. Investigation of spike timing control mechanism would shed light on how the local STDP learning rule could be influenced by different cortical inputs during theta oscillation. Here I used whole-cell path-clamp recording of CAl pyramidal neurons in vitro and dynamic clamp to simulate in vivo-like theta frequency oscillation at the soma to characterise the spike timing responses of CAl pyramidal neurons to Schaffer collateral and perforant path inputs during theta oscillation and present them as phase response curves (PRCs), Analysis of PRCs revealed that postsynaptic spike times could not only be advanced but also be delayed depending on the timing of excitatory inputs relative to the oscillation. Such control of spike timing during theta oscillation was dependent on the synaptic weight of the input and the frequency of the oscillation. Ih and GABAB receptor-mediated inhibition were identified as an intrinsic and synaptic mechanism, respectively, underlying spike time delay during oscillation. Activation of both Ih and GABAi3 receptor-mediated inhibition by perforant path stimulation contributed to greater spike time delay compared to that with Schaf.:fer collateral input stimulation which was only mediated by Ih. Such different spike timing characteristics were important in STDP induction at the Schaffer collateral-CAl pyramidal cell synapse, Depending on the timing of the perforant path activation during theta oscillation, perforant path input could control the timing of the postsynaptic spike during STDP induction which could reverse the sign of the synaptic modification, Thus, during natural network oscillation with multiple synaptic inputs active, timing of the heterosynaptic inputs from entorhinal cortex to the hippocampus could control the outcome of the homosynaptic plasticity in the CAL These results may have implications for how the external information could be encoded and stored in the hippocampal network.