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Keywords:

  • bistability;
  • CAN current;
  • computational modelling;
  • slow afterdepolarization;
  • transient receptor potential

Abstract

In several regions of the nervous system, neurons display bi- or multistable intrinsic properties. Such stable states may be subthreshold and long-lasting, and can appear as a sustained afterdepolarization. In hippocampal CA1 pyramidal neurons, small-amplitude (1 mV) long-lasting (seconds) afterdepolarizations have been reported and are thought to depend on calcium-activated nonselective (CAN) currents recently identified as transient receptor potential (TRP) channels. Continuing our previous experimental and computational work on synaptically metabotropic glutamate receptor (mGluR)-activated TRP currents, we here explore small-amplitude long-lasting depolarizations in a detailed multicompartmental model of a CA1 pyramidal neuron. We confirm a previous hypothesis suggesting that the depolarization results from an interplay of TRP and voltage-gated calcium channels, and contribute to the understanding of the depolarization in several ways. Specifically, we show that: (i) the long-lasting depolarization may be intrinsically stable to weak excitatory and inhibitory input, (ii) the phenomenon is essentially located in distal apical dendrites, (iii) induction is facilitated if simultaneous input arrives at several dendritic branches, and if calcium- and/or mGluR-evoked signals undergo summation, suggesting that both spatial and temporal synaptic summation might be required for the depolarization to occur and (iv) we also show that the integration of inputs to oblique dendrites is strongly modulated by the presence of small-amplitude long-lasting depolarizations in distal tuft dendrites. To conclude, we suggest that small-amplitude long-lasting dendritic depolarizations may contribute to sustaining neural information during behavioural tasks in cases where information is separated in time, as in trace conditioning and delay tasks.