Abstract
In area CA1 of the hippocampus, the selection of place cells to represent a new environment is biased towards neurons with higher excitability. However, different environments are represented by orthogonal cell ensembles, suggesting that regulatory mechanisms exist. Activity-dependent plasticity of intrinsic excitability, as observed in vitro, is an attractive candidate. Here, using whole-cell patch-clamp recordings of CA1 pyramidal neurons in anesthetized rats, we have examined how inducing theta-bursts of action potentials affects their intrinsic excitability over time. We observed a long-lasting, homeostatic depression of intrinsic excitability which commenced within minutes, and, in contrast to in vitro observations, was not mediated by dendritic Ih. Instead, it was attenuated by the Kv1.1 channel blocker dendrotoxin K, suggesting an axonal origin. Analysis of place cells' out-of-field firing in mice navigating in virtual reality further revealed an experience-dependent reduction consistent with decreased excitability. We propose that this mechanism could reduce memory interference.
Highlights
The contribution of intrinsic excitability to learning has often been overlooked in favor of synaptic mechanisms (Daoudal and Debanne, 2003; Zhang and Linden, 2003), but recent evidence indicates that it plays an important role in memory allocation processes and the creation of engrams (Josselyn and Frankland, 2018; Titley et al, 2017; Lisman et al, 2018)
Theta burst firing induces a homeostatic decrease in intrinsic excitability of CA1 pyramidal neurons in vivo
Bias towards reduced excitability of place cells during virtual spatial navigation Our results demonstrate that action potential firing can induce a decrease in the intrinsic excitability of CA1 pyramidal neurons, but the question remains as to whether this plasticity affects coding in
Summary
The contribution of intrinsic excitability to learning has often been overlooked in favor of synaptic mechanisms (Daoudal and Debanne, 2003; Zhang and Linden, 2003), but recent evidence indicates that it plays an important role in memory allocation processes and the creation of engrams (Josselyn and Frankland, 2018; Titley et al, 2017; Lisman et al, 2018). That high frequency bursts of action potentials alone can induce a homeostatic decrease in the global excitability of CA1 pyramidal neurons (Fan et al, 2005; Narayanan and Johnston, 2007) Such global change in excitability could be relevant to regulate the allocation process as it allows cells to tune their excitability based on their involvement in coding, without disrupting information contained within the synapses. Mechanistically our effect was independent of Ih, and instead our findings implicate an increase in ID carried by Kv1.1 channels in the axon initial segment (AIS) This indicates that in vivo, action potential firing can regulate global intrinsic excitability independently of dendritic excitability, which may support the co-existence of synaptic learning and memory allocation processes based on plasticity of intrinsic excitability
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