海馬の神経発火パターン

タイトル: Interleaved single and bursting spiking resonance in neurons

概要: Under in vivo conditions, CA1 pyramidal cells from the hippocampus display transitions from single spikes to bursts. It is believed that subthreshold hyperpolarization and depolarization, also known as down and up-states, play a pivotal role in these transitions. Nevertheless, a central impediment to correlating suprathreshold (spiking) and subthreshold activity has been the technical difficulties of this type of recordings, even with widely used calcium imaging or multielectrode recordings. Recent work using voltage imaging with genetically encoded voltage indicators has been able to correlate spiking patterns with subthreshold activity in a variety of CA1 neurons, and recent computational models have been able to capture these transitions. In this work, we used a computational model of a CA1 pyramidal cell to investigate the role of intrinsic conductances and oscillatory patterns in generating down and up-states and their modulation in the transition from single spiking to bursting. Specifically, the emergence of distinct spiking resonances between these two spiking modes that share the same voltage traces in the presence of theta or gamma oscillatory inputs, a phenomenon we call interleaved single and bursting spiking resonance. We noticed that these resonances do not necessarily overlap in frequency or amplitude, underscoring their relevance for providing flexibility to neural processing. We studied the conductance values of three current types that are thought to be critical for the bursting behavior: persistent sodium current (INaP) and its conductance GNaP, delayed rectifier potassium (IKDR) and its conductance GKDR, and hyperpolarization-activated current (Ih) and its conductance Gh. We conclude that the intricate interplay of ionic currents significantly influences the neuronal firing patterns, transitioning from single to burst firing during sustained depolarization. Specifically, the intermediate levels of GNaP and GKDR facilitate spiking resonance at gamma frequency inputs. The resonance characteristics vary between single and burst firing modes, each displaying distinct amplitudes and resonant frequencies. Furthermore, low GNaP and high GKDR values lock bursting to theta frequencies, while high GNaP and low GKDR values lock single spiking to gamma frequencies. Lastly, the duration of quiet intervals plays a crucial role in determining the likelihood of transitioning to either bursting or single spiking modes. We confirmed that the same features were present in previously recorded in vivo voltage-imaging data. Understanding these dynamics provides valuable insights into the fundamental mechanisms underlying neuronal excitability under in vivo conditions. Author summarySince discovering that neurons in the hippocampus can encode spatial position through phase precession, many experiments have explored how specific theta and gamma oscillations influence location specificity in the brain. However, the individual neuronal properties and dynamics behind these behaviors are still being uncovered. Previously, we found that stereotypical bursting and single-spike firing in pyramidal neurons are linked to these oscillations and further associated with an animal entering or leaving a place field. Advances in voltage-imaging techniques have enabled us to assess these properties more precisely. Our study shows that different frequencies can independently trigger these stereotypical spikes, demonstrating a complex pattern where the same cell can be double-coded: a phenomenon we called interleaved resonance. Additionally, we found that this coding can be modulated by persistent sodium and delayed-rectifier potassium currents. Moreover, these neurons are more likely to burst following long periods of silence. These findings provide new insights into the mechanisms underlying neural coding in the hippocampus and how it relates to behavior.