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Golomb et al., (2006). Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study.

March 2012, model of the month by Youwei Zheng
Original model: BIOMD0000000118, BIOMD0000000119

The intrinsic firing modes of adult CA1 pyramidal cells vary from regular firing to rhythmic bursting, depending on the ionic composition of the extracellular environment. Given that the bursting model plays important roles in electrical signaling and induction of long-term synaptic plasticity, it is important to understand how constitution and environment interact in regulating this mode. A larger proportion of evidences have indicated that the propensity of a neuron to burst, depends not only on its constitution but also on this environment. However, most theoretical studies focused only on the constitution.

Golomb et al [1, BIOMD0000000118, BIOMD0000000119] studied the mechanism by which changes in the environment, the extracellular concentrations of Ca2+ modulate transitions between regular firing and bursting in adult CA1 pyramidal cells by combining electrophysiological, computational, and analysis techniques.

Figure 1

Figure 1: The effect of lowering [Ca2+]0 on the firing mode of a truncated CA1 pyramidal cell in normal artificial cerebrospinal fluid. Figure taken from [1].

Figure 2

Figure 2: Comparison of spontaneous rhythmic bursting in a truncated CA1 pyramidal cell and in the neuron model. Figure taken from [1].

Experimentally, the authors examined 24 truncated neurons and demonstrated that lowering the concentration of Ca2+ from 2 to nominally 0 mM caused a progressive increase in the spike afterdepolarization Figure 1.

Theoretically, the authors represented a somatic, single-compartment model by coupled differential equations according to the Hodgkin-Huxley-type scheme. The model was constructed in two stages. In the first stage [BIOMD0000000118], only the ionic currents that are involved in firing dynamics in zero [Ca2+]0, were introduced (see equation 1). In the second stage non-zero[Ca2+]0 [BIOMD0000000119], the model includes all the currents that belong to the first model, and in addition, incorporate three calcium-dependent currents (see equation 2). In the condition of zero [Ca2+]0, a comparison of spontaneous rhythmic bursting in a truncated CA1 pyramidal cell and in the model neuron is shown in Figure 2

Equation 1 Equation 2

They then discovered that CA1 pyramidal cells perfused with calcium free artificial cerebrospinal fluid (ACSF) display a diversity of firing pattern, ranging from regular firing to spontaneous rhythmic bursting, which was shown also in the previous literature [2, 3]. Therefore, the hypothesis that a variation in the density of persistent Na+ channels may generate such diversity was tested and it was concluded that increasing gNaP enhances burstiness in the model neuron Figure 3.

In addition, the paper shows that, using fast-slow analysis and bifurcation theory, the M-type K+ current (IM) allows bursting by shifting neuronal behavior between a slient and a tonically active state provided the kinetics of the spike generating currents are sufficiently, although not extremely fast.

In conclusion, the model accounts, with different parameter sets, for the diversity of firing patterns observed in both zero and non-zero [Ca2+]0. Given the data and analysis, it was suggested that bursting in CA1 pyramidal cells can be explained by a single compartment "square bursting" mechanism with one slow variable.

Figure 3

Figure 3: Variant firing patterns of the neuron model for zero [Ca2+]o and various values of gNaP. Parameter values used for generating this figure are Iapp = 0.66; gNaP = 0.0, 0.08, 0.18, 0.3. Figures are obtained by simulating BIOMD0000000118.

Bibliographic References

  1. Golomb D , Yue C , Yaari Y. Contribution of persistent Na+ current and M-type K+ current to somatic bursting in CA1 pyramidal cells: combined experimental and modeling study. J. Neurophysiol. Oct; 96(4);1912-26, 2006. [CiteXplore]
  2. Azouz R , Jensen MS , Yaari Y. Ionic basis of spike after-depolarization and burst generation in adult rat hippocampal CA1 pyramidal cells. J. Physiol. (Lond.) Apr; 492(1);211-23, 1996. [CiteXplore]
  3. Su H , Alroy G , Kirson ED , Yaari Y. Extracellular calcium modulates persistent sodium current-dependent burst-firing in hippocampal pyramidal neurons. J. Neurosci. Jun; 21(12):4173-82, 2001. [CiteXplore]