A model of a CA3 hippocampal pyramidal neuron incorporating voltage-clamp data on intrinsic conductances

Abstract

1. We have developed a 19-compartment cable model of a guinea pig CA3 pyramidal neuron. Each compartment is allowed to contain six active ionic conductances: gNa, gCa, gK(DR) (where DR stands for delayed rectifier), gK(A), gK(AHP), and gK(C). THe conductance gCa is of the high-voltage activated type. The model kinetics for the first five of these conductances incorporate voltage-clamp data obtained from isolated hippocampal pyramidal neurons. The kinetics of gK(C) are based on data from bullfrog sympathetic neurons. The time constant for decay of submembrane calcium derives from optical imaging of Ca signals in Purkinje cell dendrites. 2. To construct the model from available voltage-clamp data, we first reproduced current-clamp records from a model isolated neuron (soma plus proximal dendrites). We next assumed that ionic channel kinetics in the dendrites were the same as in the soma. In accord with dendritic recordings and calcium-imaging data, we also assumed that significant gCa occurs in dendrites. We then attached sections of basilar and apical dendritic cable. By trial and error, we found a distribution (not necessarily unique) of ionic conductance densities that was consistent with current-clamp records from the soma and dendrites of whole neurons and from isolated apical dendrites. 3. The resulting model reproduces the Ca(2+)-dependent spike depolarizing afterpotential (DAP) recorded after a stimulus subthreshold for burst elicitation. 4. The model also reproduces the behavior of CA3 pyramidal neurons injected with increasing somatic depolarizing currents: low-frequency (0.3-1.0 Hz) rhythmic bursting for small currents, with burst frequency increasing with current magnitude; then more irregular bursts followed by afterhyperpolarizations (AHPs) interspersed with brief bursts without AHPs; and finally, rhythmic action potentials without bursts. 5. The model predicts the existence of still another firing pattern during tonic depolarizing dendritic stimulation: brief bursts at less than 1 to approximately 12 Hz, a pattern not observed during somatic stimulation. These bursts correspond to rhythmic dendritic calcium spikes. 6. The model CA3 pyramidal neuron can be made to resemble functionally a CA1 pyramidal neuron by increasing gK(DR) and decreasing dendritic gCa and gK(C). Specifically, after these alterations, tonic depolarization of the soma leads to adapting repetitive firing, whereas stimulation of the distal dendrites leads to bursting. 7. A critical set of parameters concerns the regulation of the pool of intracellular [Ca2+] that interacts with membrane channels (gK(C) and gK(AHP)), particularly in the dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Inositol Triphosphate-Mediated Ca2+Signals Direct Purinergic P2Y Receptor Regulation of Neuronal Ion Channels

“…Four voltage-gated and two Ca 2ϩ -dependent conductances (available for download through ModelDB at http:// senselab.med.yale.edu) were inserted into the model. A fast voltage-gated Na ϩ conductance (nahh.mod) (Traub et al, 1991) was inserted with a density of 5 mS/cm 2 . Threshold was adjusted by shifting the voltage dependence of the forward and backward activation rate constants by ϩ20 and ϩ10 mV, respectively.…”

The Relationship Between Synchronization Among Neuronal Populations and Their Mean Activity Levels

“…Conductances were implicitly normalized by a leak membrane conductance, so that they were adimensional. The implementation of NMDA channel, was based on Traub, Wong, Miles, & Michelson, (1991):…”

Topological and phenomenological classification of bursting oscillations

“…Plant and Kim, 1976;Canavier et al, 1991;Bertram, 1993;Smolen and Keizer, 1992;Guckenheimer et al, 1994;Rinzel and Troy, 1982;Traub et al, 1991;Wang et al, 1991) and a systematic mathematical analysis of one such model was first performed by Rinzel (1985). In this analysis the system variables were classified as either "fast", if the variable changed significantly over the duration of a single spike, or "slow", if significant change occurred only over the duration of the burst.…”