Initiation and propagation of a neuronal intracell

Authors: Bradford E Peercy

Publish Date: 2008/03/05

Volume: 25, Issue: 2, Pages: 334-348

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Abstract

The ability to image calcium movement within individual neurons inspires questions of functionality including whether calcium entry into the nucleus is related to genetic regulation for phenomena such as long term potentiation Calcium waves have been initiated in hippocampal pyramidal cells with glutmatergic signals both in the presence and absence of back propagating action potentials BPAPs The dendritic sites of initiation of these calcium waves within about 100 µm of the soma are thought to be localized near oblique junctions Stimulation of synapses on oblique dendrites leads to production of inositol 145trisphosphate IP3 which diffuses to the apical dendrite igniting awaiting IP3 receptors IP3Rs and initiating and propagating catalytic calcium release from the endoplasmic reticulum We construct a reduced mathematical system which accounts for calcium wave initiation and propagation due to elevated IP3 Inhomogeneity in IP3 distribution is responsible for calcium wave initiation versus subthreshold or spatially uniform suprathreshold activation However the likelihood that a calcium wave is initiated does not necessarily increase with more calcium entering from BPAPs For low transient synaptic stimuli timing between IP3 generation and BPAPs is critical for calcium wave initiation We also show that inhomogeneity in IP3R density can account for calcium wave directionality Simulating somatic muscarinic receptor production of IP3 we can account for the critical difference between calcium wave entry into the soma and failure to do soThe author would like to thank Steve Cox for his mentorship while at Rice University where the majority of this work was conducted and acknowledge the funding there under the VIGRE grant NSF DMS 0240058 and the Pfeiffer endowment for postdoctoral training Thanks to Artie Sherman for comments on the manuscript This research was also supported in part by the Intramural Research Program of the NIH NIDDKParameter variation effect on IP3R dynamics a p = 03 µM Varying IP3R density affects the number and stability of steady states For R = 1 the system is monostable and excitable For lower density R = 095 the system is less excitable For even lower density the lower knee of the cnullcline is sufficiently raised to lose excitability not shown For elevated density the system may become bistable or lose stability through saddlenode and Hopf bifurcations and become selfoscillatory not shown b R = 1 Varying IP3 levels has similar affects on the IP3R dynamics however the hnullcline is also slightly affected by variation in pConsequently through manipulation of these parameters either manually by altering receptor density or dynamically with a transient pulse of IP3 these excitable dynamics may be exploited to form or make it more or less likely to form a wave of calcium

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