Dendritic Action Potential Initiation in Hypothalamic Gonadotropin-Releasing Hormone Neurons

Abstract

It is dogma that action potentials are initiated at the soma/axon hillock of neurons. However, dendrites often exhibit conductances necessary for spike generation and represent functionally independent processing compartments within neurons. GnRH neurons provide an interesting neuronal phenotype with simple, relatively unbranched, unipolar or bipolar dendrites of extensive lengths (>1000 microm) covered in spines. These neurons control fertility and must integrate a variety of internal homeostatic and external environmental cues. We used imaging, electrophysiological, and modeling studies to understand how they integrate and process information along dendrites. Simultaneous recordings from distal dendrites and somata of individual GnRH neurons indicate distal dendrites are the primary site of spike initiation in these cells. Compartmental modeling indicates that sites of spike initiation depend upon location of excitatory input and dendrite geometry. Together, these studies demonstrate a novel pattern of spike generation in mammalian neurons and indicate that afferent inputs within distal dendritic microdomains directly initiate action potentials.

Initiation and Propagation of Action Potentials in Gonadotropin-Releasing Hormone Neuron Dendrites

“…Second, the affinity of the CoroNa Green Na ϩ indicator for Na ϩ is low (K d , ϳ80 mM), thus making it difficult to detect very small change in intracellular Na ϩ . The first study to suggest the dendrite as the site of action potential initiation in GnRH neurons also showed through immunohistochemistry that the dendrites of these neurons express voltage-gated Na ϩ channels (Roberts et al, 2008). That study also generated a morphologically based computer model of a GnRH neuron soma and dendrite.…”

“…The initial 150 m of the dendrite have a high sodium channel density It has previously been shown that GnRH neurons express Na ϩ channels on their dendrites (Roberts et al, 2008); however, that immunohistochemistry was not sensitive enough to detect changes in channel density at different points along the dendrite. An alternative method to estimate the relative Na ϩ channel density is to perform intracellular Na ϩ imaging with Na ϩ -sensitive dyes (Meier et al, 2006;Kole et al, 2008;Fleidervish et al, 2010).…”

“…While the long thin processes emanating from the cell body of most GnRH neurons possess spines and have a dendritic morphology (Jennes et al, 1985;Wray and Hoffman, 1986;Campbell et al, 2005Campbell et al, , 2009Cottrell et al, 2006), the origin of the GnRH neuron axon remains undetermined. Recent evidence, however, has suggested that the dendrite may be the site of action potential initiation in these neurons (Roberts et al, 2008).…”

“…In the vast majority of neurons studied, the action potential is first initiated in the axon initial segment, as this region of the neuron has both a hyperpolarized shift in the activation voltage of Na ϩ channels and the highest density of voltage-gated Na ϩ channels (Colbert and Pan, 2002;Kole et al, 2008;Hu et al, 2009;Fleidervish et al, 2010). Interestingly, dual recordings from the soma and dendrite of GnRH neurons suggest that some GnRH neurons may initiate action potentials first in their dendrite (Roberts et al, 2008). It is currently unclear how common this dendritic initiation of spiking is.…”

A simple integrative electrophysiological model of bursting GnRH neurons

“…The model should be able to approximately reproduce the shape of action potentials (APs), and excitability properties observed in GnRH neurons originating from hypothalamic slices Chu & Moenter, 2006;Csercsik et al, 2010). Furthermore, the model should be able to reproduce dendritic AP generation (Roberts, Campbell, et al, 2008). 2.…”