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

Abstract

Gonadotropin-releasing hormone (GnRH) neurons are the final output neurons in a complex neuronal network that regulates fertility. The morphology of GnRH neuron dendrites is very different to other central neurons in that they are very long, thin, and unbranched. To study the function of these dendrites, we have used Na ϩ and Ca 2ϩ imaging in combination with dual soma and dendrite electrical recordings in brain slices from GnRH-GFP mice. Here, we show that GnRH neurons actively propagate Na ϩ spikes throughout their dendrites. Multisite dendritic recordings confirmed that these spikes were observed in one of the dendrites before the soma in the great majority of neurons tested. Na ϩ imaging experiments revealed that the initial 150 m of dendrite has a higher density of functional Na ϩ channels than more distal regions, suggesting that this region of dendrite is highly excitable and may be the site of spike initiation. Finally, we show that the depolarization from dendritic spikes opens voltage-gated Ca 2ϩ channels giving rise to dendritic Ca 2ϩ transients. Together, these findings suggest that the proximal dendrites of GnRH neurons are highly excitable and are likely to be the site of action potential initiation in these neurons.

Multitasking in Gonadotropin-Releasing Hormone Neuron Dendrites

“…Subsequent work from our laboratory has confirmed this and further determined that these sodium spikes are actively conducted throughout all parts of the dendritic projection. In addition, we have identified a region 50-150 μm down one dendrite as being the spike initiation site [26]. This region of the dendrite also labels for the spike initiation site marker ankyrin G [3] and possesses a high density of functional voltage-gated sodium channels [26].…”

“…In addition, we have identified a region 50-150 μm down one dendrite as being the spike initiation site [26]. This region of the dendrite also labels for the spike initiation site marker ankyrin G [3] and possesses a high density of functional voltage-gated sodium channels [26]. Interestingly, while the entire dendritic projection can actively conduct spikes, there appears to be only one site of spike initiation.…”

“…Neurotransmitter puffs onto the dendron evoke reliable membrane potential changes recorded at the cell body [26]. As expected for passive electrotonic decay of subthreshold potentials, the amplitude of these responses becomes smaller and smaller at greater distances from the recording electrode at the soma.…”

“…It is important to note that glutamate-evoked sodium spikes are initiated at the same spike initiation site regardless of where along the dendron the glutamate receptors are activated. This location of spike initiation is the same as for spontaneously evoked spiking [26]. …”

“…As noted earlier, this region contains the spike initiation site [26] and also has the highest density of synaptic innervation [10]. The synaptic inputs that impinge close to the spike initiation site will be highly effective at controlling action potential firing.…”