PT  - JOURNAL ARTICLE
AU  - Kiho Lee
AU  - Wen Duan
AU  - James Sneyd
AU  - Allan E. Herbison
TI  - Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons
AID  - 10.1523/JNEUROSCI.6156-09.2010
DP  - 2010 May 05
TA  - The Journal of Neuroscience
PG  - 6214--6224
VI  - 30
IP  - 18
4099  - http://www.jneurosci.org/content/30/18/6214.short
4100  - http://www.jneurosci.org/content/30/18/6214.full
SO  - J. Neurosci.2010 May 05; 30
AB  - Gonadotropin-releasing hormone (GnRH) neurons release GnRH in a pulsatile manner to control fertility in all mammals. The mechanisms underlying burst firing in GnRH neurons, thought to contribute to pulsatile GnRH release, are not yet understood. Using minimally invasive, dual electrical–calcium recordings in acute brain slices from GnRH-Pericam transgenic mice, we find that the soma/proximal dendrites of GnRH neurons exhibit long-duration (∼10 s) calcium transients that are perfectly synchronized with their burst firing. These transients were found to be generated by calcium entry through voltage-dependent L-type calcium channels that was amplified by inositol-1,4,5-trisphosphate receptor-dependent store mechanisms. Perforated-patch current- and voltage-clamp electrophysiology coupled with mathematical modeling approaches revealed that these broad calcium transients act to control two slow afterhyperpolarization currents (sIAHP) in GnRH neurons: a quick-activating apamin-sensitive sIAHP that regulates both intraburst and interburst dynamics, and a slow-onset UCL2077-sensitive sIAHP that regulates only interburst dynamics. These observations highlight a unique interplay between electrical activity, calcium dynamics, and multiple calcium-regulated sIAHPs critical for shaping GnRH neuron burst firing.