title: Simulated GABA synaptic input and L-type calcium channels form functional microdomains in hypothalamic gonadotropin-releasing hormone neurons.
abstract: Hypothalamic gonadotropin-releasing hormone (GnRH) neurons integrate the multiple internal and external cues that regulate sexual reproduction. In contrast to other neurons that exhibit extensive dendritic arbors, GnRH neurons usually have a single dendrite with relatively little branching. This largely precludes the integration strategy in which a single dendritic branch serves as a unit of integration. In the present study, we identify a gradient in L-type calcium channels in dendrites of mouse GnRH neurons and its interaction with GABAergic and glutamatergic inputs. Higher levels of L-type calcium channels are in somata/proximal dendrites (i.e., 0-26 μm) and distal dendrites (∼130 μm dendrite length), but intervening midlengths of dendrite (∼27-130 μm) have reduced L-type calcium channels. Using uncaging of GABA, there is a decreasing GABAergic influence along the dendrite and the impact of GABA(A) receptors is dependent on activation of L-type calcium channels. This results in amplification of proximal GABAergic signals and attenuation of distal dendritic signals. Most interestingly, the intervening dendritic regions create a filter through which only relatively high-amplitude, low-frequency GABAergic signaling to dendrites elicits action potentials. The findings of the present study suggest that GnRH dendrites adopt an integration strategy whereby segments of single nonbranching GnRH dendrites create functional microdomains and thus serve as units of integration.
authors: Department of Biology and Neurosciences Institute, University of Texas, San Antonio, San Antonio, Texas 78249, USA.
authors: Peter J
authors: PJ
authors: Hemond
authors: Michael P
authors: MP
authors: O'Boyle
authors: Carson B
authors: CB
authors: Roberts
authors: Alfonso
authors: A
authors: Delgado-Reyes
authors: Zoe
authors: Z
authors: Hemond
authors: Kelly J
authors: KJ
authors: Suter
mesh_terms: D000818:Animals; D001703:Biophysics; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007031:Hypothalamus / Q000166:cytology*; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D021962:Membrane Microdomains; D051379:Mice; D008822:Mice, Transgenic; D018613:Microscopy, Confocal; D008954:Models, Biological; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009553:Nimodipine / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D049452:Green Fluorescent Proteins; D007987:Gonadotropin-Releasing Hormone; D005680:gamma-Aminobutyric Acid; D009553:Nimodipine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C013411:biocytin; D008239:Lysine