Simulated GABA Synaptic Input and L-Type Calcium Channels Form Functional Microdomains in Hypothalamic Gonadotropin-Releasing Hormone Neurons

Abstract

Hypothalamic gonadotropin releasing-hormone neurons integrate the multiple internal and external cues that regulate sexual reproduction. In contrast to other neurons which exhibit extensive dendritic arbors, GnRH neurons usually have a single dendrite with relatively little branching. This largely precludes the integration strategy where 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 mid-lengths 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 non-branching GnRH dendrites create functional microdomains and thus serve as units of integration.

Physiology of the Adult Gonadotropin-Releasing Hormone Neuronal Network

“…58,112 The other channel contributing to the AHP in GnRH neurons is an unusual, molecularly uncharacterized, calcium-activated potassium channel that is antagonized by UCL2077 (Figure 11.4). 58,118 Together these studies suggest that a simple "core model" for burst firing in GnRH neurons could result from: (1) initiation of an action potential; (2) activation of the ADP to start the burst; (3) activation of the SK component of the AHP to terminate the burst; and (4) activation of the UCL component of the AHP to determine when the next burst will occur ( Figure 11.4(C)). 58 Intracellular calcium within the GnRH neuron soma acts to coordinate several of the ion channels involved in bursting.…”

Differential Gene Expression in Gonadotropin-Releasing Hormone Neurons of Male and Metestrous Female Mice

“…In hypothalamic GnRH neurons, high-voltage-activated Ca currents pass through multiple (L-, N-, P-, Q- and R-type) Ca 2+ channels [87,88]. Though L-type calcium channels are essential for the firing activity of GnRH neurons, enhancing GABA A receptor-mediated signaling [89], the function of R-type Ca 2+ channel as a major current component is inevitable in Ca 2+ -dependent GnRH release [90]. We have shown that the expression of voltage-dependent R-type calcium channels is gender specific: the alpha-1e (Cacna1e) , beta-1 (Cacnb1) and gamma-5 (Cacng5) subunits are expressed at higher levels in males.…”

A unified model for two modes of bursting in GnRH neurons

“…The value of α was determined by Eq. (7c), where F is Faraday’s constant, the factor 2 is the valence of the Ca 2+ cation, β =10 6 is a scaling factor that ensures the concentration is in μM, and V cyt = 2.8 pL is the volume of the somatic compartment, estimated by digitizing a confocal image of a representative GnRH neuron (Hemond et al 2012). The estimation of V cyt was obtained by fitting the 2D coordinates of the soma to an ellipse and calculating the volume of the resulting ellipsoid by setting the length of the undetermined axis equal to that of ellipse’s minor axis.…”