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.

The activity of hypothalamic GnRH neurons results in the intermittent release of GnRH required for reproductive function. This intermittent neurosecretory activity has been proposed to reflect integration of intrinsic properties of and synaptic input to GnRH neurons. Determining the relative impact of synaptic inputs at different locations on the GnRH neuron is difficult, if not impossible, using only experimental approaches. Thus, we used electrophysiological recordings and neuronal reconstructions to generate computer models of GnRH neurons to examine the effects of synaptic inputs at varying distances from the soma along dendrites. The parameters of the models were adjusted to duplicate measured passive and active electrophysiology of cells from mouse brain slices. Our morphological findings reinforce the emerging picture of a complex dendritic structure of GnRH neurons. Furthermore, analysis of reduced morphology models indicated that this population of cells is unlikely to exhibit low-frequency tonic spiking in the absence of synaptic input. Finally, applying realistic patterns of synaptic input to modeled GnRH neurons indicates that synapses located more than about 30% of the average dendrite length from the soma cannot drive firing at frequencies consistent with neuropeptide release. Thus, processing of synaptic input to dendrites of GnRH neurons is probably more complex than simple summation.

Silicon carbide is a wide-band-gap semiconductor suitable for high-power high-voltage devices and it has excellent properties for use in photoconductive semiconductor switches ͑PCSSs͒. PCSS were fabricated as planar structures on high-resistivity 4H-SiC and tested at dc bias voltages up to 1000 V. The typical maximum photocurrent of the device at 1000 V was about 49.4 A. The average on-state resistance and the ratio of on-state to off-state currents were about 20 ⍀ and 3ϫ10 11 , respectively. Photoconductivity pulse widths for all applied voltages were 8-10 ns. These excellent results are due in part to the removal of the surface damage by high-temperature H 2 etching and surface preparation. Atomic force microscopy images revealed that very good surface morphology, atomic layer flatness, and large step width were achieved.

We report the results of drone lidar survey at a high-elevation archaeological site in the Chachapoyas region of Peruvian Amazonia. Unlike traditional airborne remote sensing, drone lidar produces very high-density measurements at a wide range of scan angles by operating at low altitudes and slow flight speeds. These measurements can resolve near vertical surfaces and novel dimensions of variability in architectural datasets. We show in a case study at Kuelap that the number of detected structures almost exactly matches the number reported from previous ground level surveys, and we use these data to quantify the relative circularity and size frequency distribution of architectural structures. We demonstrate variability in domestic architecture that was obscured in previous models produced using low-resolution remote sensing. Spatial analysis of these attributes produces new hypotheses about the site's construction history and social organization.

The impact of structure in modulating synaptic signals originating in dendrites is widely recognized. In this study, we focused on the impact of dendrite morphology on a local spike generating mechanism which has been implicated in hormone secretion, the after depolarization potential (ADP). Using multi-compartmental models of hypothalamic GnRH neurons, we systematically truncated dendrite length and determined the consequence on ADP amplitude and repetitive firing. Decreasing the length of the dendrite significantly increased the amplitude of the ADP and increased repetitive firing. These effects were observed in dendrites both with and without active conductances suggesting they largely reflect passive characteristics of the dendrite. In order to test the findings of the model, we performed whole-cell recordings in GnRH neurons and elicited ADPs using current injection. During recordings, neurons were filled with biocytin so that we could determine dendritic and total projection (dendrite plus axon) length. Neurons exhibited ADPs and increasing ADP amplitude was associated with decreasing dendrite length, in keeping with the predictions of the models. Thus, despite the relatively simple morphology of the GnRH neuron's dendrite, it can still exert a substantial impact on the final neuronal output.

The impact of the A-type γ-aminobutyric acid (GABA-A) receptor in gonadotropin releasing hormone (GnRH) neurons is controversial. In adult GnRH neurons, the GABA-A receptor conductance has been reported to either hyperpolarize or depolarize GnRH neurons. Regardless of whether GABA is inhibitory or excitatory in GnRH neurons, GABAergic input would be integrated with post-synaptic potentials generated by other synaptic inputs. We used dynamic current clamping and compartmental computer modeling to examine the integration of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamatergic input and GABA-mediated input in both the hyperpolarizing (inhibitory) and depolarizing (excitatory) modes. In both living and model neurons, action potentials were most likely a few ms after a maximum in AMPA conductance coincided with a minimum in inhibitory GABA. Excitatory GABA interacted differently with AMPA, with spikes most likely, in both dynamic clamping of living neurons and in model neurons, when a maximum in AMPA coincided with the decay from peak of a maximum in GABA. Distributing synapses along the dendrite maximized the temporal relationship between AMPA and GABA conductances and therefore, the potential for spiking. Thus, these two dominant neurotransmitters could interact in multiple frames to generate action potentials in GnRH neurons. KeywordsGnRH; synaptic integration; compartmental model; glutamate; GABA; hypothalamus Hypothalamic GnRH neurons form the final pathway for integration of signals regulating reproduction. The control of GnRH neurons has been proposed to reflect both their intrinsic electrical properties and the input they receive from presynaptic neurons (Kusano et al., 1995; reviewed by Lopez et al., 1998). Despite the relatively precise requirements in the timing of GnRH pulses for proper reproductive function (Pohl et al., 1983), GnRH neurons have heterogeneous electrophysiological properties (Sim et al., 2001;Spergel et al., 1999). Moreover, emerging evidence suggests that GnRH neurons may differ in their responses to at Corresponding author: Kelly Suter, University of Texas at San Antonio, 1 UTSA Circle, San Antonio TX, 78249. kelly.suter@utsa.edu. Requested Section Editor: Menahem Segal, Department of Neurobiology, Weizmann Institute of Science (Rehovot, Israel) Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access Author ManuscriptNeuroscience. Author manuscript; available in PMC 2009 July 17. Published in final edited form as:Neuroscience. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manus...

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.

No abstract