The subfornical organ and organum vasculosum of the lamina terminalis: Critical roles in cardiovascular regulation and the control of fluid balance.

In this chapter, we review the extensive literature describing the roles of the subfornical organ (SFO), the organum vasculosum of the terminalis (OVLT), and the median preoptic nucleus (MnPO), comprising the lamina terminalis, in cardiovascular regulation and the control of fluid balance. We present this information in the context of both historical and technological developments which can effectively be overlaid upon each other. We describe intrinsic anatomy and connectivity and then discuss early work which described how circulating angiotensin II acts at the SFO to stimulate drinking and increase blood pressure. Extensive studies using direct administration and lesion approaches to highlight the roles of all regions of the lamina terminalis are then discussed. At the cellular level we describe c-Fos and electrophysiological work, which has highlighted an extensive group of circulating hormones which appear to influence the activity of specific neurons in the SFO, OVLT, and MnPO. We highlight optogenetic studies that have begun to unravel the complexities of circuitries underlying physiological outcomes, especially those related to different components of drinking. Finally, we describe the somewhat limited human literature supporting conclusions that these structures play similar and potentially important roles in human physiology.

Genome-Wide Association Study Identifies Single Nucleotide Polymorphism Markers Associated with Mycelial Growth (at 15, 20, and 25°C), Mefenoxam Resistance, and Mating Type in Phytophthora infestans.

Phenotypic diversity among individuals defines the potential for evolutionary selection in a species. Phytophthora infestans epidemics are generally thought to be favored by moderate to low temperatures, but temperatures in many locations worldwide are expected to rise as a result of global climate change. Thus, we investigated variation among individuals of P. infestans for relative growth at different temperatures. Isolates of P. infestans came from three collections: (i) individual genotypes recently dominant in the United States, (ii) recently collected individuals from Central Mexico, and (iii) progeny of a recent sexual recombination event in the northeastern United States. In general, these isolates had optimal mycelial growth rates at 15 or 20°C. However, two individuals from Central Mexico grew better at higher temperatures than did most others and two individuals grew relatively less at higher temperatures than did most others. The isolates were also assessed for mefenoxam sensitivity and mating type. Each collection contained individuals of diverse sensitivities to mefenoxam and individuals of the A1 and A2 mating type. We then searched for genomic regions associated with phenotypic diversity using genotyping-by-sequencing. We found one single nucleotide polymorphism (SNP) associated with variability in mycelial growth at 20°C, two associated with variability in mycelial growth at 25°C, two associated with sensitivity to mefenoxam, and one associated with mating type. Interestingly, the SNPs associated with mefenoxam sensitivity were found in a gene-sparse region, whereas the SNPs associated with growth at the two temperatures and mating type were found both at more gene-dense regions.

Phylogeography, Population Structure, and Species Delimitation in Rockhopper Penguins (Eudyptes chrysocome and Eudyptes moseleyi).

Rockhopper penguins are delimited as 2 species, the northern rockhopper (Eudyptes moseleyi) and the southern rockhopper (Eudyptes chrysocome), with the latter comprising 2 subspecies, the western rockhopper (Eudyptes chrysocome chrysocome) and the eastern rockhopper (Eudyptes chrysocome filholi). We conducted a phylogeographic study using multilocus data from 114 individuals sampled across 12 colonies from the entire range of the northern/southern rockhopper complex to assess potential population structure, gene flow, and species limits. Bayesian and likelihood methods with nuclear and mitochondrial DNA, including model testing and heuristic approaches, support E. moseleyi and E. chrysocome as distinct species lineages with a divergence time of 0.97 Ma. However, these analyses also indicated the presence of gene flow between these species. Among southern rockhopper subspecies, we found evidence of significant gene flow and heuristic approaches to species delimitation based on the genealogical diversity index failed to delimit them as species. The best-supported population models for the southern rockhoppers were those where E. c. chrysocome and E. c. filholi were combined into a single lineage or 2 lineages with bidirectional gene flow. Additionally, we found that E. c. filholi has the highest effective population size while E. c. chrysocome showed similar effective population size to that of the endangered E. moseleyi. We suggest that the current taxonomic definitions within rockhopper penguins be upheld and that E. chrysocome populations, all found south of the subtropical front, should be treated as a single taxon with distinct management units for E. c. chrysocome and E. c. filholi.

Acute ß-tetrabromoethylcyclohexane (ß-TBECH) treatment inhibits the electrical activity of rat Purkinje neurons.

Brominated flame-retardants are environmentally pervasive and persistent synthetic chemicals, some of which have been demonstrated to disrupt neuroendocrine signaling and electrical activity of neurons. 1,2-dibromo-4-(1,2-dibromoethyl)-cyclohexane (TBECH) lacks the toxicity of other classes of BFRs, however its safety is still questioned, as little is known of its neurological effects. Therefore, we sought to determine if TBECH could acutely alter the electrical activity of Purkinje neurons maintained in vitro. Briefly, cerebella from gestational day 20 rats were dissociated and maintained for up to three weeks in culture. Action potentials of Purkinje neurons were detected by cell-attached patch clamp before, during, and after application of ß-TBECH. ß-TBECH decreased action potential activity in a dose-dependent manner with an apparent EC50 of 396 nM. ß-TBECH did not significantly alter the coefficient of variation, a measure of the regularity of firing, suggesting that the mechanism of ß-TBECH's effects on firing frequency may be independent of Purkinje neuron intracellular calcium handling. Because levels of ß-TBECH in exposed individuals may not approach the EC50, these data suggest that any abnormal neurodevelopment or behavior linked with ß-TBECH exposure may result from endocrinological effects as opposed to direct disruption of electrical activity.

Electrophysiological properties of rat subfornical organ neurons expressing calbindin D28K.

The subfornical organ (SFO) is forebrain sensory circumventricular organ, characterized by lack of a blood-brain barrier. Neurons of the SFO can detect circulating molecules such as peptide hormones and communicate this information to regulatory centers behind the blood-brain barrier, thus playing a critical role in homeostatic processes including regulation of energy balance, hydromineral balance and cardiovascular control. The SFO contains two subregions defined by neuronal expression of molecular markers: the dorsolateral peripheral or shell SFO (sSFO) neurons express calretinin, and the ventromedial core (cSFO) neurons express calbindin D28K. Neurons from these two subregions project to different locations to subserve different roles in homeostatic regulation. It is unknown whether neurons from these two subregions exhibit unique or identifiable electrophysiological properties. This study used a gold nanoparticle-conjugated RNA fluorescent probe on dissociated SFO neuron cultures and patch clamp electrophysiology to characterize the intrinsic electrophysiological properties of cSFO and sSFO neurons. Our studies revealed that neurons originating from the core region exhibited significantly more action potential bursting, while neurons from non-core regions exhibited more tonic firing neurons, albeit at a higher overall frequency. The difference in activity is correlated with a more depolarized resting membrane potential and a higher density of voltage gated Na+ currents.

The transcriptome of the rat subfornical organ is altered in response to early postnatal overnutrition.

Early postnatal overnutrition in humans is associated with long-term negative outcomes including obesity, increased risk of type-II diabetes, and cardiovascular disease. Hypothalamic neurons from rodents exposed to early postnatal overnutrition show altered expression of satiety signals and receptors, and exhibit altered responses to many satiety signals, suggesting a hypothalamic link between early overnutrition and development of these sequelae. Importantly, several hypothalamic nuclei receive information regarding circulating hormones (such as insulin, leptin and ghrelin) from the subfornical organ (SFO), a forebrain sensory circumventricular organ which lacks a blood brain barrier. Previous transcriptomic studies indicate that challenges to energy balance and hydration status stimulate changes in gene expression within the SFO, including genes encoding ion channels and receptors. In order to determine if early postnatal overnutrition also causes changes in SFO gene expression which may be associated with homeostatic dysregulation, we performed whole transcriptome sequencing on SFO tissue from rats raised in small (4 pups), or control (large, 12 pups) litters. Illumina RNA sequencing was performed on SFO tissue from rats raised from small and large litters, and read sequences were aligned to the Rat Rnor_6.0 genome. Control data were further compared to previously published microarray data set for validation. We found statistically significant (p < 0.05) changes in expression of 12 transcripts, three of which have likely roles in neuronal excitability, neurite outgrowth and differentiation, and food intake (Manf, Slc24a4, Cracr2b). Additionally, gene ontology analysis identified a trend among significantly altered transcripts in roles for oxidative stress response. We conclude that the SFO transcriptome is subtly altered by early postnatal overnutrition, and recommend further investigation of the effect of early postnatal overnutrition on SFO physiology and morphology.

Lack of current observed in HEK293 cells expressing NALCN channels.

The sodium leak channel NALCN is poorly understood, but is reported as a Na+-permeable, nonselective cation leak channel which regulates resting membrane potential and electrical excitability. Previous work has indicated that NALCN currents can be stimulated by activation of several G protein coupled receptors, including the M3 muscarinic receptor. We undertook a study using voltage clamp electrophysiology to investigate NALCN currents. We compared currents elicited from untransfected control HEK239 cells in response to M3R agonists muscarine or Oxotremorine M to currents elicited from cells transfected with M3R only or the M3R plus NALCN and cDNA encoding accessory proteins UNC-80 and Src. Currents with similar properties were observed in all three groups of cells in response to muscarine agonists, in similar proportions of cells tested, from all three groups of cells. Our findings do not support previous electrophysiological studies suggesting that heterologously expressed NALCN functions as a Na+ leak channel in HEK293 cells. More research will be required to determine the molecular requirements for successful expression of the NALCN channel.

Phytophthora betacei, a new species within Phytophthora clade 1c causing late blight on Solanum betaceum in Colombia.

Over the past few years, symptoms akin to late blight disease have been reported on a variety of crop plants in South America. Despite the economic importance of these crops, the causal agents of the diseases belonging to the genus Phytophthora have not been completely characterized. In this study, a new Phytophthora species was described in Colombia from tree tomato (Solanum betaceum), a semi-domesticated fruit grown in northern South America. Comprehensive phylogenetic, morphological, population genetic analyses, and infection assays to characterize this new species, were conducted. All data support the description of the new species, Phytophthora betacei sp. nov. Phylogenetic analyses suggest that this new species belongs to clade 1c of the genus Phytophthora and is a close relative of the potato late blight pathogen, P. infestans. Furthermore, it appeared as the sister group of the P. andina strains collected from wild Solanaceae (clonal lineage EC-2). Analyses of morphological and physiological characters as well as host specificity showed high support for the differentiation of these species. Based on these results, a complete description of the new species is provided and the species boundaries within Phytophthora clade 1c in northern South America are discussed.

A simple and inexpensive way to document simple husbandry in animal care facilities using QR code scanning.

Record keeping within research animal care facilities is a key part of the guidelines set forth by national regulatory bodies and mandated by federal laws. Research facilities must maintain records of animal health issues, procedures and usage. Facilities are also required to maintain records regarding regular husbandry such as general animal checks, feeding and watering. The level of record keeping has the potential to generate excessive amounts of paper which must be retained in a fashion as to be accessible. In addition it is preferable not to retain within administrative areas any paper records which may have been in contact with animal rooms. Here, we present a flexible, simple and inexpensive process for the generation and storage of electronic animal husbandry records using smartphone technology over a WiFi or cellular network.

Suppression of planar cell polarity signaling and migration in glioblastoma by Nrdp1-mediated Dvl polyubiquitination.

The lethality of the aggressive brain tumor glioblastoma multiforme (GBM) results in part from its strong propensity to invade surrounding normal brain tissue. Although oncogenic drivers such as epidermal growth factor receptor activation and Phosphatase and Tensin homolog inactivation are thought to promote the motility and invasiveness of GBM cells via phosphatidylinostitol 3-kinase activation, other unexplored mechanisms may also contribute to malignancy. Here we demonstrate that several components of the planar cell polarity (PCP) arm of non-canonical Wnt signaling including VANGL1, VANGL2 and FZD7 are transcriptionally upregulated in glioma and correlate with poorer patient outcome. Knockdown of the core PCP pathway component VANGL1 suppresses the motility of GBM cell lines, pointing to an important mechanistic role for this pathway in glioblastoma malignancy. We further observe that restoration of Nrdp1, a RING finger type E3 ubiquitin ligase whose suppression in GBM also correlates with poor prognosis, reduces GBM cell migration and invasiveness by suppressing PCP signaling. Our observations indicate that Nrdp1 physically interacts with the Vangl1 and Vangl2 proteins to mediate the K63-linked polyubiquitination of the Dishevelled, Egl-10 and Pleckstrin (DEP) domain of the Wnt pathway protein Dishevelled (Dvl). Ubiquitination hinders Dvl binding to phosphatidic acid, an interaction necessary for efficient Dvl recruitment to the plasma membrane upon Wnt stimulation of Fzd receptor and for the propagation of downstream signals. We conclude that the PCP pathway contributes significantly to the motility and hence the invasiveness of GBM cells, and that Nrdp1 acts as a negative regulator of PCP signaling by inhibiting Dvl through a novel polyubiquitination mechanism. We propose that the upregulation of core PCP components, together with the loss of the key negative regulator Nrdp1, act coordinately to promote GBM invasiveness and malignancy.

Thromboelastography in Dogs with Chronic Hepatopathies.

BACKGROUND: The coagulation status of dogs with liver disease is difficult to predict using conventional coagulation testing. HYPOTHESIS/OBJECTIVES: To evaluate thromboelastography (TEG) results and associations with conventional coagulation results and indicators of disease severity and prognosis in dogs with chronic hepatopathies (CH). ANIMALS: Twenty-one client-owned dogs. METHODS: Dogs with CH were prospectively (10 dogs) and retrospectively (11 dogs) enrolled from 2008 to 2014. Kaolin-activated TEG was performed and compared with reference intervals by t-tests or Mann-Whitney tests. Correlation coefficients for TEG results and conventional coagulation and clinicopathologic results were determined. Significance was set at P < .05. RESULTS: Dogs with CH had significant increases in R (5.30 min vs 4.33 min), K (3.77 min vs 2.11 min), and LY30 (4.77% vs 0.68%) and decreased angles (55.3° vs 62.4°). G value defined 9 of 21, 7 of 21, and 5 of 21 dogs as normocoagulable, hypercoagulable, and hypocoagulable, respectively. G and MA were correlated with fibrinogen (r = 0.68, 0.83), prothrombin time (PT; r = -0.51, -0.53), and activated partial thromboplastin time (aPTT; r = -0.50, -0.50). K was correlated with PT (r = 0.75) and protein C activity (r = -0.92). Angle was correlated with aPTT (r = -0.63). Clinical score was correlated with PT (r = 0.60), MA (r = -0.53), and R (r = -0.47). Dogs with hyperfibrinolysis (LY30 > 3.04%; 5 of 21) had significantly higher serum transaminase activities. Dogs with portal hypertension had significantly lower G, MA, and angle and prolonged, K, R, and PT. CONCLUSIONS AND CLINICAL RELEVANCE: Dogs with CH have variable TEG results. Negative prognostic indicators in CH correlate with hypocoagulable parameters on TEG. Hyperfibrinolysis in dogs with CH is associated with high disease activity.

Five Reasons to Consider Phytophthora infestans a Reemerging Pathogen.

Phytophthora infestans has been a named pathogen for well over 150 years and yet it continues to "emerge", with thousands of articles published each year on it and the late blight disease that it causes. This review explores five attributes of this oomycete pathogen that maintain this constant attention. First, the historical tragedy associated with this disease (Irish potato famine) causes many people to be fascinated with the pathogen. Current technology now enables investigators to answer some questions of historical significance. Second, the devastation caused by the pathogen continues to appear in surprising new locations or with surprising new intensity. Third, populations of P. infestans worldwide are in flux, with changes that have major implications to disease management. Fourth, the genomics revolution has enabled investigators to make tremendous progress in terms of understanding the molecular biology (especially the pathogenicity) of P. infestans. Fifth, there remain many compelling unanswered questions.

Differential Susceptibility of 39 Tomato Varieties to Phytophthora infestans Clonal Lineage US-23.

During the summers of 2012 and 2013, 39 tomato (Solanum lycopersicum) lines or varieties were evaluated for resistance to late blight in three separate field trials. In each trial, late blight was caused by field isolates of Phytophthora infestans clonal lineage US-23. Varieties with the late blight resistance genes Ph-1, Ph-2, Ph-3, and Ph-2 + Ph-3 were included, along with several heirloom varieties with grower-reported resistance and varieties with no known resistance. All six varieties with Ph-2 + Ph-3, along with NC25P, which is homozygous for Ph-3 only, showed a high level of resistance. Plum Regal F1, which is heterozygous for Ph-3 only, showed moderate resistance. Legend, the only variety with Ph-2 alone, also showed moderate resistance. Three heirloom varieties, Matt's Wild Cherry, Lemon Drop, and Mr. Stripey, showed a high level of resistance comparable with that of varieties with Ph-2 + Ph-3. New Yorker, possessing Ph-1 only, showed no resistance. Indeterminate varieties had significantly less disease than determinate varieties in two of the three trials. Overall, this study suggests that tomato varieties with both Ph-2 and Ph-3 can be used to effectively manage late blight caused by P. infestans clonal lineage US-23. Varieties possessing only Ph-2, or heterozygous for Ph-3, were better protected than those without any late blight resistance but might still require supplemental fungicide applications, while the variety that was homozygous for Ph-3 was highly resistant. Several heirloom varieties were also highly resistant, and the unknown mechanism of their resistance warrants further research. Finally, the plasticity observed in United States P. infestans populations over the past several decades necessitates continued monitoring for genetic changes within P. infestans that could lead to the breakdown of resistance reported here.

The 2009 Late Blight Pandemic in the Eastern United States - Causes and Results.

The tomato late blight pandemic of 2009 made late blight into a household term in much of the eastern United States. Many home gardeners and many organic producers lost most if not all of their tomato crop, and their experiences were reported in the mainstream press. Some CSAs (Community Supported Agriculture) could not provide tomatoes to their members. In response, many questions emerged: How did it happen? What was unusual about this event compared to previous late blight epidemics? What is the current situation in 2012 and what can be done? It's easiest to answer these questions, and to understand the recent epidemics of late blight, if one knows a bit of the history of the disease and the biology of the causal agent, Phytophthora infestans.

Phenotypic Characterization of Recent Clonal Lineages of Phytophthora infestans in the United States.

Phytophthora infestans, the causal agent of late blight disease, has been reported in the United States and Canada since the mid-nineteenth century. Due to the lack of or very limited sexual reproduction, the populations of P. infestans in the United States are primarily reproducing asexually and, thus, show a simple genetic structure. The emergence of new clonal lineages of P. infestans (US-22, US-23, and US-24) responsible for the late blight epidemics in the northeastern region of the United States in the summers of 2009 and 2010 stimulated an investigation into phenotypic traits associated with these genotypes. Mating type, differences in sensitivity to mefenoxam, differences in pathogenicity on potato and tomato, and differences in rate of germination were studied for clonal lineages US-8, US-22, US-23, and US-24. Both A1 and A2 mating types were detected. Lineages US-22, US-23, and US-24 were generally sensitive to mefenoxam while US-8 was resistant. US-8 and US-24 were primarily pathogenic on potato while US-22 and US-23 were pathogenic on both potato and tomato. Indirect germination was favored at lower temperatures (5 and 10°C) whereas direct germination, though uncommon, was favored at higher temperatures (20 and 25°C). Sporangia of US-24 released zoospores more rapidly than did sporangia of US-22 and US-23. The association of characteristic phenotypic traits with genotype enables the prediction of phenotypic traits from rapid genotypic analyses for improved disease management.

Extremity compartment syndrome and fasciotomy: a literature review.

Trauma surgeons frequently encounter injured limbs at risk for compartment syndrome. This article reviews data regarding the pathophysiology of compartment syndrome, factors in measuring compartment pressures, thresholds for performing fasciotomies, and outcomes from the development of compartment syndromes and performing fasciotomies.

Actions of adiponectin on the excitability of subfornical organ neurons are altered by food deprivation.

Adiponectin (ADP) is a peptide produced by adipose tissue, which acts as an insulin sensitizing hormone. Recent studies have shown that adiponectin receptors (AdipoR1 and AdipoR2) are present in the CNS, and although adiponectin does appear in both circulation and the cerebrospinal fluid there is still some debate as to whether or not ADP crosses the blood brain barrier (BBB). Circumventricular organs (CVO) are CNS sites which lack normal BBB, and thus represent sites at which circulating adiponectin may act to directly influence the CNS. The subfornical organ (SFO) is a CVO that has been implicated in the regulation of energy balance as a consequence of the ability of SFO neurons to respond to a number of different circulating satiety signals including amylin, CCK, PYY and ghrelin. Our recent microarray analysis suggested the presence of adiponectin receptors in the SFO. We report here that the SFO shows a high density of mRNA for both adiponectin receptors (AdipoR1 and AdipoR2), and that ADP influences the excitability of dissociated SFO neurons. Separate subpopulations of SFO neurons were either depolarized (8.9+/-0.9 mV, 21 of 97 cells), or hyperpolarized (-8.0+/-0.5 mV, 34 of 97 cells), by bath application of 10nM ADP, effects which were concentration dependent and reversible. Our microarray analysis also suggested that 48 h of food deprivation resulted in specific increases in AdipoR2 mRNA expression (no effect on AdipoR1 mRNA), observations which we confirm here using real-time PCR techniques. The effects of food deprivation also resulted in a change in the responsiveness of SFO neurons to adiponectin with 77% (8/11) of cells tested responding to adiponectin with depolarization, while no hyperpolarizations were observed. These observations support the concept that the SFO may be a key player in sensing circulating ADP and transmitting such information to critical CNS sites involved in the regulation of energy balance.

Activation of extracellular signal-regulated kinases in social behavior circuits during resident-intruder aggression tests.

Using a variety of experimental methods, a network of brain areas regulating aggressive behaviors has been identified in several groups of vertebrates. However, aggressive behavior expressed in different contexts is associated with different patterns of activity across hypothalamic and limbic brain regions. Previous studies in rodents demonstrated that short day photoperiods reliably increase both male and female aggression versus long day photoperiods. Here we used immunohistochemistry and western blots to examine the effect of photoperiod on phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK) in male California mice (Peromyscus californicus) during resident-intruder tests. Phosphorylated ERK (pERK) can alter neuronal activity in the short term and in the long term acts as a transcription factor. In the posterior bed nucleus of the stria terminalis (BNST) males tested in aggression tests had more pERK positive cells when housed in short days but not long days. This result was replicated in western blot analyses from microdissected BNST samples. In the medial amygdala (MEA), immunostaining and western analyses showed that pERK expression also was generally increased in short days. Immunostaining was also used to examine phosphorylation of cyclic AMP response element binding protein (CREB). CREB can be phosphorylated by pERK as well as other kinases and functions primarily as a transcription factor. Intriguingly, aggressive interactions reduced the number of cells stained positive for phosphorylated CREB in the infralimbic cortex, ventral lateral septum and MEA. This effect was observed in mice housed in long days but not short days. Overall, these data suggest that different (but overlapping) networks of aggressive behavior operate under different environmental conditions.

Population Structure and Resistance to Mefenoxam of Phytophthora capsici in New York State.

In 2006, 2007, and 2008, we sampled 257 isolates of Phytophthora capsici from vegetables at 22 sites in four regions of New York, to determine variation in mefenoxam resistance and population genetic structure. Isolates were assayed for mefenoxam resistance and genotyped for mating type and five microsatellite loci. We found mefenoxam-resistant isolates at a high frequency in the Capital District and Long Island, but none were found in western New York or central New York. Both A1 and A2 mating types were found at 12 of the 22 sites, and we detected 126 distinct multilocus genotypes, only nine of which were found at more than one site. Significant differentiation (FST) was found in more than 98% of the pairwise comparisons between sites; approximately 24 and 16% of the variation in the population was attributed to differences among regions and sites, respectively. These results indicate that P. capsici in New York is highly diverse, but gene flow among regions and fields is restricted. Therefore, each field needs to be considered an independent population, and efforts to prevent movement of inoculum among fields need to be further emphasized to prevent the spread of this pathogen.

The subfornical organ: a central target for circulating feeding signals.

The mechanisms through which circulating ghrelin relays hunger signals to the CNS are not yet fully understood. In this study, we have examined the potential role of the subfornical organ (SFO), a circumventricular structure that lacks the normal blood-brain barrier, as a CNS site in which ghrelin acts to influence the hypothalamic centers controlling food intake. We report that ghrelin increased intracellular calcium concentrations in 28% (12 of 43) of dissociated SFO neurons and that the SFO expresses mRNA for the growth hormone secretagogue receptor. Whole-cell patch recordings from SFO neurons demonstrated that in 29% (9 of 31) of neurons tested ghrelin induced a mean depolarization of 7.4 +/- 0.69 mV, accompanied by an increase in action potential frequency. Voltage-clamp recordings revealed that ghrelin activates a putative nonselective cationic conductance. Previous reports that the satiety signal amylin exerts similar excitatory effects on SFO neurons led us to examine whether these two peptides influence different subpopulations of SFO neurons. Concentration-dependent depolarizing effects of amylin were observed in 59% (28 of 47) of SFO neurons (mean depolarization, 8.32 +/- 0.60 mV). In contrast to ghrelin, voltage-clamp recordings suggest that amylin influences a voltage-dependent current activated at depolarized potentials. We tested single SFO neurons with both peptides and identified cells responsive only to ghrelin (n = 9) and only to amylin (n = 7) but no cells that responded to both peptides. These data support a role for the SFO as a center at which ghrelin and amylin may influence separate subpopulations of neurons to influence the hypothalamic regulation of feeding.