The role of plant functional groups mediating climate impacts on carbon and biodiversity of alpine grasslands.

Plant removal experiments allow assessment of the role of biotic interactions among species or functional groups in community assembly and ecosystem functioning. When replicated along climate gradients, they can assess changes in interactions among species or functional groups with climate. Across twelve sites in the Vestland Climate Grid (VCG) spanning 4 °C in growing season temperature and 2000 mm in mean annual precipitation across boreal and alpine regions of Western Norway, we conducted a fully factorial plant functional group removal experiment (graminoids, forbs, bryophytes). Over six years, we recorded biomass removed, soil microclimate, plant community composition and structure, seedling recruitment, ecosystem carbon fluxes, and reflectance in 384 experimental and control plots. The dataset consists of 5,412 biomass records, 360 species-level biomass records, 1,084,970 soil temperature records, 4,771 soil moisture records, 17,181 plant records covering 206 taxa, 16,656 seedling records, 3,696 ecosystem carbon flux measurements, and 1,244 reflectance measurements. The data can be combined with longer-term climate data and plant population, community, ecosystem, and functional trait data collected within the VCG.

Promoting Intergenerational Justice Through Participatory Practices: Climate Workshops as an Arena for Young People's Political Participation.

In the fall of 2019, Trøndelag County Council, Norway, organized a Climate Workshop for children and youth. The intention of the workshop was to include children's and youth's perspectives as a foundation for a policy document titled "How we do it in Trøndelag. Strategy for transformations to mitigate climate change". The workshop involved a range of creative and discussion tools for input on sustainable development and climate politics. In this article, we aim to (1) describe and discuss innovative practices that include children and youth in policymaking related to climate action, and (2) discuss the theoretical implications of such policymaking in relation to children's rights, young citizenship, and intergenerational justice. We employ a generational framework and perceive climate politics as inherently ingrained in intergenerational justice, where no generation has a superior claim to the earth's resources, yet power is unfairly concentrated and accumulated among adult generations. We draw on contributions by various stakeholders involved: Two young workshop participants, two county council policymakers, and an interdisciplinary team of researchers from Childhood Studies and Design.

BrdU Positive Cells Induced in a Genetic Mouse Model of Glaucoma.

Previous studies have shown that eye drop application of the selective α7 nicotinic acetylcholine receptor agonist, PNU-282987, induces neurogenesis of RGCs in adult wild-type rodents. This study was designed to test the hypothesis that PNU-282987 reverses the loss of RGCs associated with glaucoma. A DBA/2J mouse model that auto-induces a glaucoma-like condition in adulthood was used for these studies. Short-term effects using PNU-282987 and BrdU eye drop treatments were examined, as well as the effects of early treatment and the effects in a chronic early treatment group in DBA/2J mice aged 3, 6 and 10 months. With and without treatment, retinas were removed, fixed, immunostained and RGC counts were assessed. IOP measurements were obtained weekly using a Tonolab tonometer. Results showed an average typical loss of BrdU positive RGCs by 29% by 10 months of age in this DBA/2J colony corresponding with a significant increase in IOP. However, the two-week short term application of PNU-282987 and BrdU induced a significant 21% increase in RGCs for DBA/2J mice at all ages. Chronic early PNU-282987 treatment produced a similarly significant increase in RGCs, while acute early treatment had no effect on RGC numbers. IOP measurements were not affected with PNU-282987 treatment. These studies demonstrated that 2-week treatment with PNU-282987, as well as chronic long-term treatment, induced a significant increase in the number of RGCs in the DBA/2J retina, counteracting the effects of the DBA/2J genetic glaucoma-like condition. These results suggest a potential future treatment of degenerative retinal diseases with PNU-282987.

Brain scans from 21,297 individuals reveal the genetic architecture of hippocampal subfield volumes.

The hippocampus is a heterogeneous structure, comprising histologically distinguishable subfields. These subfields are differentially involved in memory consolidation, spatial navigation and pattern separation, complex functions often impaired in individuals with brain disorders characterized by reduced hippocampal volume, including Alzheimer's disease (AD) and schizophrenia. Given the structural and functional heterogeneity of the hippocampal formation, we sought to characterize the subfields' genetic architecture. T1-weighted brain scans (n = 21,297, 16 cohorts) were processed with the hippocampal subfields algorithm in FreeSurfer v6.0. We ran a genome-wide association analysis on each subfield, co-varying for whole hippocampal volume. We further calculated the single-nucleotide polymorphism (SNP)-based heritability of 12 subfields, as well as their genetic correlation with each other, with other structural brain features and with AD and schizophrenia. All outcome measures were corrected for age, sex and intracranial volume. We found 15 unique genome-wide significant loci across six subfields, of which eight had not been previously linked to the hippocampus. Top SNPs were mapped to genes associated with neuronal differentiation, locomotor behaviour, schizophrenia and AD. The volumes of all the subfields were estimated to be heritable (h2 from 0.14 to 0.27, all p < 1 × 10-16) and clustered together based on their genetic correlations compared with other structural brain features. There was also evidence of genetic overlap of subicular subfield volumes with schizophrenia. We conclude that hippocampal subfields have partly distinct genetic determinants associated with specific biological processes and traits. Taking into account this specificity may increase our understanding of hippocampal neurobiology and associated pathologies.

Renal sympathetic nerve activity after catheter-based renal denervation.

BACKGROUND: Catheter-based renal sympathetic denervation (RDN) has been considered a potential treatment for therapy resistant hypertension (RHT). However, in a randomized placebo-controlled trial, RDN did not lead to a substantial blood pressure (BP) reduction. We hypothesized that variation in the reported RDN efficacy might be explained by incomplete nerve disruption as assessed by renal 123I-meta-iodobenzylguanidine (123I-mIBG) scintigraphy. METHODS: In 21 RHT patients (median age 60 years), we performed 123I-mIBG scintigraphy before and 6 weeks after RDN. Additionally, we assessed changes in BP (24 h day, night, and average), plasma- and urinary-catecholamines and plasma renin activity (PRA) before and after RDN. Planar scintigraphy was performed at 15 min and 4 h after 123I-mIBG administration. The ratio of the mean renal (specific) counts vs. muscle (non-specific) counts represented 123I-mIBG uptake. Renal 123I-mIBG washout was calculated between 15 min and 4 h. RESULTS: After RDN office-based systolic BP decreased from 172 to 153 mmHg (p = 0.036), while diastolic office BP (p = 0.531), mean 24 h systolic and diastolic BP (p = 0.602, p = 0.369, respectively), PRA (p = 0.409) and plasma catecholamines (p = 0.324) did not significantly change post-RDN. Following RDN, 123I-mIBG renal uptake at 15 min was 3.47 (IQR 2.26-5.53) compared to 3.08 (IQR 2.79-4.95) before RDN (p = 0.289). Renal 123I-mIBG washout did not change post-RDN (p = 0.230). In addition, there was no significant correlation between the number of denervations and the renal 123I-mIBG parameters. CONCLUSIONS: No changes were observed in renal 123I-mIBG uptake or washout at 6 weeks post-RDN. These observations support incomplete renal denervation as a possible explanation for the lack of RDN efficacy.

Epidemiology and management of hypertension in paediatric and young adult kidney transplant recipients in The Netherlands.

INTRODUCTION: Hypertension in kidney transplant recipients (KTRs) is a risk factor for cardiovascular mortality and graft loss. Data on the prevalence of hypertension and uncontrolled hypertension (uHT) in paediatric and young adult KTRs are scarce. Also, it is unknown whether 'transition' (the transfer from paediatric to adult care) influences control of hypertension. We assessed the prevalence of hypertension and uHT among Dutch paediatric and young adult KTRs and analysed the effects of transition. Additionally, we made an inventory of variations in treatment policies in Dutch transplant centres. METHODS: Cross-sectional and longitudinal national data from living KTRs ≤30 years of age (≥1-year post-transplant, eGFR >20 mL/min) were extracted from the 'RICH Q' database, which comprises information about all Dutch KTRs <19 years of age, and the Netherlands Organ Transplant Registry database for adult KTRs (≥18-30 years of age). We used both upper-limit blood pressure (BP) thresholds for treatment according to Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. uHT was defined as a BP above the threshold. A questionnaire on treatment policies was sent to paediatric and adult nephrologists at eight Dutch transplant centres. RESULTS: Hypertension and uHT were more prevalent in young adult KTRs (86.4 and 75.8%) than in paediatric KTRs (62.7 and 38.3%) according to the KDIGO definition. Time after transplantation was comparable between these groups. Longitudinal analysis showed no evidence of effect of transition on systolic BP or prevalence of uHT. Policies vary considerably between and within centres on the definition of hypertension, BP measurement and antihypertensive treatment. CONCLUSION: Average BP in KTRs increases continuously with age between 6 and 30 years. Young adult KTRs have significantly more uHT than paediatric KTRs according to KDIGO guidelines. Transition does not influence the prevalence of uHT.

Effects of Dietary Sodium Restriction in Kidney Transplant Recipients Treated With Renin-Angiotensin-Aldosterone System Blockade: A Randomized Clinical Trial.

BACKGROUND: In patients with chronic kidney disease receiving renin-angiotensin-aldosterone system (RAAS) blockade, dietary sodium restriction is an often-used treatment strategy to reduce blood pressure (BP) and albuminuria. Whether these effects extend to kidney transplant recipients is unknown. We therefore studied the effects of dietary sodium restriction on BP and urinary albumin excretion (UAE) in kidney transplant recipients receiving RAAS blockade. STUDY DESIGN: Two-center randomized crossover trial. SETTING & PARTICIPANTS: Stable outpatient kidney transplant recipients with creatinine clearance > 30mL/min, BP ≥120/80mmHg, receiving stable RAAS blockade therapy. INTERVENTION: 6-week regular-sodium diet (target, 150mmol/24 h) and a 6-week low-sodium diet (target, 50mmol/24 h). OUTCOMES & MEASUREMENTS: Main outcome parameters were systolic and diastolic BP, UAE, and estimated glomerular filtration rate (eGFR) at the end of each diet period. Dietary adherence was assessed by 24-hour urinary sodium excretion. RESULTS: We randomly assigned 23 kidney transplant recipients, of whom 22 (mean age, 58±8 [SD] years; 50% men; mean eGFR, 51±21mL/min/1.73m(2)) completed the study. One patient withdrew from the study because of concerns regarding orthostatic hypotension on the low-sodium diet. Sodium excretion decreased from 164±50mmol/24 h during the regular-sodium diet to 87±55mmol/24 h during the low-sodium diet (mean difference, -77 [95% CI, -110 to -44] mmol/24 h; P<0.001). Sodium restriction significantly reduced systolic BP from 140±14 to 129±12mmHg (mean difference, -11 [95% CI, -14 to -7] mmHg; P<0.001), diastolic BP from 86±8 to 79±8mmHg (mean difference, -7 [95% CI, -10 to -5] mmHg; P<0.001). We found no significant effect on natural log (ln)-transformed UAE (mean difference, -0.03 [95% CI, -0.6 to 0.6] ln(mg/24 h); P=0.9) or eGFR. LIMITATIONS: No hard end points; small study; small proportion of patients willing to test the intervention; adherence to sodium diet was achieved in 86% of patients. CONCLUSIONS: In stable kidney transplant recipients receiving RAAS blockade, dietary sodium restriction effectively reduces BP without affecting eGFR. Dietary sodium restriction is relevant to BP management in kidney transplant recipients receiving RAAS blockade.

Effects of renal sympathetic denervation on cardiac sympathetic activity and function in patients with therapy resistant hypertension.

BACKGROUND: Renal sympathetic denervation (RSD) is currently being investigated in multiple studies of sympathetically driven cardiovascular diseases such as heart failure and arrhythmias. Our aim was to assess systemic and cardiac sympatholytic effects of RSD by the measurement of cardiac sympathetic activity and cardiovascular parameters. METHODS: A total of 21 consecutive patients with refractory hypertension (daytime ambulatory blood pressure (BP)≥150/100 mmHg despite the use of 3 or more antihypertensive drugs), no evidence for secondary hypertension and normal renovascular anatomy were included. RSD was performed with the Medtronic Symplicity renal denervation catheter with an average of 4.2 (range 3-6) ablations per renal artery. To assess cardiac sympathetic activity, 123I-mIBG cardiac scintigraphy was performed before and 6 weeks after. In addition, the effect of RSD on peripheral BP and cardiac hemodynamics were assessed non-invasively. RESULTS: 123I-mIBG uptake before and after RSD was 1.7±0.4% vs. 1.7±0.5% at 15 min. and 1.4±0.4% vs. 1.5±0.5% after 4 h. As a consequence, washout rate was similar before (33.7±11.7%) and after RSD (30.1±12.6%, p=0.27). In line with earlier RSD studies, a significant drop in systolic office BP (-12.2 mmHg, p=0.04) was detected, whereas the decrease in ambulatory BP was not significant. No changes were seen in heart rate, stroke volume or left ventricular contractility, both in supine position and after standing. CONCLUSION: In concert with previous reports, RSD leads to a significant drop in office BP. However, a reduction in sympathetic activity could not be demonstrated on a cardiac level.

Renal 123I-MIBG Scintigraphy Before and After Kidney Autotransplantation.

A 25-year-old man underwent an autotransplantation of his right kidney because of fibromuscular dysplasia-induced renal artery stenosis and subsequent hypertension. Since transplantation results in complete kidney denervation, it enabled assessment of renal sympathetic nerve activity changes using renal I-MIBG scintigraphy. Before and 2 weeks after transplantation I-MIBG, scintigraphy was performed. Uptake of I-MIBG in the left (control) kidney increased after transplantation with 4% at 15 minutes and 5% at 4 hours postinjection images, whereas I-MIBG uptake in the right transplanted kidney decreased with 21% at 15 minutes and with 29% at 4 hours, demonstrating renal I-MIBG changes after denervation.

Renal denervation of the native kidneys for drug-resistant hypertension after kidney transplantation.

There is a strong rationale for renal denervation (RDN) of the native kidneys in kidney transplant recipients with treatment-resistant hypertension. We present a patient with a stable graft function, who underwent RDN for posttransplant therapy-resistant hypertension (24-h ambulatory blood pressure measurement (ABPM) 143/89 mmHg, while compliantly using five different antihypertensive agents). After RDN, BP measurements and orthostatic complaints required withdrawal of two antihypertensive agents and halving a third. At 6 months, ABPM was 134/84 mmHg and allograft function remained unchanged. This case calls for designing well-designed prospective studies on RDN in kidney transplant recipients.

Neuroprotection of rat retinal ganglion cells mediated through alpha7 nicotinic acetylcholine receptors.

Glutamate-induced excitotoxicity is thought to play an important role in several neurodegenerative diseases in the central nervous system (CNS). In this study, neuroprotection against glutamate-induced excitotoxicity was analyzed using acetylcholine (ACh), nicotine and the α7 specific nicotinic acetylcholine receptor (α7 nAChR) agonist, N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-4-chlorobenzamide hydrochloride (PNU-282987), in cultured adult rat retinal neurons. Adult Long Evans rat retinas were dissociated and retinal ganglion cells (RGCs) were isolated from all other retinal tissue using a two-step panning technique. Once isolated, RGCs were cultured under various pharmacological conditions to demonstrate excitotoxicity and neuroprotection against excitotoxicity. After 3 days, RGCs were immunostained with antibodies against the glycoprotein, Thy 1.1, counted and cell survival was assessed relative to control untreated conditions. 500 µM glutamate induced excitotoxicity in large and small RGCs in an adult rat dissociated culture. After 3 days in culture with glutamate, the cell survival of large RGCs decreased by an average of 48.16% while the cell survival of small RGCs decreased by an average of 42.03%. Using specific glutamate receptor agonists and antagonists, we provide evidence that the excitotoxic response was mediated through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainic acid (KA) and N-methyl-d-aspartate (NMDA) glutamate receptors through an apoptotic mechanism. However, the excitotoxic effect of glutamate on all RGCs was eliminated if cells were cultured for an hour with 10 µM ACh, 100 µM nicotine or 100 nM of the α7 nAChR agonist, PNU-282987, before the glutamate insult. Inhibition studies using 10nM methyllycaconitine (MLA) or α-bungarotoxin (α-Bgt) supported the hypothesis that neuroprotection against glutamate-induced excitotoxicity on rat RGCs was mediated through α7 nAChRs. In immunocytochemical studies, double-labeled experiments using antibodies against Thy 1.1 and α7 nAChR subunits demonstrated that both large and small RGCs contained α7 nAChR subunits. The data presented in this study support the hypothesis that ACh and nicotinic acetylcholine receptor (nAChR) agonists provide neuroprotection against glutamate-induced excitotoxicity in adult rat RGCs through activation of α7 nAChR subunits. These studies lay the groundwork required for analyzing the effect of specific α7 nAChR agonists using in vivo models of excitotoxicity. Understanding the type of ACh receptors involved in neuroprotection in the rat retina could ultimately lead to therapeutic treatment for any CNS disease that involves excitotoxicity.

A field test for host fruit odour discrimination and avoidance behaviour for Rhagoletis pomonella flies in the western United States.

Prezygotic isolation due to habitat choice is important to many models of speciation-with-gene-flow. Habitat choice is usually thought to occur through positive preferences of organisms for particular environments. However, avoidance of non-natal environments may also play a role in choice and have repercussions for post-zygotic isolation that preference does not. The recent host shift of Rhagoletis pomonella (Diptera: Tephritidae) from downy hawthorn, Crataegus mollis, to introduced apple, Malus domestica, in the eastern United States is a model for speciation-with-gene-flow. However, the fly is also present in the western United States where it was likely introduced via infested apples ≤ 60 years ago. R. pomonella now attacks two additional hawthorns in the west, the native C. douglasii (black hawthorn) and the introduced C. monogyna (English ornamental hawthorn). Flight tunnel tests have shown that western apple-, C. douglasii- and C. monogyna-origin flies all positively orient to fruit volatile blends of their respective natal hosts in flight tunnel assays. Here, we show that these laboratory differences translate to nature through field-trapping studies of flies in the state of Washington. Moreover, western R. pomonella display both positive orientation to their respective natal fruit volatiles and avoidance behaviour (negative orientation) to non-natal volatiles. Our results are consistent with the existence of behaviourally differentiated host races of R. pomonella in the west. In addition, the rapid evolution of avoidance behaviour appears to be a general phenomenon for R. pomonella during host shifts, as the eastern apple and downy hawthorn host races also are antagonized by non-natal fruit volatiles.

Calcium preconditioning triggers neuroprotection in retinal ganglion cells.

In the mammalian retina, excitotoxicity has been shown to be involved in apoptotic retinal ganglion cell (RGC) death and is associated with certain retinal disease states including glaucoma, diabetic retinopathy and retinal ischemia. Previous studies from this lab [Wehrwein E, Thompson SA, Coulibaly SF, Linn DM, Linn CL (2004) Invest Ophthalmol Vis Sci 45:1531-1543] have demonstrated that acetylcholine (ACh) and nicotine protects against glutamate-induced excitotoxicity in isolated adult pig RGCs through nicotinic acetylcholine receptors (nAChRs). Activation of nAChRs in these RGCs triggers cell survival signaling pathways and inhibits apoptotic enzymes [Asomugha CO, Linn DM, Linn CL (2010) J Neurochem 112:214-226]. However, the link between binding of nAChRs and activation of neuroprotective pathways is unknown. In this study, we examine the hypothesis that calcium permeation through nAChR channels is required for ACh-induced neuroprotection against glutamate-induced excitotoxicity in isolated pig RGCs. RGCs were isolated from other retinal tissue using a two step panning technique and cultured for 3 days under different conditions. In some studies, calcium imaging experiments were performed using the fluorescent calcium indicator, fluo-4, and demonstrated that calcium permeates the nAChR channels located on pig RGCs. In other studies, the extracellular calcium concentration was altered to determine the effect on nicotine-induced neuroprotection. Results support the hypothesis that calcium is required for nicotine-induced neuroprotection in isolated pig RGCs. Lastly, studies were performed to analyze the effects of preconditioning on glutamate-induced excitotoxicity and neuroprotection. In these studies, a preconditioning dose of calcium was introduced to cells using a variety of mechanisms before a large glutamate insult was applied to cells. Results from these studies support the hypothesis that preconditioning cells with a relatively low level of calcium before an excitotoxic insult leads to neuroprotection. In the future, these results could provide important information concerning therapeutic agents developed to combat various diseases involved with glutamate-induced excitotoxicity.

Gene dosage, expression, and ontology analysis identifies driver genes in the carcinogenesis and chemoradioresistance of cervical cancer.

Integrative analysis of gene dosage, expression, and ontology (GO) data was performed to discover driver genes in the carcinogenesis and chemoradioresistance of cervical cancers. Gene dosage and expression profiles of 102 locally advanced cervical cancers were generated by microarray techniques. Fifty-two of these patients were also analyzed with the Illumina expression method to confirm the gene expression results. An independent cohort of 41 patients was used for validation of gene expressions associated with clinical outcome. Statistical analysis identified 29 recurrent gains and losses and 3 losses (on 3p, 13q, 21q) associated with poor outcome after chemoradiotherapy. The intratumor heterogeneity, assessed from the gene dosage profiles, was low for these alterations, showing that they had emerged prior to many other alterations and probably were early events in carcinogenesis. Integration of the alterations with gene expression and GO data identified genes that were regulated by the alterations and revealed five biological processes that were significantly overrepresented among the affected genes: apoptosis, metabolism, macromolecule localization, translation, and transcription. Four genes on 3p (RYBP, GBE1) and 13q (FAM48A, MED4) correlated with outcome at both the gene dosage and expression level and were satisfactorily validated in the independent cohort. These integrated analyses yielded 57 candidate drivers of 24 genetic events, including novel loci responsible for chemoradioresistance. Further mapping of the connections among genetic events, drivers, and biological processes suggested that each individual event stimulates specific processes in carcinogenesis through the coordinated control of multiple genes. The present results may provide novel therapeutic opportunities of both early and advanced stage cervical cancers.

Acetylcholine neuroprotection against glutamate-induced excitotoxicity in adult pig retinal ganglion cells is partially mediated through alpha4 nAChRs.

In the mammalian retina, excess glutamate release has been shown to be involved in retinal ganglion cell (RGC) death associated with various diseases. Recent studies have determined that activation of alpha7 nicotinic acetylcholine receptors (nAChRs) partially protect isolated RGCs from glutamate-induced excitotoxicity. In this study, we further classify the types of nAChRs involved in neuroprotection against glutamate-induced excitotoxicity using isolated adult pig RGCs. Cells were isolated with a modified two-step immunoselective panning technique designed to isolate RGCs from other retinal neurons. Once isolated, nAChR subunits were identified using a combination of pharmacological and immunocytochemical techniques. In cell culture experiments, a variety of alpha4 nAChR specific agonists were found to have a partial neuroprotective against glutamate-induced excitotoxicity. This neuroprotection was abolished in the presence of the alpha4 nAChR antagonist, dihydro-beta-erythroidine (DHbetaE). Immunocytochemical results localized several nAChR subunits on isolated adult pig RGCs; in particular alpha4, alpha7 and beta2 nAChR subunits. Large RGCs exclusively immunostained with antibodies against alpha7 nAChR subunits whereas alpha4 and beta2 subunits exclusively immunostained only small RGCs. Double label experiments provided evidence that alpha4 and beta2 subunits co-localize on small RGCs. Knowledge of the receptor subtypes responsible for neuroprotection may lead to treatments associated with glutamate-induced excitotoxicity.

Unusual pheromone receptor neuron responses in heliothine moth antennae derived from inter-species imaginal disc transplantation.

Single-cell electrophysiological recordings were obtained from olfactory receptor neurons housed in sensilla trichodea along the adult antennae arising from transplantation of the antennal imaginal discs between larval male Helicoverpa zea and Heliothis virescens. The olfactory receptor neurons from the majority of type C sensilla sampled on transplanted antennae displayed response characteristics consistent with those of the species that donated the antennae. However, some of the sensilla type C sampled in either transplant type contained olfactory receptor neurons that responded in a manner typical of the recipient species or other neurons that have not previously been found in the type C sensilla of either species. The single-cell data help to explain behavioral results showing that some transplant males do fly upwind to both species' pheromone blends, an outcome not expected based on known antennal sensory phenotypes. Our results suggest that host tissue can influence antennal olfactory receptor neuron development, and further that because of a common phylogenetic ancestry the donor tissue has the genetic capability to produce a variety of sensillar and receptor types.

Activation of NMDA receptors linked to modulation of voltage-gated ion channels and functional implications.

Catfish (Ictalurus punctatus) cone horizontal cells contain N-methyl-d-aspartate (NMDA) receptors, the function of which has yet to be determined. In the present study, we have examined the effect of NMDA receptor activation on voltage-gated ion channel activity. NMDA receptor activation produced a long-term downregulation of voltage-gated sodium and calcium currents but had no effect on the delayed rectifying potassium current. NMDA's effect was eliminated in the presence of AP-7. To determine whether NMDA receptor activation had functional implications, isolated catfish cone horizontal cells were current clamped to mimic the cell's physiological response. When horizontal cells were depolarized, they elicited a single depolarizing overshoot and maintained a depolarized steady state membrane potential. NMDA reduced the amplitude of the depolarizing overshoot and increased the depolarized steady-state membrane potential. Both effects of NMDA were eliminated in the presence of AP-7. These results support the hypothesis that activation of NMDA receptors in catfish horizontal cells may affect the type of visual information conveyed through the distal retina.