Dual-comb mid-infrared spectroscopy with free-running oscillators and absolute optical calibration from a radio-frequency reference.

By using free-running independent femtosecond OPOs with a repetition-rate difference of 500 Hz we demonstrate methane absorption spectroscopy with spectral coverage simultaneously spanning the methane P, Q and R branches and with a resolution of 0.5 cm-1. Absolute optical frequency calibration with an accuracy of 0.25 cm-1 (0.27 nm) is achieved from simultaneous repetition-rate and carrier-envelope-offset frequency measurements, without the need for any optical reference. The calibration technique allows registration and averaging of consecutively acquired dual-comb spectra, leading to a high quality and low-noise absorbance measurement in good agreement with the HITRAN database.

Association of retinal arteriolar dilatation with lower verbal memory: the Edinburgh Type 2 Diabetes Study.

AIMS/HYPOTHESIS: Retinal vascular calibre changes may reflect early subclinical microvascular disease in diabetes. Because of the considerable homology between retinal and cerebral microcirculation, we examined whether retinal vascular calibre, as a proxy of cerebral microvascular disease, was associated with cognitive function in older people with type 2 diabetes. METHODS: A cross-sectional analysis of 954 people aged 60-75 years with type 2 diabetes from the population-based Edinburgh Type 2 Diabetes Study was performed. Participants underwent standard seven-field binocular digital retinal photography and a battery of seven cognitive function tests. The Mill Hill Vocabulary Scale was used to estimate pre-morbid cognitive ability. Retinal vascular calibre was measured from an image field with the optic disc in the centre using a validated computer-based program. RESULTS: After age and sex adjustment, larger retinal arteriolar and venular calibres were significantly associated with lower scores for the Wechsler Logical Memory test, with standardised regression coefficients -0.119 and -0.084, respectively (p < 0.01), but not with other cognitive tests. There was a significant interaction between sex and retinal vascular calibre for logical memory. In male participants, the association of increased retinal arteriolar calibre with logical memory persisted (p < 0.05) when further adjusted for vocabulary, venular calibre, depression, cardiovascular risk factors and macrovascular disease. In female participants, this association was weaker and not significant. CONCLUSIONS/INTERPRETATION: Retinal arteriolar dilatation was associated with poorer memory, independent of estimated prior cognitive ability in older men with type 2 diabetes. The sex interaction with stronger findings in men requires confirmation. Nevertheless, these data suggest that impaired cerebral arteriolar autoregulation in smooth muscle cells, leading to arteriolar dilatation, may be a possible pathogenic mechanism in verbal declarative memory decrements in people with diabetes.

Persistent measles virus infection of mouse neural cells lacking known human entry receptors.

AIMS: Infection of the mouse central nervous system with wild type (WT) and vaccine strains of measles virus (MV) results in lack of clinical signs and limited antigen detection. It is considered that cell entry receptors for these viruses are not present on murine neural cells and infection is restricted at cell entry. METHODS: To examine this hypothesis, virus antigen and caspase 3 expression (for apoptosis) was compared in primary mixed, neural cell cultures infected in vitro or prepared from mice infected intracerebrally with WT, vaccine or rodent neuroadapted viruses. Viral RNA levels were examined in mouse brain by nested and real-time reverse transcriptase polymerase chain reaction. RESULTS: WT and vaccine strains were demonstrated for the first time to infect murine oligodendrocytes in addition to neurones despite a lack of the known MV cell receptors. Unexpectedly, the percentage of cells positive for viral antigen was higher for WT MV than neuroadapted virus in both in vitro and ex vivo cultures. In the latter the percentage of positive cells increased with time after mouse infection. Viral RNA (total and mRNA) was detected in brain for up to 20 days, while cultures were negative for caspase 3 in WT and vaccine virus infections. CONCLUSIONS: WT and vaccine MV strains can use an endogenous cell entry receptor(s) or alternative virus uptake mechanism in murine neural cells. However, viral replication occurs at a low level and is associated with limited apoptosis. WT MV mouse infection may provide a model for the initial stages of persistent MV human central nervous system infections.

Phenotypic relationships among methane production traits assessed under ad libitum feeding of beef cattle.

Angus cattle from 2 beef cattle projects in which daily methane production (MPR) was measured were used in this study to examine the nature of the relationships among BW, DMI, and methane traits of beef cattle fed ad libitum on a roughage diet or a grain-based feedlot diet. In both projects methane was measured using the GreenFeed Emission Monitoring system, which provides multiple short-term breath measures of methane production. The data used for this study were from 119 Angus heifers over 15 d on a roughage diet and 326 Angus steers over 70 d on a feedlot diet. Mean (±SD) age, BW, and DMI were 372 ± 28 d, 355 ± 37 kg, and 8.1 ± 1.3 kg/d for the heifers and 554 ± 86 d, 577 ± 69 kg, and 13.3 ± 2.0 kg/d for the steers, respectively. The corresponding mean MPR was 212 g/d for heifers and 203 g/d for steers. Additional traits studied included methane yield (MY; MPR/DMI), methane intensity (MPR/BW), and 3 forms of residual methane production (RMP), which is a measure of actual minus predicted MPR. For RMP, RMP, and RMP predicted MPR were obtained by regression of MPR on BW, on DMI, and on both DMI and BW, respectively. The 2 data sets were analyzed separately using the same statistical procedures. For both feed types the relationships between MPR and DMI and between MPR and BW were both positive and linear. The correlation between MPR and DMI was similar to that between MPR and BW, although the correlations were stronger for the roughage diet ( = 0.75 for MPR vs. DMI; = 0.74 for MPR vs. BW) than the grain-based diet ( = 0.62 for MPR vs. DMI; = 0.66 for MPR vs. BW). The correlation between MY and DMI was negative and moderate for the roughage ( = -0.68) and grain-based ( = -0.59) diets, a finding that is different from the nonsignificant correlations reported in studies of cattle on a restricted roughage diet. The 3 RMP traits were strongly correlated ( values from 0.76 to 0.99) with each other for both the roughage and the grain-based diets, which indicates that using RMP to lower MPR could provide a result similar to using RMP in cattle. As feed intake (DMI) is more difficult to measure than BW, this result implies that under ad libitum feeding situations in which DMI cannot be measured, RMP can be used to identify higher- or lower-RMP animals with similar levels of effectiveness as RMP.

Optimizing test procedures for estimating daily methane and carbon dioxide emissions in cattle using short-term breath measures.

Respiration chambers are considered the reference method for quantifying the daily CH production rate (MPR) and CO production rate (CPR) of cattle; however, they are expensive, labor intensive, cannot be used in the production environment, and can be used to assess only a limited number of animals. Alternative methods are now available, including those that provide multiple short-term measures of CH and CO, such as the GreenFeed Emission Monitoring (GEM) system. This study was conducted to provide information for optimizing test procedures for estimating MPR and CPR of cattle from multiple short-term CH and CO records. Data on 495 Angus steers on a 70-d ad libitum feedlot diet with 46,657 CH and CO records and on 121 Angus heifers on a 15-d ad libitum roughage diet with 7,927 CH and CO records were used. Mean (SD) age and BW were 554 d (SD 92) and 506 kg (SD 73), respectively, for the steers and 372 d (SD 28) and 348 kg (SD 37), respectively, for the heifers. The 2 data sets were analyzed separately but using the same procedures to examine the reduction in variance as more records are added and to evaluate the level of precision with 2 vs. 3 min as the minimum GEM visit duration for a valid record. The moving averages procedure as well as the repeated measures procedure were used to calculate variances for both CH and CO, starting with 5 records and progressively increasing to a maximum of 80 records. For both CH and CO and in both data sets, there was a sharp reduction in the variances obtained by both procedures as more records were added. However, there was no substantial reduction in the variance after 30 records had been added. Inclusion of records with a minimum of 2-min GEM visit duration resulted in reduction in precision relative to a minimum of 3 min, as indicated by significantly ( < 0.05) more heterogeneous variances for all cases except CH4 in steers. In addition, more records were required to achieve the same level of precision relative to data with minimum GEM visit durations of 3 min. For example, in the steers, 72% reduction in initial variance was achieved with 30 records for both CH and CO when minimum GEM visit duration was 3 min, relative to 45 records when data with a minimum visit duration of 2 min were included. It is concluded from this study that when using records of multiple short-term breath measures of CH or CO for the computation of an animal's MPR or CPR, a minimum of 30 records, each record obtained from a minimum GEM visit duration of 3 min, are required.

VEGF165b, an endogenous C-terminal splice variant of VEGF, inhibits retinal neovascularization in mice.

PURPOSE: Hypoxia driven ocular angiogenesis occurs in a range of ischemic retinopathies including proliferative diabetic retinopathy and retinopathy of prematurity. These conditions are initiated and sustained by hypoxia dependent vascular endothelial growth factor (VEGF) expression in the eye. There are two families of VEGF isoforms formed by differential splicing, the pro-angiogenic VEGF family, known to contribute to ocular neovascularization, and the anti-angiogenic VEGF family, which are downregulated in diabetic retinopathy in humans. The first member of the VEGF family to be isolated was VEGF165b. To determine whether VEGF165b could inhibit hypoxia driven angiogenesis in the eye, the oxygen induced retinopathy mouse model of ocular neovascularization was used. METHODS: 1 ng of recombinant human VEGF165b peptide was injected intraocularly upon return to normoxia after 5 days exposure to 95% oxygen, and neovascularization assessed. RESULTS: VEGF165b significantly inhibited the percentage area of retinal neovascularization from 23+/-3% to 12+/-3.3%, and significantly increased normal vascular areas from 62+/-4% to 74+/-4%. The percentage area of residual ischemic retina was not affected. CONCLUSIONS: These results show that a single injection of VEGF165b can significantly reduce preretinal neovascularization without inhibition of physiological intraretinal angiogenesis. Controlling the balance of VEGF(xxx) to VEGF(xxx) isoforms may therefore be therapeutically valuable in the treatment of proliferative eye diseases such as diabetic retinopathy and age related macular degeneration. The regulation of splicing between these two families of isoforms may provide a novel therapeutic strategy for proliferative eye disease.

Reduction in Staphylococcus aureus bacteraemia rates in patients receiving haemodialysis following alteration of skin antisepsis procedures.

This study examined all cases of Staphylococcus aureus bacteraemia (SAB) in the haemodialysis cohort at the Royal Darwin Hospital, Australia over a seven-year period. Midway through this period, antisepsis for arteriovenous fistulae (AVF) and central venous catheters (CVC) changed from 0.5% chlorhexidine solution to 2% chlorhexidine solution. Rates of SAB episodes were calculated using registry data. Trends in SAB over time were analysed using an interrupted regression analysis. Following the change to 2% chlorhexidine, average SAB rates decreased by 68%, and it is estimated that 0.111 cases of SAB/patient-year were prevented. CVC-related SAB rates remained low throughout. These results support the use of 2% chlorhexidine in skin antisepsis for patients with AVF.

Genetic and phenotypic variance and covariance components for methane emission and postweaning traits in Angus cattle.

Ruminants contribute 80% of the global livestock greenhouse gas (GHG) emissions mainly through the production of methane, a byproduct of enteric microbial fermentation primarily in the rumen. Hence, reducing enteric methane production is essential in any GHG emissions reduction strategy in livestock. Data on 1,046 young bulls and heifers from 2 performance-recording research herds of Angus cattle were analyzed to provide genetic and phenotypic variance and covariance estimates for methane emissions and production traits and to examine the interrelationships among these traits. The cattle were fed a roughage diet at 1.2 times their estimated maintenance energy requirements and measured for methane production rate (MPR) in open circuit respiration chambers for 48 h. Traits studied included DMI during the methane measurement period, MPR, and methane yield (MY; MPR/DMI), with means of 6.1 kg/d (SD 1.3), 132 g/d (SD 25), and 22.0 g/kg (SD 2.3) DMI, respectively. Four forms of residual methane production (RMP), which is a measure of actual minus predicted MPR, were evaluated. For the first 3 forms, predicted MPR was calculated using published equations. For the fourth (RMP), predicted MPR was obtained by regression of MPR on DMI. Growth and body composition traits evaluated were birth weight (BWT), weaning weight (WWT), yearling weight (YWT), final weight (FWT), and ultrasound measures of eye muscle area, rump fat depth, rib fat depth, and intramuscular fat. Heritability estimates were moderate for MPR (0.27 [SE 0.07]), MY (0.22 [SE 0.06]), and the RMP traits (0.19 [SE 0.06] for each), indicating that genetic improvement to reduce methane emissions is possible. The RMP traits and MY were strongly genetically correlated with each other (0.99 ± 0.01). The genetic correlation of MPR with MY as well as with the RMP traits was moderate (0.32 to 0.63). The genetic correlation between MPR and the growth traits (except BWT) was strong (0.79 to 0.86). These results indicate that selection for lower MPR may have undesired effect on animal productivity. On the other hand, MY and the RMPR were either not genetically correlated or weakly correlated with BWT, YWT, and FWT (-0.06 to 0.23) and body composition traits (-0.18 to 0.18). Therefore, selection for lower MY or RMPR would lead to lower MPR without impacting animal productivity. Where the use of a ratio trait (e.g., MY) is not desirable, selection on any of the forms of RMP would be an alternative.

Genomic heritabilities and genomic estimated breeding values for methane traits in Angus cattle.

Enteric methane emissions from beef cattle are a significant component of total greenhouse gas emissions from agriculture. The variation between beef cattle in methane emissions is partly genetic, whether measured as methane production, methane yield (methane production/DMI), or residual methane production (observed methane production - expected methane production), with heritabilities ranging from 0.19 to 0.29. This suggests methane emissions could be reduced by selection. Given the high cost of measuring methane production from individual beef cattle, genomic selection is the most feasible approach to achieve this reduction in emissions. We derived genomic EBV (GEBV) for methane traits from a reference set of 747 Angus animals phenotyped for methane traits and genotyped for 630,000 SNP. The accuracy of GEBV was tested in a validation set of 273 Angus animals phenotyped for the same traits. Accuracies of GEBV ranged from 0.29 ± 0.06 for methane yield and 0.35 ± 0.06 for residual methane production. Selection on GEBV using the genomic prediction equations derived here could reduce emissions for Angus cattle by roughly 5% over 10 yr.

Endothelium-derived agents in pericyte function/dysfunction.

The major components of blood vessels are the vascular endothelium and its supporting smooth muscle. Significant strides have been made in the understanding of the cellular and molecular biology of these two cell types and in particular their interactions have been the subject of much interest and debate over the past two decades. The vascular endothelium is now known to profoundly influence the synthetic and motor functions of the underlying smooth muscle and participate in the pathogenesis of all the major vascular disorders. Similarly, the vascular smooth muscle has important effects on the overlying endothelium, and any disruption in the cellular physiology of either cell type can result in dysfunction with important effects on blood flow and vascular permeability The majority of this accumulated knowledge relates to the vascular cells of the macrocirculation. Pericytes are the supporting cells of the microvasculature and a body of evidence is now available to show that similar regulatory mechanisms and vessel-wall cross-talk exists between these cells and the microvascular endothelium. Nowhere are these interactions more important than in the retinal microcirculation where autoregulation is vital for the maintenance of smooth and uninterrrupted blood flow. This review focuses on the interactions between retinal microvascular endothelial cells and their associated pericytes and examines the role of the endothelial cell and the pericyte in the pathogenesis of disease.

Receptor-mediated endocytosis and intracellular trafficking of insulin and low-density lipoprotein by retinal vascular endothelial cells.

PURPOSE: The authors investigated the receptor-mediated endocytosis (RME) and intracellular trafficking of insulin and low-density lipoprotein (LDL) in cultured retinal vascular endothelial cells (RVECs). METHODS: Low-density lipoprotein and insulin were conjugated to 10 nm colloidal gold, and these ligands were added to cultured bovine RVECs for 20 minutes at 4 degrees C. The cultures were then warmed to 37 degrees C and fixed after incubation times between 30 seconds and 1 hour. Control cells were incubated with unconjugated gold colloid at times and concentrations similar to those of the ligands. Additional control cells were exposed to several concentrations of anti-insulin receptor antibody or a saturating solution of unconjugated insulin before incubation with gold insulin. RESULTS: Using transmission electron microscopy, insulin gold and LDL gold were both observed at various stages of RME. Insulin-gold particles were first seen to bind to the apical plasma membrane (PM) before clustering in clathrin-coated pits and internalization in coated vesicles. Gold was later visualized in uncoated cytoplasmic vesicles, corresponding to early endosomes and multivesicular bodies (MVBs) or late endosomes. In several instances, localized regions of the limiting membrane of the MVBs appeared coated, a feature of endosomal membranes not previously described. After RME at the apical PM and passage through the endosomal system, the greater part of both insulin- and LDL-gold conjugates was seen to accumulate in large lysosome-like compartments. However, a small but significant proportion of the internalized ligands was transcytosed and released as discrete membrane-associated quanta at the basal cell surface. The uptake of LDL gold was greatly increased in highly vacuolated, late-passage RVECs. In controls, anti-insulin receptor antibody and excess unconjugated insulin caused up to 89% inhibition in gold-insulin binding and internalization. CONCLUSION: These results illustrate the internalization and intracellular trafficking by RVECs of insulin and LDL through highly efficient RME, and they provide evidence for at least two possible fates for the endocytosed ligands. This study outlines a route by which vital macromolecules may cross the inner blood-retinal barrier.

Oxytocin and vasopressin secretion in response to stimuli producing learned taste aversions in rats.

Administration of lithium chloride, copper sulfate, and apomorphine to rats each stimulated the secretion of oxytocin (OT) and, to a much lesser degree, arginine vasopressin. These agents are assumed to cause visceral illness in rats because of their effectiveness in promoting the acquisition of learned taste aversions. CuSO4 had a greater effect on plasma OT levels when administered ip rather than iv, whereas LiCl did not, results suggesting that LiCl probably stimulates OT secretion by central chemoreceptor activation whereas CuSO4 acts predominantly by local peritoneal irritation. A causal role for circulating OT in the acquisition of learned taste aversions was not found. These and other findings suggest that peripheral levels of OT may represent a quantifiable marker of visceral illness in rats and therefore might be useful in the interpretation of behavioral studies in which learned taste aversions are produced, provided that other stimuli of neurohypophyseal secretion are absent.

Enhanced sodium appetite in rats with lesions centered on nucleus medianus.

Recent experiments have demonstrated that rats with lesions of the ventral portion of nucleus medianus (vNM) frequently exhibit a chronic and robust hyperdipsia, which occurs only at night. This study indicates that the same brain damage may produce a nocturnal appetite for sodium that is similarly pronounced and persistent. Of 68 rats with vNM lesions, 33 were observed to drink at least 15 ml of 0.51 M NaCl solution per day, and 11 of them consumed more than 30 ml daily. The basis for this impressive consumption of saline is uncertain; the brain-damaged rats had normal sodium concentrations, renin activities, and aldosterone levels in plasma during basal maintenance conditions, and they conserved sodium in urine when maintained on a sodium-deficient diet. Nevertheless, the present results indicate that vNM and/or local fibers of passage may play an important role in the control of sodium appetite, as it does in the control of thirst.

Ascorbate antagonizes the behavioral effects of amphetamine by a central mechanism.

The behavioral response to amphetamine was monitored in rats that received simultaneous intraventricular infusions of saline or ascorbate. Both groups of animals displayed comparable responses, although ascorbate significantly delayed the onset of amphetamine-induced locomotion and rearing. In rats pretreated with a threshold dose of haloperidol (0.025 mg/kg), virtually all aspects of the amphetamine response were attenuated, and this effect was enhanced by ascorbate. In haloperidol-pretreated rats, ascorbate significantly lowered sniffing and forepaw shuffling throughout the amphetamine response. These results suggest that ascorbate antagonizes dopaminergic transmission by a central mechanism.

Characterisation of WE-14 in porcine ocular tissue.

WE-14 is derived from the cell-specific posttranslational processing of chromogranin A (CgA) in subpopulations of neuroendocrine cells and neurons. Region- and site-specific chromogranin A, pancreastatin and WE-14 antisera were employed to study the generation of WE-14 in porcine ocular tissues. No chromogranin A or pancreastatin immunostaining was detected in ocular tissue. Immunohistochemistry detected WE-14 immunostaining in a network of nerve fibre bundles and nerve fibres throughout the limbus, cornea, iris and ciliary body with sparse nerve fibres detected throughout the choroid and sclera. Retinal analysis detected intense WE-14 immunostaining in large ovoid cells in the ganglion cell layer with weak immunostaining in a population of small cells in the inner nuclear layer; weak immunostaining was detected within the fibre layers in the inner plexiform layer. Quantitatively, the highest WE-14 tissue concentration was recorded in aqueous retinal and corneal extracts with lower concentrations in the sclera, choroid and anterior uveal tissues. Chromatographic profiling resolved a minor chromogranin A-like immunoreactant and a predominant immunoreactant co-eluting with synthetic human WE-14. This is the first study to demonstrate that WE-14 is generated in neuronal fibres primarily innervating the anterior chamber and in select cell populations in the retina.

Blockade of both D1- and D2-dopamine receptors inhibits amphetamine-induced ascorbate release in the neostriatum.

In vivo recordings with electrochemically modified microvoltammetric electrodes revealed that several neuroleptic drugs, including haloperidol, clozapine, and thioridazine, blocked the rise in extracellular ascorbate produced by amphetamine in the neostriatum of urethane-anesthetized rats. This effect was also observed in animals that received a combined injection of Sch-23390 and sulpiride, but not when either of these drugs were administered alone or in combination with the 5-HT2 blocker, ritanserin. These results indicate that a combined blockade of D1- and D2-dopamine receptors blocks amphetamine-induced ascorbate release.

Heterogeneous responses of neostriatal neurons to amphetamine in freely moving rats.

Single-unit activity was recorded from the neostriatum of unrestrained, behaving rats. Neuronal discharges were found to vary with specific motor responses, general changes in motor activity, or the presentation of orienting stimuli. In each case, however, 1.0 mg/kg D-amphetamine produced approximately equal numbers of excitations and inhibitions. A subsequent injection of a higher dose (5.0 mg/kg) either produced a greater change in firing rate in the same direction or reversed the direction of the low-dose response. Amphetamine, therefore, does not produce uniformly excitatory effects in the neostriatum of ambulant animals. In fact, the neuronal response to amphetamine appears to reflect a complex interaction of several factors, including ongoing behavior and drug dose.

Short-term effects of dopamine-depleting brain lesions on spontaneous activity of striatal neurons: relation to local dopamine concentration and behavior.

The spontaneous activity of striatal neurons was measured after dopamine (DA)-depleting brain lesions were produced in rats by the neurotoxin 6-hydroxydopamine. The extent of DA depletion was determined using tissue punches from the same regions of striatum in which cell activity was recorded. Results showed that the spontaneous activity of Type II neurons in either the medial or lateral striatum increased only when local DA depletions exceeded 90%; when local depletions were less than 90%, spontaneous firing rates of Type II neurons were equivalent to control values. This finding was consistent with additional observations that ingestive and motor behaviors of the same animals were not disrupted until striatal DA depletions exceeded 90%. It also was found that spontaneous firing rates of neurons in the lateral but not the medial striatum could be at control levels in animals clearly exhibiting aphagia, adipsia and akinesia.

Behavioural and histopathological analyses of ibuprofen treatment on the effect of aggregated Abeta(1-42) injections in the rat.

It has been suggested that inflammatory processes may play a role in the development of Alzheimer's disease (AD), and that nonsteroidal anti-inflammatory drug treatments may provide protection against the onset of AD. In the current study male Wistar rats were trained in two-lever operant chambers under an alternating lever cyclic-ratio ratio (ALCR) schedule. When responding showed no trends, subjects were divided into groups. One group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of aggregated beta-amyloid (Abeta) suspension, and one group was bilaterally injected into the CA3 area of the hippocampus with 5 microl of sterile saline. Subgroups were treated twice daily with 0.1 ml (40 mg/kg) ibuprofen administered orally. The results indicated that chronic administration of ibuprofen protected against detrimental behavioural effects following aggregated Abeta injections. Withdrawal of ibuprofen treatment from aggregated Abeta-injected subjects produced a decline in behavioural performance to the level of the non-treated aggregated Abeta-injected group. Ibuprofen treatment reduced the numbers of reactive astrocytes following aggregated Abeta injection, and withdrawal of ibuprofen resulted in an increase of reactive astrocytes. These results suggest that induced inflammatory processes may play a role in AD, and that ibuprofen treatment may protect against some of the symptoms seen in AD.

Modulation of neostriatal activity by iontophoresis of ascorbic acid.

Iontophoresis (20-80 nA) of ascorbic acid (AA) accelerated the firing rate of approximately one-third of the neurons tested in the anteromedial neostriatum of anesthetized rats. When administered to neostriatal neurons that were activated by the simultaneous ejection of glutamic acid (GLU), AA excited more than two-thirds of the cells examined, including many that were not excited by AA alone. At ejection currents above 80 nA, AA further increased the activity of some GLU-activated neurons, but suppressed the firing rate of others. Electrochemical quantification of AA ejection during iontophoresis indicated that the concentration of AA at the tip of the recording electrode was within reasonable physiological limits. It is concluded that endogenous AA may modulate neuronal activity in the neostriatum.