Gamma-aminobutiric Acid Research Articles

Effect of blockade of synthesis of nitric oxide by L-NAME on the level of free amino acids and biogenic amines in the brain cortex of rats with subtotal cerebral ischemia

Mechanisms of development of ischemic stroke are complex and have not been fully established. The aim of this study was to estimate the changes in the pool of free amino acids and biogenic animes in the brain cortex of rats with subtotal cerebral ischemia (SCI) and treated with L-NAME. Experiment was made on 18 rats: 12 animals were undergoing bilateral filament occlusion of arteries carotid, 6 of them were treated with L-NAME. The analyses of free amino acids levels in the blood plasma extracts were carried out by reversed phase HPLC.Concentrations of several amino acids were elevated during SCI including aspartate, b-alanine, valine and leucine. In contrast, the levels of glutamate, asparagine, treonine, gamma-aminobutiric acid, tyrosine and 5-hydroxiindolylacetate were decreased. The administration of L-NAME partially prevented the imbalance of the amino acids pool due to SCI by normalizing the levels of aspartate, glutamate, asparagine, methionine, gamma-aminobutiric acid, b-alanine, 5-hydroxiindolylacetate. However, the administration of L-NAME has induced an additional imbalance in the amino acids pool in the brain cortex (decrease in the levels of glutamine, histidine, taurine, tryptophan, phenylalanine, tyrosine (in comparison to SCI) and decrease in the levels of treonine and arginine. The imbalance of the amino acids pool induced by the administration of L-NAME during SCI is more severe than the imbalance caused by SCI.

Ghrelin Recruits Specific Subsets of Dopamine and GABA Neurons of Different Ventral Tegmental Area Sub-nuclei

Ghrelin is a stomach-derived hormone that regulates rewarding behaviors and reinforcement by acting on the ventral tegmental area (VTA). The VTA is a complex midbrain structure mainly comprised of dopamine (DA) and gamma-aminobutiric acid (GABA) neurons that are distributed in several VTA sub-nuclei. Here, we investigated the neuroanatomical distribution and chemical phenotype of ghrelin-responsive neurons within the VTA. In wild-type mice, we found that: (1) ghrelin binding cells are present in most VTA sub-nuclei but not in its main target, the nucleus accumbens (Acb); (2) systemically injected ghrelin increases food intake but does neither affect locomotor activity nor the levels of the marker of neuronal activation c-Fos in the VTA sub-nuclei; (3) centrally injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; (4) intra-VTA-injected ghrelin increases food intake, locomotor activity and c-Fos levels in non-DA neurons of all VTA sub-nuclei; (5) both centrally and intra-VTA-injected ghrelin increase c-Fos levels in DA neurons of the parabrachial pigmented VTA sub-nucleus. In genetically modified mice in which a subset of GABA neurons expresses the red fluorescent protein tdTomato, we found that centrally injected ghrelin increases c-Fos levels in GABA neurons of the interfascicular VTA sub-nucleus. These results suggest that ghrelin can recruit specific subsets of VTA neurons in order to modulate food intake and locomotor activity.

The Effectivenes of Red Rice to Decrease Total Cholesterol in Type 2 DM Patients

Diabetes mellitus (DM) is a group of metabolic diseases with hyperglycemia characteristic that happens because anomaly of insulin secretion or insulin activity. Insulin deficiency in type 2 DM caused dislipidemia. Red rice are contain fiber, essential fatty acid and Gamma Amino Butiric Acid (GABA). This research intended to know the effectiveness of red rice to decrease total cholesterol levels of patient with type 2 DM. Clinical test with quasi experimental and research design non randomized control-group pretest-postest design was used for the research method. Total samples of this research are 36 samples. The treated group was given the red rice during 6 days on breakfast and dinner, while the control group did not have any intervention. The research showed that average cholesterol levels in the beginning and finale of treated group was 235,69 mg/dL and 198,56 mg/dL, while average cholesterol levels in the beginning and finale of control group was 235,72 mg/dL and 256,50 mg/dL. From this research, red rice has effective to decrease total cholesterol levels of patients with type 2 DM.Keywords: Diabetes mellitus, Red Rice, Cholesterol total levels

Mycorrhization alters foliar soluble amino acid composition and influences tolerance to Pb in Calopogonium mucunoides

Soil contamination by lead (Pb) is a problem due to the persistence of this element on soil. High amounts of Pb in soil impair plant establishment, however some plants may increase tolerance to heavy metals when colonized by arbuscular mycorrhizal fungi (AMF). The leguminous plant, Calopogonium mucunoides, is Pb-sensitive that is tolerant to Pb when associated to AMF. We performed a chromatographic analysis of foliar free-amino acid in non-mycorrhizal and mycorrhizal plants to determine its relation with Pb tolerance. Mycorrhization caused drastic increase in aspartate, glutamine, glycine, threonine, alanine, isoleucine and gamma-aminobutiric acid (GABA), while depletion of asparagine, histidine and arginine was observed in AMF-associated plants. When grouped according to common metabolic precursor, it was found that amino acids derived from 3-phosphoglicerate and pyruvate was higher in mycorrhizal plants while amino acids derived from glucose-6-phosphate and 2-oxoglutarate were higher in non-mycorrhizal plants; phosphoenolpyruvate and oxaloacetate pathways were not influenced by mycorrhization. Summarizing, mycorrhization changed soluble amino acids profile in C. mucunoides leaves, especially aspartate, alanine and GABA, which may be involved in tolerance to abiotic stress. Additionally the depletion of asparagine, histidine and arginine may be related to a deviation for metabolic pathways not related to protein biosynthesis but to the synthesis of polyamines, especially in the case of arginine. Therefore, we suggest that mycorrhization influence on soluble free amino acid profile in leaves can be one of the factors involved with the attenuation of Pb toxicity in AMF-associated C. mucunoides plants.

Subunit composition of neurotransmitter receptors in the immature and in the epileptic brain.

Neuronal activity is critical for synaptogenesis and the development of neuronal networks. In the immature brain excitation predominates over inhibition facilitating the development of normal brain circuits, but also rendering it more susceptible to seizures. In this paper, we review the evolution of the subunit composition of neurotransmitter receptors during development, how it promotes excitation in the immature brain, and how this subunit composition of neurotransmission receptors may be also present in the epileptic brain. During normal brain development, excitatory glutamate receptors peak in function and gamma-aminobutiric acid (GABA) receptors are mainly excitatory rather than inhibitory. A growing body of evidence from animal models of epilepsy and status epilepticus has demonstrated that the brain exposed to repeated seizures presents a subunit composition of neurotransmitter receptors that mirrors that of the immature brain and promotes further seizures and epileptogenesis. Studies performed in samples from the epileptic human brain have also found a subunit composition pattern of neurotransmitter receptors similar to the one found in the immature brain. These findings provide a solid rationale for tailoring antiepileptic treatments to the specific subunit composition of neurotransmitter receptors and they provide potential targets for the development of antiepileptogenic treatments.

Alleviating effects of exogenous Gamma-aminobutiric acid on tomato seedling under chilling stress

Low temperature during germination and early seedling growth is one of the most significant limiting factors in the productivity of plants. Tomato seedling germination is sensitive to chilling stress. Gamma-aminobutyric acid (GABA), as a non-protein amino acid, involved in various stress tolerances in plants. In this study, 5-day old tomato seedlings were exposed to chilling stress (2 ± 0.05°C for 48h) and then the effects of 0, 100, 250, 500 and 750μmolL(-1) concentrations of GABA on electrolyte leakage, proline and malondialdehyde (MDA) content were investigated. The resultS showed that the antioxidant enzyme activity, electrolyte leakage, MDA and proline content were significantly reduced by GABA treatments. However under chilling stress seedlings treated with GABA exhibited significantly higher sugar and proline contents as compared to un-treated seedlings. These results suggest that GABA treatment protects tomato seedlings from chilling stress by enhancing some antioxidant enzymes activity and reducing MDA content which results in maintaining membrane integrity.

Novel functions of GABA signaling in adult neurogenesis

Neurotransmitter gamma-aminobutiric acid (GABA) through ionotropic GABAA and metabotropic GABAB receptors plays key roles in modulating the development, plasticity and function of neuronal networks. GABA is inhibitory in mature neurons but excitatory in immature neurons, neuroblasts and neural stem/progenitor cells (NSCs/NPCs). The switch from excitatory to inhibitory occurs following the development of glutamatergic synaptic input and results from the dynamic changes in the expression of Na+/K+/2Cl- co-transporter NKCC1 driving Cl- influx and neuron-specific K+/Cl- co-transporter KCC2 driving Cl- efflux. The developmental transition of KCC2 expression is regulated by Disrupted-in-Schizophrenia 1 (DISC1) and brain-derived neurotrophic factor (BDNF) signaling. The excitatory GABA signaling during early neurogenesis is important to the activity/experience-induced regulation of NSC quiescence, NPC proliferation, neuroblast migration and newborn neuronal maturation/functional integration. The inhibitory GABA signaling allows for the sparse and static functional networking essential for learning/memory development and maintenance.

Genomics and pharmacogenomics of schizophrenia.

Schizophrenia (SCZ) is among the most disabling of mental disorders. Several neurobiological hypotheses have been postulated as responsible for SCZ pathogenesis: polygenic/multifactorial genomic defects, intrauterine and perinatal environment-genome interactions, neurodevelopmental defects, dopaminergic, cholinergic, serotonergic, gamma-aminobutiric acid (GABAergic), neuropeptidergic and glutamatergic/N-Methyl-D-Aspartate (NMDA) dysfunctions, seasonal infection, neuroimmune dysfunction, and epigenetic dysregulation. SCZ has a heritability estimated at 60-90%. Genetic studies in SCZ have revealed the presence of chromosome anomalies, copy number variants, multiple single-nucleotide polymorphisms of susceptibility distributed across the human genome, aberrant single nucleotide polymorphisms (SNPs) in microRNA genes, mitochondrial DNA mutations, and epigenetic phenomena. Pharmacogenetic studies of psychotropic drug response have focused on determining the relationship between variation in specific candidate genes and the positive and adverse effects of drug treatment. Approximately, 18% of neuroleptics are major substrates of CYP1A2 enzymes, 40% of CYP2D6, and 23% of CYP3A4; 24% of antidepressants are major substrates of CYP1A2 enzymes, 5% of CYP2B6, 38% of CYP2C19, 85% of CYP2D6, and 38% of CYP3A4; 7% of benzodiazepines are major substrates of CYP2C19 enzymes, 20% of CYP2D6, and 95% of CYP3A4. About 10-20% of Western populations are defective in genes of the CYP superfamily. Only 26% of Southern Europeans are pure extensive metabolizers for the trigenic cluster integrated by the CYP2D6+CYP2C19+CYP2C9 genes. The pharmacogenomic response of SCZ patients to conventional psychotropic drugs also depends on genetic variants associated with SCZ-related genes. Consequently, the incorporation of pharmacogenomic procedures both to drugs in development and drugs on the market would help to optimize therapeutics in SCZ and other central nervous system (CNS) disorders.

Effects of maternal cadmium administration on development of monoaminergic, GABAergic and glutamatergic systems

The effects of maternal exposure to 10 mg Cd/l (as cadmium acetate) in drinking water during gestation and lactation on the development of monoaminergic and aminoacidergic systems were studied in discrete brain areas of the pups: striatum, cerebral cortex, dorsal hippocampus and basal-medial hypothalamus. Hippocampal levels of serotonin and 5-hydroxyindolacetic acid were significantly reduced in rats exposed to Cd whereas the dopamine content was not significantly affected by Cd. Glutamate concentration decreased in hypothalamus and increased in hippocampus, while gamma-aminobutiric acid content decreased only in cerebral cortex. The present results demonstrate that maternal exposure to 10 mg/l of Cd leads to neurochemical disturbances on serotoninergic and aminoacidergic systems during development.

Dysfunctions of Cortical Excitability in Drug-Naïve Posttraumatic Stress Disorder Patients

The investigation of a wide set of transcranial magnetic stimulation (TMS)-related variables in both hemispheres might help to identify a pattern of cortical excitability changes in posttraumatic stress disorder (PTSD) patients, reflecting gamma-amino-butiric acid (GABA)/glutamate balance and dysfunction, and to determine whether some of these variables are related to clinical features. In 20 drug-naive PTSD patients without comorbidity and 16 matched healthy control subjects we tested bilaterally with standard TMS procedures: resting motor threshold (RMT) to single-pulse TMS (reflecting ion channel function), paired-pulse short-latency intracortical inhibition (SICI; mainly reflecting GABA(A) function) and intracortical facilitation (ICF; mainly reflecting glutamatergic function), single-pulse cortical silent period (CSP; mainly reflecting GABA(B)-ergic function), and paired-pulse short-latency afferent inhibition (SAI; reflecting cholinergic mechanisms and their presynaptic GABA(A)-mediated modulation). The PTSD patients showed widespread impairment of GABA(A)-ergic SICI, which was reversed toward facilitation in both hemispheres in one-half of the patients, marked increase of glutamatergic ICF in the right hemisphere, and right-sided impairment of SAI. Illness duration and avoidance symptoms but not anxiety correlated with right-lateralized dysfunctions of cortical excitability. Although the neurobiological complexity of each TMS variable makes current results theoretical, the pattern of cortical excitability accompanying PTSD symptoms suggests a bilateral decrease of the GABA(A)-ergic function. This prevails in the right hemisphere, in association with a relative prevalence of the glutamatergic tone, a new finding that current neuroimaging investigations cannot provide due to the lack of reliable glutamate tracers. Results might help to disclose new pathophysiological aspects of PTSD symptoms, providing a rationale for future neuromodulatory strategies of treatment.

PRECLINICAL STUDY: Baclofen reduces ethanol intake in high‐alcohol‐drinking University of Chile bibulous rats

ABSTRACT Treatment with gamma-aminobutiric acid (GABA(B)) receptor agonist, +/-baclofen, has been shown to reduce ethanol intake in selectively bred Sardinian alcohol-preferring rats. The general goal of the present study was to characterize the high ethanol consumption high-alcohol-drinking University of Chile bibulous (UChB) rats with regard to the anti-alcohol effect of GABA(B) receptor stimulation. UChB rats were treated with the more active enantiomer of baclofen [R(+)-baclofen; at a dose of 1.0, 2.0 or 3.0 mg/kg] administered intraperitoneally once daily for four consecutive days or a single dose. When comparing ethanol and saccharin consumption in a free-choice regimen with unlimited access 24 hours/day, the dose of baclofen required to attenuate ethanol consumption significantly was 1.0 mg/kg administered once a day for three consecutive days while the dose that was sufficient to affect saccharin consumption significantly was 2.0 mg/kg, indicating that baclofen was more potent in reducing ethanol intake by UChB rats than reducing saccharin consumption. The reduction of ethanol or saccharin intake can not be attributed to baclofen-induced motor impairment, since baclofen (1.0, 2.0 or 3.0 mg/kg) did not alter spontaneous locomotor activity in UChB rats. Baclofen dose-dependently suppressed the motor activity stimulated by ethanol administration, a phenomenon mediated by activation of the mesolimbic dopamine system. In conclusion, these results showed that the activation of GABA(B) receptor by R(+)-baclofen reduced ethanol and saccharin consumption, as well as ethanol-induced motor stimulation, implicating the GABA(B) receptor in the neural substrates mediating effects that sustain voluntary ethanol in take in UChB rats.

Receptores y transportadores en la glía de Bergmann: posibles funciones en la fisiología del cerebelo

Bergmann glia is a specialized astrocyte of the vertebrate cerebellar cortex. By its localization and morphology, this glial cell type is tightly related with Purkinje cell, which is the neuron that integrates the different inputs signals in the cerebellum cortex and the unique output of this system.This review makes a description of plasma membrane transporters and receptors in Bergmann glia, which interact with the major neurotransmitters in the central nervous system, glutamate and gamma-aminobutiric acid (GABA). Activity of these proteins is analyzed with respect to their possible role in the regulation of Purkinje cell synaptic activity.

Short-Term Effects of Thyroid Hormones on Cytoskeletal Proteins Are Mediated by GABAergic Mechanisms in Slices of Cerebral Cortex from Young Rats

: Thyroid hormones play important roles in brain function. However, few information is available about the effect of 3,5,3'-triiodo-L-thyronine (T(3)) or thyroxine (T(4)) on the in vitro phosphorylation of intermediate filament (IF) proteins from cerebral cortex of rats. In this study we investigated the involvement of GABAergic mechanisms mediating the effects of T(3) and T(4) on the in vitro incorporation of (32)P into IF proteins from cerebral cortex of 10-day-old male rats. Tissue slices were incubated with or without T(3), T(4), gamma-aminobutiric acid (GABA), kinase inhibitors or specific GABA antagonists and (32)P-orthophosphate for 30 min. The IF-enriched cytoskeletal fraction was extracted in a high salt Triton-containing buffer and the in vitro (32)P incorporation into IF proteins was measured. We first observed that 1 microM T(3) and 0.1 microM T(4) significantly increased the in vitro incorporation of (32)P into the IF proteins studied through the PKA and PKCaMII activities. A similar effect on IF phosphorylation was achieved by incubating cortical slices with GABA. Furthermore, by using specific GABA antagonists, we verified that T(3) induced a stimulatory effect on IF phosphorylation through noncompetitive mechanisms involving GABA(A), beyond GABA(B) receptors. In contrast, T(4) effects were mediated mainly by GABA(B) mechanisms. In conclusion, our results demonstrate a rapid nongenomic action of T(3) and T(4) on the phosphorylating system associated to the IF proteins in slices of cerebral cortex of 10 day-old male rats and point to GABAergic mechanisms mediating such effects.

The molecule-regulators contents after secondary brain injury investigation for prognosis of consequences at remote period

Plasma norepinephrine, epinephrine, dopamine and gamma-aminobutiric acid (GABA) contents in patients blood with secondary brain injury were investigated. Norepinephrine and GABA contents decreasing and epinephrine and dopamine contents increasing were founded. Changes observed in neuromediators contents were founded at the end of hospitalization also. These results pointed to adaptive systems tension and creating of the conditions of a high risk for secondary pathological events development or exacerbation.

Vasomotor centre of medulla - morpho-functional and neurochemical organization

The analysis of ventrolateral medulla morpho-functional and neurochemical organization is the aim of this survey. The date on the system of activation and inhibition of the spinal cord vasomotor neurons is represented. In addition, we discuss the role of catecholamines, substance P, glutamate, gamma-aminobutiric acid as neuromediators in the regulation of circulation.

Postpartum changes in the GABAergic system in the bed nucleus of the accessory olfactory tract

The bed nucleus of the accessory olfactory tract (BAOT) is a sexually dimorphic structure which controls the inhibition/disinhibition of the medial preoptic area in the expression of maternal behavior. Therefore, in the present study we investigated sex differences and the modulation of gamma-aminobutiric-acid (GABA) in the BAOT during the first two postpartum days. Four groups of Wistar rats: control males, control females, 0 h postpartum females and 48 h postpartum females, were used in this experiment. Sex differences in glutamate decarboxylase (GAD) and GABA A α-chain receptor densities were apparent in the BAOT. The hormonal and behavioral postpartum state affects GABAergic activity in the females’ BAOT in two ways: firstly, pregnancy and the first two postpartum days induce an increase in GABA A-receptor and GAD densities; secondly, the intensity of these activities are greater in the left hemisphere than in the right. These changes might be related to the BAOT’s function of inhibiting/disinhibiting maternal behavior.

Pharmacological Induction of Larval Settlement and Metamorphosis in the Blue Mussel Mytilus edulis L.

The blue mussel Mytilus edulis L. is an important aquaculture and fouling species in northern seas. Although the general role of chemical cues for settlement of larvae of the blue mussel has been proposed, few studies have focused on induction of settlement and metamorphosis by pharmacological agents. In this study, the induction of larval settlement of the blue mussel by pharmacological compounds was investigated through a series of laboratory experiments with an aim of identifying artificial cues for laboratory bioassay systems in fouling and antifouling research. Gamma-aminobutiric acid (GABA), dihydroxyphenyl L-alanine (DOPA), isobutyl methylxanthine (IBMX) and acetylcholine chloride (ACH) at 10m 7-10m 2 M as well as KCl at 10-40 mM K+ in excess of the level in normal seawater were tested for their inductive effect on larval settlement. In filtered seawater (FSW) <9% of the larvae settled after 48 h. Elevated K+ and GABA levels had no effect on larval settlement and metamorphosis. DOPA at 10m 5 M and IBMX at 10m 6-10m 4 M induced 41-83% larval settlement and ACH at 10m 7-10m 5 M induced < 40% larval settlement. While the highest settlement rates were observed after 48 h exposure to the chemicals, most of the larvae settled within 24 h. Compounds at concentrations of 10m 3-10m 2 M were either toxic to larvae or retarded the growth of the post-larvae shell. Juveniles resulting from induction by lower concentrations of chemicals had a very high survival rate, completed metamorphosis and grew as well as the juveniles that metamorphosed spontaneously. IBMX at 10m 6-10m 4 M and L-DOPA at 10m 5 M are effective agents for induction of settlement and metamorphosis for future studies using juvenile M. edulis.

Light scattering and in vitro biocompatibility studies of poly (vinyl pyrrolidone) derivatives with amino-acid-dependent groups.

Two poly (vinyl pyrrolidone) (PVP) families with amino-acid residues (glycine, beta-alanine, gamma-aminobutiric acid and epsilon-aminocaproic acid) on the base of the co-polymer N-vinyl pyrrolidone and allyl-glycidyl ether (VP-AGE) and on the base of epoxidized PVP (EPVP) were synthesized. Static and dynamic light scattering measurements of these PVP derivatives in water showed that their structure/ behavior were similar to that of PVP. The bioreactivity was also similar to that of PVP. Further investigation of the immunoreactive properties of the derivatives in in vitro proliferation assays with fresh normal human peripheral blood lymphocytes and monocytes led to the determination of a costimulatory profile for each derivative in terms of polyclonal stimulation, specific antigen presentation, and immunoglobulin secretion. This profile allows the selection of an appropriate derivative as a carrier that would suit the immunoreactivity needs of the immobilized ligand.

In vitro and in vivo effects of formamidines in locust (Locusta migratoria migratorioides)

In vivo and in vitro experiments were used to study the effects of formamidines in the locust, Locusta migratoria migratorioides. In vivo the lethal and the antifeeding effects, in vitro the inhibition of the binding of a selective 3H-ligand to the receptors of octopamine, tyramine, dopamine, serotonin and gamma-amino butiric acid were studied. We have demonstrated that demethylchlordimeform is specific agonist to octopamine receptor, having high affinity to octopamine receptor, a moderate affinitiy to tyramine receptor and a low affinity to dopamine, serotonin and to gamma-amino butiric acid receptors. The demethylated chlordimeform analogoues, demethylchlordimeform and didemethylchlordimeform have higher affinity to the octopamine receptor than the parent compound. The formamidines had a toxic and an antifeeding effects when injected into the locust. The half lethal doses (LD50) and the feeding inhibition were correlated with the affinity of the compounds (Ki). The ring substitutions of the mulecule have alterated the both affinity and in vivo effect of the compounds. The most effective ring substitution pattern is 2,4-disubstitution with a combination of methyl groups or halogens. Our results suggest that the lethal effect of formamidines is mediated through the octopamine receptor.

Electron microscopic data on the neurons of nuclei subpretectalis and posterior-ventralis thalami. A combined immunohistochemical study.

The nucleus rotundus receives GABA-like immunoreactive fibres from the nuclei subpretectalis and postero-ventralis thalami. This result was confirmed by Phaseolus vulgaris leucoagglutinin (PhA-L) anterograde tracer and with electron microscopic (EM) gamma-aminobutiric acid (GABA)-immunogold staining. The detailed electron microscopic analysis of the structure of the neurons in these nuclei revealed that the neurons in the nucleus subpretectalis displayed GABA-like immunoreactivity. In the postero-ventral thalamic nucleus a group of neurons was GABA-positive. The surface of the neurons was covered both with numerous GABA-negative and GABA-like immunoreactive terminals that established asymmetrical and symmetrical synapses, respectively, with the GABA-positive neurons. The GABA-like immunonegative terminals are supposed to be the axon terminals of the collaterals of tecto-rotundal fibres in the subpretectal nucleus and the collateral terminal branches of contralateral tecto-rotundal fibres in the postero-ventralis thalami. In both nuclei, the GABA-like immunoreactive terminals may be developed by the collaterals of local neurons that establish symmetrical synapses. In the Phaseolus lectin-stained preparations these terminals may be labelled. The morphological characteristics of the neurons in the subpretectal and partly, in the posteroventral nuclei are similar to those of interneurons (local circuit neurons) and the numerous asymmetrical and symmetrical axo-somatic synapses, respectively. But these neurons locate outside of their target nucleus, and exert their modulatory effect on rotundo-ectostriatal transmission. Also, a contralateral influence is present in the nucleus rotundus that may interact in the cooperation of the eyes. The neurons of the subpretectal and posteroventral nuclei, similarly to the neurons of isthmic nuclei, are a special group of modulatory neurons with effects at a distance.