Salamander Neurotransmitters

Cross references:    Salamander Acetylcholine    Salamander Dopamine        
Salamander GABA        Salamander Glutamate        Salamander Serotonin    
Catecholamine      Amphioxus Neurotransmitters       Lamprey Neurotransmitters           

Searching for "salamander neurotransmitters " yielded:   
    PubMed = 742   
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    A review of the neuroembryology of monoamine systems.  
The technique of monoamine histofluorescence has been used successfully for neuroembryologic studies in a number of species ranging from amphibia to the human. Monoamine systems can be visualized early, often before final cell division and migration have taken place. Neuronal cell bodies are seen before axon terminals. Unlike the adult animal, preterminal axons can often be visualized, even in the untreated animal.  
    Anatomical studies have shown major analogies in most of the species studied. CA-containing neuronal cell bodies are restricted to the brainstem and hypothalamus. Those neurons containing 5-HT are largely restricted to the brainstem raphe, although other cell groups may take up 5-HT, or related compounds, under experimental conditions.  
    Monoamine nerve terminals are found throughout the entire nervous system, with some of the regions of highest density being the hypothalamus and striatum.  
    Dynamic studies have indicated that biochemical differentiation precedes morphologic maturity, often by a long period of time. Although attempts have been made to determine a specific role of monoamines in the complex programs of neurogenesis, there is little specific data currently available."  

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    Distribution of substance P-like immunoreactivity in the brain of the newt (Triturus cristatus).  
The distribution of immunoreactive substance P (sP)-containing structures in the newt brain and spinal cord was explored with an indirect immunofluorescence method. Five sP-positive elements were detected:
    perikarya, dots, fibers, pericellular appositions, and pipe-shaped structures.
    Perikarya were seen at the levels of the spinal ganglia, spinal cord, raphe nucleus, interpeduncular nucleus, mesencephalon, preoptic area, infundibulum, dorsocaudal part of the ventral hypothalamus, habenula, and corpus striatum.  
    Pericellular terminals were observed in periventricular areas, known to be rich in catecholaminergic cells; pipe-shaped structures were observed from the corpus striatum to diencephalon, and in mesencephalon.  
    The olfactory nerve and nuclei were devoid of sP-positive elements. Six sP-immunofluorescent pathways were detected. One of them is composed of axons with huge varicosities and extends from the lateral spinal cord area to the mesencephalon. This pathway has not been described as yet in other animals and could be peculiar to the newt."  
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Origins of descending projections to the medulla oblongata and rostral medulla spinalis in the urodele Salamandra salamandra (amphibia).


    The appearance of neural and glial cell markers during early development of the nervous system in the amphibian embryo.  
We conclude that cell-type-specific antibodies can be used to identify neurones and glial cells at early times during neural development and may be useful tools in circumstances where functional identification is difficult."   
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     Striatal afferents in the newt Triturus cristatus.  
In order to investigate the neuronal populations projecting to the corpus striatum in the brain of a urodele, Triturus cristatus, horseradish peroxidase (HRP) retrograde labeling was used in parallel with anterograde degeneration, glyoxylic acid histofluorescence and behavioral testing.  
    Striatal injections of HRP revealed that the main striatal afferent systems originate within the diencephalon, specifically in the dorsal thalamus and paraventricular organ of the hypothalamus. Several small groups of neurons in other diencephalic areas also participate in striatal innervation: proeminentia ventralis, amygdala, contralateral corpus striatum, preoptic area, posterior tuberal nucleus, locus coeruleus and raphe nuclei.  
    Degeneration experiments after mechanical lesion of the paraventricular organ established the existence of a hypothalamostriatal projection. Degenerating axonal profiles were also found in many of the structures already identified as projecting to the striatum, suggesting that the paraventricular organ might influence the striatum not only directly but also indirectly through these other afferent systems.  
    In the paraventricular organ, glyoxylic acid fluorescence histochemistry showed numerous monoamine neurons that corresponded in distribution and morphology to the retrogradely HRP-labeled neurons. Paraventricular-organ-lesioned males displayed a severe impairment of courtship behavior in the form of decreased tail beating and head stepping by the females. This suggests that the regulation of stereotyped hypermotricity might involve the monoamine component of the hypothalamo-striatal projection."  
My comment:   
    I'm very surprised.  I had the impression from Herrick that striatal afferents were mostly olfactory, but this article says: 
Striatal injections of HRP revealed that the main striatal afferent systems originate within the diencephalon, specifically in the dorsal thalamus and paraventricular organ of the hypothalamus. Several small groups of neurons in other diencephalic areas also participate in striatal innervation: proeminentia ventralis, amygdala, contralateral corpus striatum, preoptic area, posterior tuberal nucleus, locus coeruleus and raphe nuclei."  

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My comment
    I need to come back to this. 

    Distribution of catecholaminergic and serotoninergic systems in forebrain and midbrain of the newt, Triturus alpestris (Urodela).  
Mapping of monoaminergic systems in the brain of the newt Triturus alpestris was achieved with antisera against (1) thyrosine hydroxylase (TH), (2) formaldehyde-conjugated dopamine (DA), and (3) formaldehyde-conjugated serotonin (5-HT).  
    In the telencephalon, the striatum was densely innervated by a large number of 5-HT-, DA- and TH-immunoreactive (IR) fibers; IR fibers were more scattered in the amygdala, the medial and lateral forebrain bundles, and the anterior commissure.  
    In the anterior and medial diencephalon, TH-IR perikarya contacting the cerebrospinal fluid (CSF-C perikarya) were located in the preoptic recess organ (PRO), the organum vasculosum laminae terminalis and the suprachiasmatic nucleus. Numerous TH-IR perikarya, not contacting the CSF, were present in the posterior preoptic nucleus and the ventral thalamus. At this level, DA-IR CSF-C neurons were only located in the PRO.  
    In the posterior diencephalon, large populations of 5-HT-IR and DA-IR CSF-C perikarya were found in the paraventricular organ (PVO) and the nucleus infundibularis dorsalis (NID); the dorsal part of the NID additionally presented TH-IR CSF-C perikarya. Most regions of the diencephalon showed an intense monoaminergic innervation.  
    In addition, numerous TH-IR, DA-IR and 5-HT-IR fibers, originating from the anterior and posterior hypothalamic nuclei, extended ventrally and reached the median eminence and the pars intermedia of the pituitary gland.  
    In the midbrain, TH-IR perikarya were located dorsally in the pretectal area. Ventrally, a large group of TH-IR cell bodies and some weakly stained DA-IR and 5-HT-IR neurons were observed in the posterior tuberculum. No dopaminergic system equivalent to the substantia nigra was revealed.  
    The possible significance of the differences in the distribution of TH-IR and DA-IR neurons is discussed, with special reference to the CSF-C neurons."  
My comment
In the telencephalon, the striatum was densely innervated by a large number of 5-HT-, DA- and TH-immunoreactive (IR) fibers ..."  I'm very interested in the striatum since the term is frequently used to include the   Nucleus Accumbens Septi 

149 Related citations:   
My comment:   
    I'll be coming back to this.       

    Monoamines and their metabolites in the amphibian (Ambystoma tigrinum) brain: quantitative changes during metamorphosis and captivity.  
1. Monoamine neurotransmitters (epinephrine, norepinephrine, dopamine, serotonin and some of their metabolites (DOPEG, MHPG, DOPAC, 5-HIAA) were measured by HPLC in extracts from telencephalon (TEL) and diencephalon-midbrain (DM) before, during at the end of metamorphosis.  
    2. During metamorphosis MHPG increased and 5-HIAA decreased in TEL and DM while DOPEG decreased only in DM.  
    3. Monoamine levels were greater in the TEL and a larger increase in MHPG occurred there.  
    4. Captivity without metamorphosis also caused a significant depression of 5-HIAA in TEL and depression of DOPEG, MHPG and DOPAC in DM."  

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    Noradrenergic and adrenergic systems in the brain of the urodele amphibian, Pleurodeles waltlii, as revealed by immunohistochemical methods.  
The distribution of noradrenaline and adrenaline in the brain of the urodele amphibian Pleurodeles waltlii has been studied with antibodies raised against noradrenaline and the enzymes dopamine-beta-hydroxylase and phenylethanolamine-N-methyltransferase.  
    Noradrenaline-containing cell bodies were found in the anterior preoptic area, the hypothalamic nucleus of the periventricular organ, the locus coeruleus and in the solitary tract/area postrema complex at the level of the obex.  
     Noradrenergic fibers are widely distributed throughout the brain innervating particularly the ventrolateral forebrain, the medial amygdala, the lateral part of the posterior tubercle, the parabrachial region and the ventrolateral rhombencephalic tegmentum.  
    Putative adrenergic cell bodies were found immediately rostral to the obex, ventral to the solitary tract.  
    Whereas the cell bodies and their dendrites were Golgi-like stained, axons were more difficult to trace. Nevertheless, some weakly immunoreactive fibers could be traced to the basal forebrain. A comparison of these results with data previously obtained in anurans reveals not only several general features, but also some remarkable species differences."  

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    Development of catecholamine systems in the central nervous system of the newt Pleurodeles waltlii as revealed by tyrosine hydroxylase immunohistochemistry.   
The aim of the present study was to extend our knowledge of the development of catecholamine (CA) systems in the class of amphibians to the order of urodeles.  
    In contrast to previous studies of urodeles, the present study with antisera against tyrosine hydroxylase (TH) and dopamine revealed that CA systems are already present at early embryonic stages of the newt, Pleurodeles waltlii. Although the development from fertilized egg to juvenile in the urodele Pleurodeles lasts twice as long as that in the anuran, Xenopus laevis, and shows less dramatic changes in external morphology, the spatiotemporal sequence of appearance of TH-immunoreactive cell groups is rather similar. 
    An early appearance of TH-immunoreactive cell bodies occurs in the olfactory bulb, the posterior tubercle, the accompanying cell group of the hypothalamic periventricular organ, the suprachiasmatic nucleus, the locus coeruleus, an area immediately ventral to the central canal of the spinal cord, and in the retina. Somewhat later, immunoreactive cells are detected in the posterior thalamic nucleus and in the rostral portion of the midbrain tegmentum, whereas the preoptic cell group is the last one to become TH immunoreactive. 
    The presence of CA systems at early embryonic stages of both anurans and urodeles suggests that these systems are already of functional significance early in development. The maturation of CA neuronal structures in the olfactory and retinal circuitries, which takes place during development earlier in amphibians than in mammals, supports that notion."  

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    Catecholamines and indoleamines in the central nervous system of a urodele amphibian: a microdissection study with emphasis on the distribution of epinephrine. 
Individual brain nuclei and regions of the central nervous system of adult male roughskin newts (Taricha granulosa) were microdissected, and the concentrations of norepinephrine, epinephrine, 3,4-dihydroxyphenylacetic acid, dopamine, 5-hydroxyindoleacetic acid, and serotonin were determined using high performance liquid chromatography (HPLC) with electrochemical detection.  
    The pattern of distribution of these catecholamines and indoleamines revealed many similarities between this urodele and other vertebrates. The highest concentrations of biogenic amines were observed in brainstem, hypothalamic, and basal forebrain structures; the lowest concentrations were observed in the internal granule layer of the olfactory bulb and pallial structures of the telencephalon. High concentrations of catecholamines and indoleamines were found in hypothalamic periventricular regions that are known to include cerebrospinal fluidcontacting, monoamine-containing neuronal cell bodies. The rostral diencephalon, which included the preoptic recess organ, had high concentrations of the primary catecholamines, norepinephrine and dopamine, and extremely high concentrations of the secondary catecholamine epinephrine. The dorsomedial infundibular hypothalamic region, which included the paraventricular organ, had high concentrations of dopamine and serotonin. The lateral infundibular hypothalamic region, which included the nucleus infundibularis dorsalis, had high concentrations of each of the biogenic amines.  
    The results revealed unique patterns of distribution for each of the catecholamines and indoleamines studied, and provided evidence that regions of the hypothalamus that include cerebrospinal fluid-contacting, monoamine-containing neuronal cell bodies are focal regions for the metabolism of multiple biogenic amines."  

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    Characterization of pars intermedia connections in amphibians by biocytin tract tracing and immunofluorescence aided by confocal microscopy.  
Biocytin, recently introduced in neuroanatomical studies, was used as a retrograde tract tracer in combination with immunofluorescence in order to analyse the neurochemical characters of some central neuronal projections to the pars intermedia in two amphibian species, the anuran Rana esculenta and the urodele Triturus carnifex.  
    After biocytin insertions in the pars intermedia, neurons became retrogradely labelled in the suprachiasmatic hypothalamus and the locus coeruleus of the brainstem in both species. Some scattered biocytin-labelled neurons were observed in the preoptic area. Moreover, working on the same sections, immunofluorescence revealed a number of codistributions and, in some cases, colocalization in the same neurons of biocytin labellings and immunopositivity for  
    (1) tyrosine hydroxylase in the suprachiasmatic hypothalamus and the locus coeruleus of Rana and Triturus,  
    (2) gamma-aminobutyric acid in the suprachiasmatic hypothalamus of Rana and Triturus and  
    (3) neuropeptide Y in the suprachiasmatic hypothalamus of Rana.
    The specificity of such colocalizations was fully confirmed using dual-channel confocal laser scanning microscopy analysis."  

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    Immunolocalization of aromatic L-amino acid decarboxylase, tyrosine hydroxylase, dopamine, and serotonin in the forebrain of Ambystoma mexicanum.  
To improve basic knowledge about the neurochemical organization of the urodele brain, and to study discrepancies in the localization of monoaminergic markers, we immunohistochemically charted the distribution of four such markers (tyrosine hydroxylase, aromatic L-amino acid decarboxylase, dopamine, and serotonin) in the axolotl (Ambystoma mexicanum) forebrain. Catecholaminergic and serotoninergic systems were found in similar locations to those seen in other Urodela.  
    As seen in other vertebrates, the localization of the different monoaminergic markers reveals some inconsistencies. Cells that are exclusively tyrosine hydroxylase-immunoreactive are observed in the olfactory bulb, anterior olfactory nucleus/nucleus accumbens region, the epichiasmatic portion of the preoptic nucleus, and in the pars intercalaris thalami, whereas cells that are only labelled by aromatic L-amino acid decarboxylase are seen in the anterior olfactory nucleus/nucleus accumbens region, the bed nuclei of the anterior commissure, the posterior portion of the preoptic nucleus, the ventral hypothalamus, and the pars intercalaris thalami. The presence of cells solely serotonin (5-HT)-immunoreactive is suggested for the nucleus infundibularis dorsalis. Conversely, there were no areas that appeared to be exclusively immunoreactive for dopamine. Double-labelling for aromatic L-amino acid decarboxylase/tyrosine hydroxylase and aromatic L-amino acid decarboxylase/serotonin, together with cell counting, confirmed the existence of neurons that express only one monoaminergic marker in amphibian, supporting the hypothesis that these cells are universally present in the central nervous system of vertebrates."  

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    Descending supraspinal pathways in amphibians. II. Distribution and origin of the catecholaminergic innervation of the spinal cord.   
Immunohistochemical studies with antibodies against tyrosine hydroxylase, dopamine, and noradrenaline have revealed that the spinal cord of anuran, urodele, and gymnophionan (apodan) amphibians is abundantly innervated by catecholaminergic (CA) fibers and terminals. Because intraspinal cells occur in all three orders of amphibians CA, it is unclear to what extent the CA innervation of the spinal cord is of supraspinal origin. In a previous study, we showed that many cell groups throughout the forebrain and brainstem project to the spinal cord of two anurans (the green frog, Rana perezi, and the clawed toad, Xenopus laevis), a urodele (the Iberian ribbed newt, Pleurodeles waltl), and a gymnophionan (the Mexican caecilian, Dermophis mexicanus).  
    To determine the exact site of origin of the supraspinal CA innervation of the amphibian spinal cord, retrograde tracing techniques were combined with immunohistochemistry for tyrosine hydroxylase in the same sections. The double-labeling experiments demonstrated that four brain centers provide CA innervation to the amphibian spinal cord:
    1.) the ventrolateral component of the posterior tubercle in the mammillary region,  
    2.) the periventricular nucleus of the zona incerta in the ventral thalamus,  
    3.) the locus coeruleus, and  
    4.) the nucleus of the solitary tract.
This pattern holds for all three orders of amphibians, except for the CA projection from the nucleus of the solitary tract in gymnophionans. There are differences in the strength of the projections (based on the number of double-labeled cells), but in general, spinal functions in amphibians are controlled by CA innervation from brain centers that can easily be compared with their counterparts in amniotes.  
    The organization of the CA input to the spinal cord of amphibians is largely similar to that described for mammals. Nevertheless, by using a segmental approach of the CNS, a remarkable difference was observed with respect to the diencephalic CA projections."  

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    Distribution and origin of the catecholaminergic innervation in the amphibian mesencephalic tectum.  
The mesencephalic tectum plays a prominent role in integrating both visual and multimodal sensory information essential for normal behavior in amphibians. Activity in the mesencephalic tectum is thought to be modulated by the influence of distinct neurochemical inputs, including the catecholaminergic and the cholinergic systems.  
    In the present study, we have investigated the distribution and the origin of the catecholaminergic innervation of the mesencephalic tectum in two amphibian species, the anuran Rana perezi and the urodele Pleurodeles waltl.  
    Immunohistochemistry for dopamine and two enzymes required for the synthesis of catecholamines, tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH), revealed a complex pattern of catecholaminergic (CA) innervation in the anuran and urodele mesencephalic tectum. Dopaminergic fibers were primarily present in deep tectal layers, whereas noradrenergic (DBH immunoreactive) fibers predominated in superficial layers.  
    Catecholaminergic cell bodies were never observed within the tectum. To determine the origin of this innervation, applications of retrograde tracers into the optic tectum were combined with immunohistochemistry for TH.  
    Results from these experiments demonstrate that dopaminergic neurons in the suprachiasmatic and juxtacommissural nuclei (in Rana) or in the nucleus pretectalis (in Pleurodeles), together with noradrenergic cells of the locus coeruleus, are the sources of CA input to the amphibian mesencephalic tectum. The present results suggest that similar CA modulatory inputs are present in the mesecencephalic tectum of both anurans and urodeles."  

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    Effects of cholinergic and noradrenergic agents on locomotion in the mudpuppy (Necturus maculatus).  
Some neurotransmitters act consistently on the central pattern generator (CPG) for locomotion in a wide range of vertebrates. In contrast, acetylcholine (ACh) and noradrenaline (NA) have various effects on locomotion in different preparations. The roles of ACh and NA have not been studied in amphibian walking, so we examined their effects in an isolated spinal cord preparation of the mudpuppy ( Necturus maculatus).  
    This preparation contains a CPG that produces locomotor activity when N-methyl- D-aspartic acid (NMDA), an excitatory amino acid agonist, is added to the bath.  
    The addition of carbachol, a long acting ACh agonist, to the bath disrupted the walking rhythm induced by NMDA, while not changing the level of activity in flexor and extensor motoneurons.  
    Adding clonidine, an alpha(2)-noradrenergic agonist, had no effect on the NMDA-induced walking rhythm. Physostigmine, an ACh-esterase inhibitor, disrupted the walking rhythm, presumably by potentiating the effects of endogenously released ACh. Atropine, an ACh antagonist that binds to muscarinic ACh receptors, blocked the effects of carbachol, indicating that the action is mediated, at least in part, by muscarinic receptors. In the absence of carbachol, atropine had no effect.  
    Locomotion was not induced by carbachol, atropine or clonidine in a resting spinal cord preparation. Cholinergic actions do not seem to be essential to the CPG for walking in the mudpuppy, but ACh may convert a rhythmic walking state to a more tonic state with occasional bursts of EMG activity for postural adjustments."  

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    Somatostatin-like immunoreactivity in the brain of the urodele amphibian Pleurodeles waltl. Colocalization with catecholamines and nitric oxide. 
The neuronal structures with somatostatin-like immunoreactivity have been studied in the brain of the urodele amphibian Pleurodeles waltl. Intense immunoreactivity was observed in neurons and fibers distributed throughout the brain.  
    Within the telencephalon, the subpallial regions were densely labeled containing both cells and fibers, primarily in the striatum and amygdala.   
    The majority of the somatostatin immunoreactive neurons were located in the preoptic area and hypothalamus, although less numerous cells were also found in the thalamus. A conspicuous innervation of the median eminence was revealed, which arises from the hypothalamic cell populations.  
    In the brainstem, intense fiber labeling was present in the tectum and tegmentum, whereas cell bodies were located only in the tegmentum of the mesencephalon and in the interpeduncular, raphe and reticular nuclei of the rhombencephalon.  
    Longitudinal fiber tracts throughout the brainstem were observed and they continued into the spinal cord in the laterodorsal funiculus.  
    The localization of somatostatin in catecholaminergic and nitrergic neurons was studied by double labeling techniques with antisera against tyrosine hydroxylase and nitric oxide synthase. Catecholamines and somatostatin only colocalized in a cell population in the ventral preoptic area. In turn, the striatum and amygdala contained neurons with somatostatin and nitric oxide synthase.  
    Our results demonstrated that the somatostatin neuronal system in the brain of Pleurodeles waltl is consistent with that observed in anuran amphibians and shares many characteristics with those of amniotes. Colocalization of somatostatin with catecholamines and nitric oxide is very restricted in the urodele brain, but in places that can be easily compared to those reported for mammals, suggesting that interactions between these neurotransmitter systems are a primitive feature shared by tetrapod vertebrates."  

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    Distribution of GABA, glycine, and glutamate in neurons of the medulla oblongata and their projections to the midbrain tectum in plethodontid salamanders.  
In the medulla oblongata of plethodontid salamanders, GABA-, glycine-, and glutamate-like immunoreactivity (ir) of neurons was studied.  Combined tracing and immunohistochemical experiments were performed to analyze the transmitter content of medullary nuclei with reciprocal connections with the tectum mesencephali.  
    The distribution of transmitters differed significantly between rostral and caudal medulla; dual or triple localization of transmitters was present in somata throughout the rostrocaudal extent of the medulla.  
    Regarding the rostral medulla, the largest number of GABA- and gly-ir neurons was found in the medial zone. Neurons of the nucleus reticularis medius (NRM) retrogradely labeled by tracer application into the tectum revealed predominantly gly-ir, often colocalized with glu-ir. The NRM appears to be homologous to the mammalian gigantocellular reticular nucleus, and its glycinergic projection is most likely part of a negative feedback loop between medulla and tectum.  Neurons of the dorsal and vestibular nucleus projecting to the tectum were glu-ir and often revealed additional GABA- and/or gly-ir in the vestibular nucleus. 
    Regarding the caudal medulla, the highest density of GABA- and gly-ir cells was found in the lateral zone. Differences in the neurochemistry of the rostral versus caudal medulla appear to result from the transmitter content of projection nuclei in the rostral medulla and support the idea that the rostral medulla is involved in tecto-reticular interaction. Our results likewise underline the role of the NRM in visual object selection and orientation as suggested by behavioral studies and recordings from tectal neurons."  

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    Profiling neurotransmitter receptor expression in the Ambystoma mexicanum brain.  
Ability to regenerate limbs and central nervous system (CNS) is unique to few vertebrates, most notably the axolotl (Ambystoma sp.). However, despite the fact the neurotransmitter receptors are involved in axonal regeneration, little is known regarding its expression profile.  
    In this project, RT-PCR and qPCR were performed to gain insight into the neurotransmitter receptors present in Ambystoma. Its functional ability was studied by expressing axolotl receptors in Xenopus laevis oocytes by either injection of mRNA or by direct microtransplantation of brain membranes.  
    Oocytes injected with axolotl mRNA expressed ionotropic receptors activated by GABA, aspartate+glycine and kainate, as well as metabotropic receptors activated by acetylcholine and glutamate. Interestingly, we did not see responses following the application of serotonin.  
    Membranes from the axolotl brain were efficiently microtransplanted into Xenopus oocytes and two types of native GABA receptors that differed in the temporal course of their responses and affinities to GABA were observed. Results of this study are necessary for further characterization of axolotl neurotransmitter receptors and may be useful for guiding experiments aimed at understanding activity-dependant limb and CNS regeneration."