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PubMed1995

Intrastriatal and intrasubthalamic stimulation of metabotropic glutamate receptors: a behavioral and Fos immunohistochemical study.

Prior work has shown that intrastriatal injection of the metabotropic glutamate receptor agonist 1S,3R-ACPD results in pronounced contralateral rotation, and the basis for this effect is thought to be increased activity of dopaminergic nigrostriatal neurons. We tested this hypothesis by determining the expression of Fos-like immunoreactivity after intrastriatal injection of 1S,3R-ACPD. Intense Fos-like immunoreactivity was noted in the globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra pars reticulata. Ablation of the subthalamic nucleus 10 days prior to intrastriatal injection of 1S,3R-ACPD abolished rotational behaviour but not Fos-like immunoreactivity in the globus pallidus, entopeduncular nucleus and substantia nigra. Intrasubthalamic injection of 1S,3R-ACPD produced marked contralateral rotation and a pattern of Fos-like immunoreactivity similar to that seen after intrastriatal 1S,3R-ACPD injection. These results suggest that stimulation of striatal metabotropic glutamate receptors inhibits striatal projection neuron activity, while stimulation of subthalamic metabotropic glutamate receptors increases subthalamic nucleus activity. Increased subthalamic nucleus activity is necessary and sufficient for the expression of rotational behavior. These results also suggest that metabotropic glutamate receptor antagonists may be useful in the treatment of Parkinson's disease.

Animals↗

PubMed1989

Distinct afferents to internal and external pallidal segments in the squirrel monkey.

The use of retrograde fluorescence double-labeling method has revealed that the internal (GPi) and external (GPe) segments of globus pallidus in squirrel monkey receive projections from different cell populations in striatum and subthalamic nucleus. Striatal neurons projecting either to GPi or GPe formed wide and nonoverlapping cell bands oriented obliquely and covering large portions of putamen and caudate nucleus. Subthalamic neurons projecting to GPe were more abundant and more laterally located than those projecting to GPi. A few cells branching to GPi and GPe were found in subthalamic nucleus but not in striatum. Thus, different striatal and subthalamic neuronal populations influence GPi and GPe in primates.

Animals↗

PubMed1990

Chronic levodopa treatment alters basal and dopamine agonist-stimulated cerebral glucose utilization.

The effect of chronic levodopa administration on the functional activity of the basal ganglia and its output regions was evaluated by means of the 2-deoxyglucose (2-DG) autoradiographic technique in rats with a unilateral 6-hydroxydopamine lesion of the nigrostriatal pathway. The rates of local cerebral glucose utilization were studied under basal conditions as well as in response to challenge with a selective D1 or D2 dopamine-receptor agonist. Levodopa (100 mg/kg/d, i.p.) was administered for 19 d either continuously via infusion with an osmotic pump or intermittently by twice-daily injections. Following a 3-d washout, glucose utilization was found to be decreased by both levodopa regimens in the nucleus accumbens; intermittent levodopa also decreased glucose utilization in the entopeduncular nucleus, subthalamic nucleus, ventrolateral thalamus, ventromedial thalamus, ventroposterolateral thalamus, and lateral habenula. In control (lesioned and treated chronically with saline) rats, the D1 agonist SKF 38393 (5 mg/kg, i.v.) increased 2-DG uptake in the substantia nigra pars reticulata and entopeduncular nucleus ipsilateral to the lesion by 84% and 56%, respectively. Both continuous and intermittent levodopa blunted the SKF 38393-induced elevation in glucose metabolism in the substantia nigra pars reticulata, while intermittent levodopa also attenuated the increase in the entopeduncular nucleus. The D2 agonist quinpirole (0.4 mg/kg, i.v.) did not increase glucose utilization in any brain region in control animals; following intermittent levodopa treatment, however, quinpirole increased 2-DG uptake by 64% in the subthalamic nucleus and by 39% in the deep layers of the superior colliculus on the ipsilateral side.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1993

D1 dopamine agonist and antagonist effects on regional cerebral glucose utilization in rats with intact dopaminergic innervation.

The effects of stimulation and blockade of the D1 dopamine receptor on regional cerebral glucose utilization (RCGU) were studied using quantitative [14C]2-deoxyglucose autoradiography in naive rats. Systemic administration of the selective D1 antagonist, SCH 23390 (0.5 mg/kg), lowered glucose utilization by 24-28% in the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra pars reticulata (SNr), and motor cortex, suggesting that stimulation of the D1 receptor by endogenous dopamine contributes to basal metabolism in these regions. Administration of SCH 23390 increased RCGU in the lateral habenula, as do selective D2 antagonists. The selective D1 agonist, SKF 38393 (30 mg/kg), increased RCGU in the SNr (up 22%) without affecting the other brain regions which were examined. This modest increase contrasts with the large increase in RCGU (up 100-200%) in the SNr elicited by similar doses of SKF 38393 in rats with acute or chronic dopamine depletion. Systemic administration of amphetamine (5.0 mg/kg), a dopamine releasing agent, increased RCGU in the caudate-putamen (up 33%), globus pallidus (up 23%), subthalamic nucleus (up 46%), entopeduncular nucleus (up 78%), and SNr (up 72%) and lowered RCGU in the lateral habenula (down 43%). All of these amphetamine effects were blocked by pretreatment with either SCH 23390 (0.5 mg/kg) or eticlopride (2.0 mg/kg, a selective D2 antagonist). These results suggest that endogenous dopamine stimulates both D1 and D2 receptors in vivo and provide metabolic evidence to support the concept of a functional linkage of D1 and D2 receptor systems in animals with intact dopaminergic innervation.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed2001

Unilateral lesions of the pedunculopontine nucleus do not alleviate subthalamic nucleus-mediated anticipatory responding in a delayed sensorimotor task in the rat.

Lesions of the subthalamic nucleus (STN) in the rat are known to cause anticipated movements in behavioral tasks requiring a preparatory period before the execution of externally cued conditioned movements. In the present study, we describe the effects of lesions of the pedunculopontine nucleus (PPN), a structure located on the outflow of the STN to lower brainstem and spinal motor nuclei, on the anticipatory responding caused by a unilateral lesion of the STN in a delayed sensorimotor task. Rats were instructed to keep a lever pressed down by the presentation of a composite visual and acoustic signal, and were required to hold the lever pressed until a trigger stimulus occurred after an unpredictable delay. The trigger stimulus required the animals to release the lever and to press a second lever for food reinforcement. The task was evaluated according to analysis of movement parameters and errors made by the animals during the preparative and executive phases of the conditioned movement. An ibotenate lesion was placed into the STN in either side of the brain. This lesion was followed 3 weeks later by an ibotenate lesion of the PPN ipsilaterally to the STN previously lesioned. The results indicate that the anticipatory responding induced by the STN lesion was not alleviated by the subsequent PPN lesion. However, the animals bearing the combined lesion were severely impaired in conditioned responding to salient stimuli involved in the paradigm and showed side-specific lengthening of reaction and movement times without global motor impairments. The results suggest that the anticipatory responses caused by STN lesions do not require the intervention of the PPN and that the disruption of the dopaminergic nigrostriatal pathway following the combined lesion may be responsible for impairments observed.

Animals↗

PubMed1976

Efferent connections of the caudate nucleus in the Virginia opossum.

The efferents of the opossum's caudate nucleus were investigated by charting the the fiber degenerations produced by electrolytic lesions in various parts of this nucleus. By the aid of a modified Fink-Heimer procedure, degenerating fibers were traced from each of the lesions to the small globus pallidus in which they appeared to be distributed in an orderly dorsoventral pattern. Fibers from all lesion sites in the caudate nucleus were found to terminate in the entopedunucular nucleus. In the substantia nigra, caudatofugal-fiber degeneration was confined in all cases to the rostal part of the pars reticulata, and was densest in the medial one-half of this nucleus. Only from lesions in the ventromedial part of the caudate nucleus could degenerating fibers be traced to the nucleus ansae lenticularis. No fiber degeneration could be traced rostrally from the lesions, or to the putamen, red nucleus, subthalamic nucleus, or pons.

Animals↗

PubMed1986

Extensive intraneuronal spread of horseradish peroxidase from a focus of vasogenic edema into remote areas of central nervous system. Observations on mouse central nervous system subjected to cortical cold injury.

A study was made of the uptake of horseradish peroxidase (HRP) into neurons from a cryogenic cortical lesion in the mouse brain associated with vasogenic edema, following intravenous administration of the tracer. Particular emphasis was placed on the axonal spread of HRP from the primary lesion to other areas of the central nervous system. The distribution of HRP was studied by light microscopy, using highly sensitive histochemical methods, 3-144 h after the onset of the injury. Extravasated HRP was taken up into nerve cell bodies in and around the primary lesion, forming different patterns of labelling: (1) granular, (2) diffuse, and (3) a combination of granular and diffuse staining. Granularity is considered to be the result of HRP accumulation in lysosomes occurring in undamaged or slightly damaged nerve cells, whereas the diffuse, non-granular pattern presumably occurs in severely damaged neurons. Nerve cell bodies containing HRP reaction product were also found in the contralateral cortex, ipsilateral thalamus, substantia nigra, amygdala and ventral tegmental area, presumably a consequence of retrograde axonal transport of the tracer from the primary injury. HRP-containing axons were present in the corpus callosum and in the pyramidal tract of the injured hemisphere all the way down to the cervical spinal cord. Labelling of axonal terminals and preterminal axons in the ipsilateral thalamus, entopeduncular nucleus, subthalamic nucleus, substantia nigra and pons indicated anterograde transport of HRP to these regions. Thus very extensive intraneuronal spread of a macromolecular edema component takes place from a primary focal brain lesion to areas located far away from but neuroanatomically connected to this injured region. The brain thus seems to be affected by focal vasogenic edema in many more ways than are recognized at present.

Animals↗

PubMed1990

Metabolic mapping of the effects of intravenous methamphetamine administration in freely moving rats.

The 2-[14C]deoxyglucose method was used to examine the effects of acute intravenous administration of methamphetamine (0.5-2.5 mg/kg) on rates of local cerebral glucose utilization in freely-moving rats. These effects were correlated with the effects of methamphetamine on locomotor activity assessed simultaneously in the same animals. Methamphetamine administration resulted in widespread dose-dependent increases in glucose utilization within structures of the extrapyramidal motor system. Rates of glucose utilization were positively correlated with locomotor activity in the globus pallidus, substantia nigra reticulata, entopeduncular nucleus, subthalamic nucleus, and the lateral cerebellar cortex. In contrast, within the limbic system alterations in metabolic activity were smaller and more selective. Glucose utilization was increased in the nucleus accumbens at all doses tested, but alterations in glucose utilization in the ventral tegmental area, amygdala, and anterior cingulate were observed only at the highest doses of methamphetamine tested. Significant increases in rates of glucose metabolism were also found in the substantia nigra compacta and in the median and dorsal raphe nuclei. Dopamine and serotonin are depleted in these regions, as well as in the ventral tegmental area where glucose utilization was also increased, following chronic treatment with high doses of methamphetamine. These changes in glucose utilization may be indicative of disturbances in the biochemical processes involved in the neurotoxic effects of methamphetamine.

Animals↗

PubMed1999

Lesion-making surgery versus brain stimulation for treatment of Parkinson's disease.

With the resurgence of interest in neurosurgical intervention for the treatment of drug-resistant Parkinson's disease, posteroventral pallidotomy (internal globus pallidus) has become a procedure widely applied by neurosurgeons. In chronic deep brain stimulation, the stimulation target is the same area as the above lesion-making point: the ventralis intermedius thalamic nucleus, subthalamic nucleus, and internal globus pallidus, since deep brain stimulation does not induce brain damage, and it is possible to control the stimulation (frequency and strength). There is also no recurrence. This procedure has the reversibility, selectivity, and adjustability that is ideal for functional neurosurgery. Such chronic stimulation therapy has thus now become an alternative to lesion-making stereotactic surgery. However, stimulation therapy directed at a particular target has more specific effects on particular symptoms of Parkinson's disease, so that an effective stimulation target needs to be selected depending on the nature of the syndrome to be improved. This article presents a review of the most recent reports on how to perform safer and more effective pallidotomy, and of recent basic and clinical reports concerning pallidal stimulation. Some answers to the question of whether or not stimulation therapy is an alternative to lesion-making surgery at the internal globus pallidus to improve parkinsonian syndrome and levodopa-induced dyskinesias are discussed.

Journal Article↗

PubMed1982

GABA-transaminase in the basal ganglia: a pharmacohistochemical study.

A pharmacohistochemical procedure to demonstrate histochemically those cells with the ability to synthesize the GABA-metabolizing enzyme GABA-transaminase has been applied to determine the localization of this enzyme in the basal ganglia. In normal, pharmacologically unmanipulated animals, strong GABA-transaminase activity is present throughout the neuropil in many nuclei of the basal ganglia. The striatum, globus pallidus, entopeduncular nucleus, subthalamic nucleus and substantia nigra are all heavily stained. White matter such as the corpus callosum and internal capsule are unstained. Pretreatment of rats with the irreversible GABA-transaminase inhibitor ethanolamine-O-sulfate resulted in a marked reduction in the general neuropil staining. At a suitable post-injection survival time, cells which had synthesized new GABa-transaminase molecules could be detected. Small, positive neurons were present in the striatum and entopeduncular nucleus, while the globus pallidus, substantia nigra zona reticulata, and the ventral pallidal region contained many large, intensely GABA-transaminase-positive neurons. The results indicate that much of the GABA-transaminase in the basal ganglia is neuronal in origin. The relationship of GABA-transaminase to GABA neurons is discussed.

4-Aminobutyrate Transaminase↗

PubMed1989

Selective distribution of N-acetylaspartylglutamate immunoreactivity in the extrapyramidal system of the rat.

N-Acetylaspartylglutamate (NAAG), a neuron-specific dipeptide, was found by immunocytochemistry to be localized in specific compartments of the extrapyramidal system of the rat. Cellular and neuropil NAAG-like immunoreactivity (NAAG-IR) was evident throughout the pallidum, entopeduncular nucleus, subthalamic nucleus, and all subdivisions of the substantia nigra. By contrast, only a minority of cells of the caudate-putamen and those of the accumbens nucleus stained positively for NAAG. In general, neuronal NAAG-IR was widespread in all ventroposterior output zones of the extrapyramidal system, while cellular immunostaining was greatly reduced in the corticostriate receptive zones. These data suggest that NAAG may serve some neuronal communication function in the extrapyramidal processing circuits and output projections to the thalamus and midbrain. Additionally, neuronal NAAG immunolabeling differentiates corticostriate receptive zones from pallidal and nigral subdivisions of the extrapyramidal system in the rat.

Animals↗

PubMed1986

Effects of the indirect dopaminomimetic diethylpemoline on local cerebral glucose utilization and local cerebral blood flow in the conscious rat.

The changes in local cerebral glucose utilization (LCGU) and local cerebral blood flow (LCBF) following the systemic application of the indirect dopaminomimetic diethylpemoline (50 mg/kg i.v.) were measured in conscious rats using the autoradiographic [14C]2-deoxyglucose and the [14C] iodoantipyrine technique. Increased rates of glucose utilization were observed in the sensorimotor cortex, parafascicular nucleus, ventrolateral nucleus of the thalamus, substantia nigra, caudate nucleus, globus pallidus, red nucleus, subthalamic nucleus, cerebellar cortex and vermis. Cingulate cortex, anteromedial, anteroventral nucleus of the thalamus, habenula and nucleus accumbens showed a decreased LCGU. The determination of LCBF revealed a similar pattern of altered blood flow values. Statistical evaluation of the relationship between glucose utilization and blood flow by regression analysis did not reveal any distinguishable difference between diethylpemoline-treated rats and controls. The data suggest that it is mainly the altered neuronal activity and metabolic demand after dopaminergic stimulation that effect the changes in blood flow rather than a direct dopaminergic effect on brain vasculature.

Animals↗

PubMed1995

Functional correlates of repeated administration of cocaine and apomorphine in the rat.

The [14C]2-deoxyglucose method was applied to measure the effects of repeated (8 consecutive days) administration of apomorphine (0.5 mg/kg/day s.c.) or cocaine (15 mg/kg/day i.p.) on cerebral glucose utilization in freely moving rats. Altered rates of glucose utilization were measured in extrapyramidal motor areas, such as the globus pallidus, entopeduncular nucleus, subthalamic nucleus, substantia nigra and lateral habenula of both cocaine- and apomorphine-treated rats. Furthermore, cocaine-treated animals displayed increased glucose metabolism in the mesolimbic dopaminergic projections, such as nucleus accumbens and olfactory tubercle, and in the hippocampus. These results suggest that altered functional activity within the dopaminergic mesolimbic system may play a role in the process of sensitization to psychomotor stimulant drugs.

Animals↗

PubMed1989

Effects of methylenedioxymethamphetamine on local cerebral glucose utilization in the rat.

The effects of (+-)3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") (5, 10, 15 or 30 mg/kg, i.p.) on local cerebral utilization of glucose were studied by the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake adult male Fischer-344 rats. Statistically significant effects on local utilization of glucose, 5 min after the administration of MDMA were observed in 20 of 60 areas of brain sampled. Marked stimulation was seen in components of the extrapyramidal motor system (substantia nigra, globus pallidus, entopenduncular nucleus, subthalamic nucleus, cerebellar vermis). The limbic system showed decrements in the medial cortex and hippocampal dentate gyrus (outer blade) and the lateral habenula, while there was stimulation in the mammillary body and the basolateral amygdaloid nucleus. Glucose utilization in MDMA-treated rats was reduced in the superior colliculus and medial terminal nucleus of the accessory optic system, but was unchanged in the visual cortex and components of the auditory system. Some of the effects of MDMA on cerebral utilization of glucose resembled those previously reported with l-cocaine, d-amphetamine, and phencyclidine, implicating some common mechanisms in the actions of these drugs.

3,4-Methylenedioxyamphetamine↗

PubMed1989

Brain distribution of idebenone and its effect on local cerebral glucose utilization in rats.

To investigate the possible action sites of a cerebral metabolism activator, idebenone, (6-(10-hydroxydecyl)-2,3-dimethoxy-5-methyl-1,4-benzoquinone), its distribution in the brain and effect on local cerebral glucose utilization (LCGU) were studied in normal (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) with cerebrovascular lesions. 14C-Idebenone distributed rapidly into the brain after intravenous administration (10 mg/kg), and the total 14C contents in the brain at peak time corresponded to 0.45-0.56% of the dosages. An autoradiographic study showed that the 14C levels were higher in the white than in the gray matter. When 14C-idebenone was administered orally (100 mg/kg) and intraperitoneally (30 mg/kg), the total 14C levels were not markedly different among the brain regions of the rats. The concentration of unchanged idebenone was higher in the cerebral cortex, thalamus, and cerebellum than that in the other brain regions. Studies on LCGU demonstrated that idebenone (30 mg/kg/day, i.p., for 3 days) improved the reduction of LCGU in SHRSP with stroke, especially in the temporal cortex, thalamus dorsomedial nucleus, subthalamic nucleus, mamillary body, hippocampus dentate gyrus, caudate-putamen, inferior colliculus, and cerebellar nucleus. Based on these results, possible action sites of idebenone for its main pharmacologic effects are discussed.

Animals↗

PubMed1994

Distribution of the serotonin 5-HT2 receptor family mRNAs: comparison between 5-HT2A and 5-HT2C receptors.

Because of their similarities, serotonin 5-HT2, 5-HT1C, and the recently described 5-HT2F receptors have been classified as members of the 5-HT2 receptor family, and they have been renamed 5-HT2A, 5-HT2C and 5-HT2B, respectively. The regional distribution and cellular localization of mRNA coding for the members of 5-HT2 receptor family were investigated in consecutive tissue sections from the rat brain by in situ hybridization histochemistry. No evidence for the expression of 5-HT2B receptor was found. High levels of 5-HT2A (formerly 5-HT2) receptor mRNA were observed only in few areas, as the frontal cortex, piriform cortex, ventro-caudal part of CA3, medial mammillary nucleus, the pontine nuclei and the motor cranial nerve nuclei in the brainstem, and the ventral horn of the spinal cord. The distribution of 5-HT2A receptor mRNA is generally in good agreement with that of the corresponding binding sites, although discrepancies were sometimes observed. 5-HT2C (formerly 5-HT1C) mRNA was present at very high levels in the choroid plexuses. However, very high levels were also seen in many other brain regions, as the retrosplenial, piriform and entorhinal cortex, anterior olfactory nucleus, lateral septal nucleus, subthalamic nucleus, amygdala, subiculum and ventral part of CA3, lateral habenula, substantia nigra pars compacta, several brainstem nuclei and the whole grey matter of the spinal cord. These results confirm and extend previous observations that 5-HT2C receptor mRNA is present in many brain areas in addition to those autoradiographically shown to have the corresponding binding sites and that 5-HT2C receptor subtype is a principal 5-HT receptor in the brain. From the comparison between their distributions, 5-HT2A and 5-HT2C receptor mRNAs appeared to be expressed in distinct but overlapping sets of brain regions. Both mRNAs coexisted at high levels in the anterior olfactory nucleus, piriform cortex, endopiriform nucleus, claustrum, pyramidal cell layer of the ventral part of CA3, taenia tecta, substantia nigra pars compacta, and several brainstem nuclei. In other regions both mRNAs were present but with different distributions, as the caudate-putamen. These results are also discussed in relation to the physiological meaning of the existence of two so similar receptor subtypes in the brain.

Animals↗

PubMed1987

The organization of nucleus tegmenti pedunculopontinus neurons projecting to basal ganglia and thalamus: a retrograde fluorescent double labeling study in the rat.

The organization of nucleus tegmenti pedunculopontinus (PPN) projections to the basal ganglia and thalamus was studied in the rat by using retrograde transport of fluorescent dyes. Fast blue was injected into the substantia nigra (SN) while Nuclear yellow was delivered to one of the following nuclei: globus pallidus (GP), entopeduncular nucleus, subthalamic nucleus (STN) or parafascicular nucleus of the thalamus. Retrogradely labeled cells were observed throughout the PPN without topographical arrangement. The cells labeled from the SN outnumbered those labeled from other structures. In all cases the majority of cells were single labeled and only a few cells double labeled from SN-GP or SN-STN were found. Labeled cells were either fusiform or multipolar in shape. These data suggest that distinct PPN cells project to their basal ganglia and thalamic targets without a prominent branched organization.

Amidines↗

PubMed1991

Localization and characterization of endothelin receptor binding sites in the rat brain visualized by in vitro autoradiography.

Endothelin binding sites in rat brain were mapped by quantitative in vitro autoradiography employing [125I]endothelin-1 as radioligand. [125I]Endothelin-1 bound with high affinity and specificity to rat cerebellar sections and was potently displaced by unlabelled endothelins (endothelin-1 greater than endothelin-2 = endothelin-3) and sarafotoxin 6B. The highest densities of endothelin binding sites were found in the cerebellum (especially Purkinje cell layer), choroid plexus and median eminence. High densities were found in the supraoptic and paraventricular hypothalamic nuclei, anterior hypothalamic area, ventromedial hypothalamic nucleus, mammillary nuclei and glomerular layer of olfactory bulb. Moderate densities were found in many thalamic nuclei, the pretectal region, interpeduncular nucleus, suprachiasmatic nucleus, raphe nuclei, tegmental nuclei, olfactory ventricle, red nucleus, subthalamic nucleus, central gray, reticular nuclei, vestibular nuclei, oculomotor and trochlear nuclei, hypoglossal nucleus, motor trigeminal nucleus, nucleus of the trapezoid body and lateral cerebellar nucleus. Low but detectable densities of endothelin binding sites were found in medial geniculate nucleus, fields of Ammon's horn, caudate-putamen, globus pallidus, entopeduncular nucleus, substantia nigra, anterior commissure, internal capsule, anterior pituitary, median preoptic nucleus, septohypothalamic nucleus, superior colliculus and area postrema. These patterns were completely abolished by 1 microM unlabelled endothelin-1, -2 and -3 and sarafotoxin S6B. Brain endothelin binding sites show high affinity for endothelin-1, -2 and -3 and sarafotoxin 6B with highest affinity for endothelin-1. Endothelin binding sites show a non-vascular pattern of distribution in the brain, suggesting that the peptide may have widespread functions as a modulator of neuronal function.

Animals↗