Biomedical subjects

Richard Paylor

Publications and source records attributed to Richard Paylor.

At least 19 recordsLinked to original sources

PubMed2006

Rai1 duplication causes physical and behavioral phenotypes in a mouse model of dup(17)(p11.2p11.2).

Genomic disorders are conditions that result from DNA rearrangements, such as deletions or duplications. The identification of the dosage-sensitive gene(s) within the rearranged genomic interval is important for the elucidation of genes responsible for complex neurobehavioral phenotypes. Smith-Magenis syndrome is associated with a 3.7-Mb deletion in 17p11.2, and its clinical presentation is caused by retinoic acid inducible 1 (RAI1) haploinsufficiency. The reciprocal microduplication syndrome, dup(17)(p11.2p11.2), manifests several neurobehavioral abnormalities, but the responsible dosage-sensitive gene(s) remain undefined. We previously generated a mouse model for dup(17)(p11.2p11.2), Dp(11)17/+, that recapitulated most of the phenotypes observed in human patients. We have now analyzed compound heterozygous mice carrying a duplication [Dp(11)17] in one chromosome 11 along with a null allele of Rai1 in the other chromosome 11 homologue [Dp(11)17/Rai1(-) mice] in order to study the relationship between Rai1 gene copy number and the Dp(11)17/+ phenotypes. Normal disomic Rai1 gene dosage was sufficient to rescue the complex physical and behavioral phenotypes observed in Dp(11)17/+ mice, despite altered trisomic copy number of the other 18 genes present in the rearranged genomic interval. These data provide a model for variation in copy number of single genes that could influence common traits such as obesity and behavior.

Animals↗

PubMed2006

Secretin receptor-deficient mice exhibit impaired synaptic plasticity and social behavior.

Secretin is a peptide hormone released from the duodenum to stimulate the secretion of digestive juice by the pancreas. Secretin also functions as a neuropeptide hormone in the brain, and exogenous administration has been reported to alleviate symptoms in some patients with autism. We have generated secretin receptor-deficient mice to explore the relationship between secretin signaling in the brain and behavioral phenotypes. Secretin receptor-deficient mice are overtly normal and fertile; however, synaptic plasticity in the hippocampus is impaired and there are slightly fewer dendritic spines in the CA1 hippocampal pyramidal cells. Furthermore, secretin receptor-deficient mice show abnormal social and cognitive behaviors. These findings suggest that the secretin receptor system has an important role in the central nervous system relating to social behavior.

Animals↗

PubMed2006

Dynamic translational and proteasomal regulation of fragile X mental retardation protein controls mGluR-dependent long-term depression.

Genetic deletion of fragile X mental retardation protein (FMRP) has been shown to enhance mGluR-dependent long-term depression (LTD). Herein, we demonstrate that mGluR-LTD induces a transient, translation-dependent increase in FMRP that is rapidly degraded by the ubiquitin-proteasome pathway. Moreover, proteasome inhibitors abolished mGluR-LTD, and LTD was absent in mice that overexpress human FMRP. Neither translation nor proteasome inhibitors blocked the augmentation of mGluR-LTD in FMRP-deficient mice. In addition, mGluR-LTD is associated with rapid increases in the protein levels of FMRP target mRNAs in wild-type mice. Interestingly, the basal levels of these proteins were elevated and their synthesis was improperly regulated during mGluR-LTD in FMRP-deficient mice. Our findings indicate that hippocampal mGluR-LTD requires the rapid synthesis and degradation of FMRP and that mGluR-LTD triggers the synthesis of FMRP binding mRNAs. These findings indicate that the translation, ubiquitination, and proteolysis of FMRP functions as a dynamic regulatory system for controlling synaptic plasticity.

Animals↗

PubMed2006

Phenotypic characterization of Bbs4 null mice reveals age-dependent penetrance and variable expressivity.

Bardet-Biedl syndrome (BBS) is a rare oligogenic disorder exhibiting both clinical and genetic heterogeneity. Although the BBS phenotype is variable both between and within families, the syndrome is characterized by the hallmarks of developmental and learning difficulties, post-axial polydactylia, obesity, hypogenitalism, renal abnormalities, retinal dystrophy, and several less frequently observed features. Eleven genes mutated in BBS patients have been identified, and more are expected to exist, since about 20-30% of all families cannot be explained by the known loci. To investigate the etiopathogenesis of BBS, we created a mouse null for one of the murine homologues, Bbs4, to assess the contribution of one gene to the pleiotropic murine Bbs phenotype. Bbs4 null mice, although initially runted compared to their littermates, ultimately become obese in a gender-dependent manner, females earlier and with more severity than males. Blood chemistry tests indicated abnormal lipid profiles, signs of liver dysfunction, and elevated insulin and leptin levels reminiscent of metabolic syndrome. As in patients with BBS, we found age-dependent retinal dystrophy. Behavioral assessment revealed that mutant mice displayed more anxiety-related responses and reduced social dominance. We noted the rare occurrence of birth defects, including neural tube defects and hydrometrocolpos, in the null mice. Evaluations of these null mice have uncovered phenotypic features with age-dependent penetrance and variable expressivity, partially recapitulating the human BBS phenotype.

Aging↗

PubMed2006

Tbx1 haploinsufficiency is linked to behavioral disorders in mice and humans: implications for 22q11 deletion syndrome.

About 35% of patients with 22q11 deletion syndrome (22q11DS), which includes DiGeorge and velocardiofacial syndromes, develops psychiatric disorders, mainly schizophrenia and bipolar disorder. We previously reported that mice carrying a multigene deletion (Df1) that models 22q11DS have reduced prepulse inhibition (PPI), a behavioral abnormality and schizophrenia endophenotype. Impaired PPI is associated with several psychiatric disorders, including those that occur in 22q11DS, and recently, reduced PPI was reported in children with 22q11DS. Here, we have mapped PPI deficits in a panel of mouse mutants that carry deletions that partially overlap with Df1 and have defined a PPI critical region encompassing four genes. We then used single-gene mutants to identify the causative genes. We show that PPI deficits in Df1/+ mice are caused by haploinsufficiency of two genes, Tbx1 and Gnb1l. Mutation of either gene is sufficient to cause reduced PPI. Tbx1 is a transcription factor, the mutation of which is sufficient to cause most of the physical features of 22q11DS, but the gene had not been previously associated with the behavioral/psychiatric phenotype. A likely role for Tbx1 haploinsufficiency in psychiatric disease is further suggested by the identification of a family in which the phenotypic features of 22q11DS, including psychiatric disorders, segregate with an inactivating mutation of TBX1. One family member has Asperger syndrome, an autistic spectrum disorder that is associated with reduced PPI. Thus, Tbx1 and Gnb1l are strong candidates for psychiatric disease in 22q11DS patients and candidate susceptibility genes for psychiatric disease in the wider population.

Adult↗

PubMed2006

Exaggerated behavioral phenotypes in Fmr1/Fxr2 double knockout mice reveal a functional genetic interaction between Fragile X-related proteins.

Individuals affected by Fragile X syndrome (FXS) experience cognitive impairment, hyperactivity, attention deficits, social anxiety and autistic-like behaviors. FXS results from the loss of expression of the Fragile X mental retardation (FMR1) gene, whose protein product FMRP is thought to play an important role in neuronal function and synaptic plasticity. Two paralogs of FMRP, FXR1P and FXR2P, have been identified, forming the Fragile X-related (FXR) family of proteins. Although the functions of FXR1P and FXR2P are not well understood, there are similarities among all three FXR proteins in gene structure, amino acid sequence, expression pattern and cellular functions. Mouse models have been described for loss of Fmrp, Fxr1p and Fxr2p, the mouse homologs of FMRP, FXR1P and FXR2P. In earlier studies, we found that Fmr1 knockout (KO) mice, which do not express Fmrp, and Fxr2 KO mice, which do not express Fxr2p, show similarities in some behavioral responses such as hyperactivity. To better understand the functional relationship between FMRP and FXR2P, we generated Fmr1 KO, Fxr2 KO, Fmr1/Fxr2 double KO and wild-type control mice as littermates on the same genetic background and examined them in several behavioral assays. Results show that Fmr1/Fxr2 double KO mice have exaggerated behavioral phenotypes in open-field activity, prepulse inhibition of acoustic startle response and contextual fear conditioning when compared with Fmr1 KO mice, Fxr2 KO mice or wild-type littermates. Our findings suggest that Fmr1 and Fxr2 genes contribute in a cooperative manner to pathways controlling locomotor activity, sensorimotor gating and cognitive processes.

Acoustic Stimulation↗

PubMed2006

Mouse models of 22q11 deletion syndrome.

22q11 deletion syndrome (22q11DS) is caused by an interstitial chromosomal microdeletion that encompasses about 40 genes. It is the most common of the microdeletion syndromes. The clinical phenotype, which is complex and variable, includes specific congenital defects of the cardiovascular system, craniofacies, and immune system. In early childhood, patients manifest cognitive impairment, behavioral disorders, and delays in motor development and language acquisition. Adult patients have a high risk for developing serious psychiatric disorders, especially schizophrenia, schizoaffective disorder, and bipolar disorder. The great majority of patients have an identical or near identical chromosomal deletion, and genotype-phenotype correlations have not been established. Indeed, little progress was made toward resolving the complex clinical phenotype until the deletion was successfully modeled in the mouse. In recent years, through a variety of mouse mutants that carry multigene and single gene mutations, we have learned that mutation in a single gene, Tbx1, is responsible for most of the congenital defects seen in the mouse models and in patients. We now face a greater challenge as we attempt to use the mouse to address the pathogenesis of the behavioral and psychiatric disorders associated with 22q11DS. Significant progress has already been made, and recent studies in the mouse suggest that several genes from the deleted region affect behavior and might contribute to disease burden in patients.

Animals↗

PubMed2006

Mouse Dach2 mutants do not exhibit gross defects in eye development or brain function.

Drosophila dachshund is a critical regulator of eye, brain, and limb formation. Vertebrate homologs, Dach1 and Dach2, are expressed in the developing retina, brain, and limbs, suggesting functional conservation of the dachshund/Dach gene family. Dach1 mutants die postnatally, but exhibit grossly normal development. Here we report the generation of Dach2 mutant mice. Although deletion of Dach2 exon 1 results in abrogation of RNA expression, Dach2 mutants are viable and fertile. Histochemical analysis reveals grossly normal Dach2 mutant eye development. In addition, a battery of neurological assays failed to yield significant differences in behavior between Dach2 mutants and controls. We discuss these findings in the light of published observations of DACH2 mutations in the human population. Finally, to test the functional conservation hypothesis, we generated Dach2; Dach1 double mutant mice. Dach double mutants die after birth, similar to Dach1 homozygotes. However, unlike Drosophila dachshund mutants that lack eyes and exhibit leg truncations, the eyes and limbs of Dach double mutants are present, suggesting differences between Dach and dachshund gene function during embryonic eye and limb formation.

Animals↗

PubMed2005

The use of behavioral test batteries, II: effect of test interval.

Test batteries are commonly used to assess the behavioral phenotype of genetically modified and inbred strains of mice. However, few systematic studies have been employed to address several key issues concerning the use of a test battery. The current study was designed to address whether inter-test interval affects behavioral performance. Male mice of 3 different inbred strains and one F1 hybrid strain were randomly assigned to either a test battery with 1 week inter-test intervals, or a rapid test battery with 1-2 day inter-test intervals. The test battery included a neurological exam, open-field activity, light-dark exploration, rotarod test, prepulse inhibition, and startle habituation. The experiment was repeated with female animals of 2 different strains. As expected, there were strain differences on each of the behavioral assays; however, there was no major difference in performance between mice of the standard test battery and the rapid test battery. Similar results were found with females. These results indicate that the interval between most tests could be as little as 1-2 days, with little significant effect on overall performance. Thus, it is possible with the current test battery to reduce the inter-test interval to facilitate the rate of studying and identifying behavioral phenotypes in mice.

Analysis of Variance↗

PubMed2005

Deletion of the beta 2 nicotinic acetylcholine receptor subunit alters development of tolerance to nicotine and eliminates receptor upregulation.

RATIONALE: Chronic nicotine exposure induces both tolerance and upregulation of [3H]nicotine binding sites in rodent and human brain. However, the mechanism for chronic tolerance is unclear because a direct relationship between tolerance and receptor upregulation is not consistently observed. OBJECTIVES: In the present experiments, the role of beta2* nicotinic acetylcholine receptors (nAChRs) on tolerance development and nAChR upregulation was examined following chronic nicotine treatment of beta2 wild-type (+/+), heterozygous (+/-), and null mutant (-/-) mice. METHODS: Saline or nicotine (1, 2, or 4 mg/kg/h) was infused intravenously for 10 days. Locomotor activity and body temperature responses were measured before and after nicotine challenge injection to observe changes in nicotine sensitivity. [3H]Epibatidine binding was then measured in ten brain regions. RESULTS: Beta2+/+ mice developed dose-dependent tolerance and upregulation of [3H]epibatidine binding sites. In contrast, beta2-/- mice, initially less sensitive to acute nicotine's effects, became more sensitive following treatment with the lowest chronic dose (1 mg/kg/h). Beta2-/- mice treated with 4.0 mg/kg/h nicotine were no longer supersensitive, indicating that tolerance developed at this higher dose. However, these changes in nicotine sensitivity occurred in the absence of any nAChR changes in either low- or high-affinity [3H]epibatidine sites. Responses of beta2+/- mice were intermediate between wild-type and mutant mice. CONCLUSIONS: Upregulation of nAChRs in vivo requires the presence of the beta2 subunit. Changes in nicotine sensitivity occurred both in the presence (beta2+/+) and absence (beta2-/-) of beta2* nAChRs and suggest that mechanisms involving both beta2* and non-beta2* nAChR subtypes modulate adaptation to chronic nicotine exposure.

Animals↗

PubMed2005

Deletion of the alpha7 nicotinic receptor subunit gene results in increased sensitivity to several behavioral effects produced by alcohol.

BACKGROUND: The finding that most people with alcoholism are also heavy smokers prompted several research groups to evaluate the effects of ethanol on neuronal nicotinic acetylcholine receptor (nAChR) function. Data collected in vitro indicate that physiologically relevant concentrations of ethanol inhibit the functional activation of homomeric alpha7 nAChRs, which are one of the most abundant nAChR subtypes expressed in the mammalian brain. The studies outlined here used alpha7 gene knockout (null mutant) mice to evaluate the potential role of alpha7 nAChRs in modulating selected behavioral and physiological effects produced by ethanol. METHODS: Current evidence indicates that many responses to ethanol are not genetically correlated. Therefore, the authors measured the effects of acute administration of ethanol on several behaviors that are altered by both ethanol and nicotine: two tests of locomotor activity, acoustic startle, prepulse inhibition of acoustic startle, and body temperature. Ethanol-induced durations of loss of righting reflex and ethanol elimination rates were also determined. These studies used null mutant (alpha7(-/-)) and wild-type (alpha7(-/-)) mice. RESULTS: Relative to alpha7(+/+) mice, alpha7(-/-) mice were more sensitive to the activating effects of ethanol on open-field activity, ethanol-induced hypothermia, and duration of loss of the righting response. Deletion of the alpha7 gene did not influence the effects of ethanol on Y-maze crossing or rearing activities, acoustic startle, or prepulse inhibition of startle. Gene deletion did not alter ethanol metabolism. CONCLUSIONS: These results indicate that some but not all of the behavioral effects of ethanol are mediated in part by effects on nAChRs that include the alpha7 subunit and may help to explain the robust association between alcohol consumption and the use of tobacco.

Acoustic Stimulation↗

PubMed2004

Abnormalities of social interactions and home-cage behavior in a mouse model of Rett syndrome.

Rett syndrome (RTT) is an autistic spectrum disorder with a known genetic basis. RTT is caused by loss of function mutations in the X-linked gene MECP2 and is characterized by loss of acquired motor, social and language skills in females beginning at 6-18 months of age. MECP2 mutations also cause non-syndromic mental retardation in males and females, and abnormalities of MeCP2 expression in the brain have been found in autistic spectrum disorders. We studied home-cage behavior and social interactions in a mouse model of RTT (Mecp2(308/Y)) carrying a mutation similar to common RTT causing alleles. Young adult mutant mice showed abnormal home-cage diurnal activity in the absence of motor skill deficits. Nesting, a phenotype related to social behavior, and social interactions were both impaired in these animals. Mecp2(308/Y) mice showed deficits in nest building and decreased nest use. Although there were no differences in aggression or exploration of novel inanimate stimuli, mutant mice took less initiative and were less decisive approaching unfamiliar males and spent less time in close vicinity to them in several social interaction paradigms. The abnormalities of diurnal activity and social behavior in Mecp2(308/Y) mice are reminiscent of the sleep/wake dysfunction and autistic features of RTT. These data suggest that MECP2 regulates the expression and/or function of genes involved in social behavior. The study of Mecp2(308/Y) mice will allow the identification of the molecular basis of social impairment in RTT and related autistic spectrum disorders.

Age Factors↗

PubMed2004

Behavioral characterization of mouse models for Smith-Magenis syndrome and dup(17)(p11.2p11.2).

Contiguous gene syndromes (CGS) refer to a group of disorders associated with chromosomal rearrangements in which the phenotype is thought to result from altered copy number of physically linked dosage-sensitive genes. Smith-Magenis syndrome and [dup(17)(p11.2p11.2)] are CGS associated with a heterozygous deletion or duplication of band p11.2 of chromosome 17, respectively. We previously constructed animal models for these CGSs by engineering rearranged chromosomes carrying a deletion/deficiency [Df(11)17] (Del mutant) or a duplication [Dp(11)17 ] (Dup mutant) of the syntenic region on mouse chromosome 11. Here we present a behavioral analysis of these models indicating that heterozygous male mice carrying the engineered deletion or the duplication are hypoactive or hyperactive, respectively. In addition, male Dup mutant mice, but not Del mutant mice, have impaired contextual fear conditioning. Circadian rhythm studies revealed period length differences in Del mutant mice, but not Dup mutant mice. These results indicate that some of the behavioral abnormalities are gene dosage sensitive, whereas other behavioral abnormalities are specific to mice carrying the deletion or the duplication and can be observed in a sex preferential manner. Our findings suggest that there is a gene(s) present in this defined genomic interval that is responsible for behavioral abnormalities in the mouse, as has been shown for the human syntenic region.

Animals↗

PubMed2004

Null mutant analysis of responses to nicotine: deletion of beta2 nicotinic acetylcholine receptor subunit but not alpha7 subunit reduces sensitivity to nicotine-induced locomotor depression and hypothermia.

The nicotinic acetylcholine receptor (nAChR) subtypes alpha4beta2 and alpha7 comprise the majority of brain nicotine-binding sites. Classical genetic strategies using inbred mice and their hybrids suggest that nicotine's effects on locomotor activity and body temperature are influenced by alpha4beta2 but not alpha7 receptors. To evaluate directly the role of these nicotinic subtypes on responses to nicotine, beta2 and alpha7 null mutant (-/-) mice, as well as wild-type (+/+) and heterozygous (+/-) mice, were tested for baseline body temperature and locomotion and nicotine (0-1.5 mg/kg)-induced changes in these responses. Basal responses for these measures were similar for all beta2 genotypes, but baseline Y-maze activity was higher in alpha7-/- mice compared with alpha7+/+ mice. Following nicotine injection, dose-dependent decreases in body temperature and locomotor activity were observed for all three genotypes of both beta2 and alpha7 mice. Although responses in alpha7 mice did not differ among genotypes, beta2 gene deletion was found to have a gene-dependent effect on nicotine's effects. beta2-/- mice were less sensitive to nicotine-induced locomotor depression and hypothermia at low nicotine doses (.25-.5 mg/kg) but were no different from beta2+/+ mice at the highest doses tested (1.0-1.5 mg/kg). Residual responses at high nicotine doses in beta2-/- mice as well as responses in all alpha7 and beta2 mouse genotypes were mediated by nicotinic receptors, since mecamylamine (1.0 mg/kg) blocked all responses following 1.0 mg/kg nicotine. This finding suggests receptors that include the beta2 nAChR subunit partially mediate nicotine's effects on locomotor activity and body temperature.

Animals↗

PubMed2003

Mice lacking Tropomodulin-2 show enhanced long-term potentiation, hyperactivity, and deficits in learning and memory.

Actin filaments control cell morphology and are essential to the growth of dendritic spines and the plasticity of hippocampal long-term potentiation (LTP). The length of these filaments is regulated in muscle and nonmuscle cell types by tropomodulins 1-4 (Tmod1-4), a family of proteins that cap the pointed ends of actin filaments. To investigate whether tropomodulins could play a role in synaptic plasticity, learning, memory, or behavior, we created mice lacking Tropomodulin-2 (Tmod2), which is highly expressed in neuronal structures. Tmod2(lacZ-/-) mice are viable and fertile and exhibit no gross morphological or anatomical abnormalities, but behavioral analysis found hyperactivity, reduced sensorimotor gating, and impaired learning and memory. Electrophysiological analysis revealed enhanced LTP in Tmod2(lacZ-/-) mice. These studies suggest that Tmod2 plays a role in behavior, learning, memory, and synaptic plasticity.

Animals↗

PubMed2003

The nicotinic acetylcholine receptor subunit alpha 5 mediates short-term effects of nicotine in vivo.

Nicotine, acting at pentameric neuronal nicotinic acetylcholine receptors (nAChRs), is the primary addictive component in tobacco. At low doses, it affects attention, learning, memory, anxiety, cardiovascular responses, thermoregulation, and nociception. At high doses, nicotine produces more drastic behaviors and eventually induces tonic-clonic seizures in rodents. In mammals, several subunits of the nAChRs have been cloned, including eight alpha and three beta subunits. To study the physiological role of the alpha 5 subunit, we have generated alpha 5-deficient mice. These mice have a generally healthy appearance and are normal in a standard battery of behavioral tests. However, the sensitivity of alpha 5 mutant mice to nicotine-induced behaviors and seizures is dramatically reduced compared with their wild-type littermates. These animals have a normal brain anatomy and normal levels of mRNA for other nAChR subunits, namely alpha 4, alpha 6, alpha 7, beta 2, and beta 4. In addition, (125)I-epibatidine and [(125)I]alpha-bungarotoxin binding in the brains of alpha 5-deficient mice is normal. Together, these results suggest a direct involvement of the alpha 5 subunit in the observed phenotypes.

Animals↗

PubMed2002

Behavioral and physiological mouse assays for anxiety: a survey in nine mouse strains.

In order to find better and new treatments for anxiety in humans, a variety of paradigms are used to study anxiety-related processes in rodents. We studied mice in two different anxiety-related assays: the physiological stress-induced hyperthermia (SIH) paradigm and the behavioral light-dark exploration (LD) test. Eight inbred strains (129S6/SvEvTac, 129S1/SvImJ, A/J, BALB/cByJ, C3H/HeJ, C57BL/6J, DBA/2J, and FVB/NJ) and one outbred strain (CD1-ICR) were tested in both assays repeatedly. This study describes the first strain survey for the SIH paradigm. All strains showed an SIH response, but the magnitude of the response varied between lines. The inbred strain distribution pattern for the behavioral responses in the LD assay was not correlated with the SIH response. The lack of a significant correlation suggests that there is no genetic relation between such responses. Mice could be tested repeatedly in both assays without affecting the results. A new paradigm, in which both assays were combined, elucidated that behavioral responses were not altered by segments of the SIH paradigm. In contrast, exposure to the light-dark box instead of the home-cage showed a strain-dependent effect on the physiological response. We conclude that a combination of behavioral and physiological responses might lead to a better understanding in anxiety-related processes.

Animals↗

PubMed2002

Synaptic vesicle depletion correlates with attenuated synaptic responses to prolonged repetitive stimulation in mice lacking alpha-synuclein.

Although the mutation of alpha-synuclein, a protein associated with presynaptic vesicles, is implicated in the etiology and pathogenesis of Parkinson's disease, the biological function of the normal protein is unknown. Mice that lack alpha-synuclein have been generated by homologous recombination in embryonic stem cells. Electron microscopic examination of hippocampal synapses revealed a striking selective deficiency of undocked vesicles without affecting docked vesicles. Field recording of CA1 synapses in hippocampal slices from the mutant mice demonstrated normal basal synaptic transmission, paired-pulse facilitation, and response to a brief train of high-frequency stimulation (100 Hz, 40 pulses) that exhausts only docked vesicles. In contrast, the alpha-synuclein knock-out mice exhibited significant impairments in synaptic response to a prolonged train of repetitive stimulation (12.5 Hz, 300 pulses) capable of depleting docked as well as reserve pool vesicles. Moreover, the replenishment of the docked vesicles by reserve pool vesicles after depletion was slower in the mutant synapses. Thus, alpha-synuclein may be required for the genesis and/or maintenance of a subset of presynaptic vesicles, those in the "reserve" or "resting" pools. These results reveal, for the first time, the normal function of endogenous alpha-synuclein in regulating synaptic vesicle mobilization at nerve terminals.

Amphetamine↗