Dataset Information

Integrin-mediated regulation of synaptic morphology, transmission, and plasticity.

ABSTRACT: Volado, the gene encoding the Drosophila alphaPS3-integrin, is required for normal short-term memory formation (Grotewiel et al., 1998), supporting a role for integrins in synaptic modulation mechanisms. We show that the Volado protein (VOL) is localized to central and peripheral larval Drosophila synapses. VOL is strongly concentrated in a subpopulation of synaptic boutons in the CNS neuropil and to a variable subset of synaptic boutons at neuromuscular junctions (NMJs). Mutant morphological and functional synaptic phenotypes were analyzed at the NMJ. Volado mutant synaptic arbors are structurally enlarged, suggesting VOL negatively regulates developmental synaptic sprouting and growth. Mutant NMJs exhibit abnormally large evoked synaptic currents and reduced Ca(2+) dependence of transmission. Strikingly, multiple forms of Ca(2+)- and activity-dependent synaptic plasticity are reduced or absent. Conditional Volado expression in mutant larvae largely rescues normal transmission and plasticity. Pharmacologicially disrupting integrin function at normal NMJs phenocopies features of mutant transmission and plasticity within 30-60 min, demonstrating that integrins acutely regulate functional transmission. Our results provide direct evidence that Volado regulates functional synaptic plasticity processes and support recent findings implicating integrins in rapid changes in synaptic efficacy and in memory formation.

SUBMITTER: Rohrbough J

PROVIDER: S-EPMC6772806 | biostudies-literature | 2000 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Integrin-mediated regulation of synaptic morphology, transmission, and plasticity.

Rohrbough J J Grotewiel M S MS Davis R L RL Broadie K K

The Journal of neuroscience : the official journal of the Society for Neuroscience 20000901 18

Volado, the gene encoding the Drosophila alphaPS3-integrin, is required for normal short-term memory formation (Grotewiel et al., 1998), supporting a role for integrins in synaptic modulation mechanisms. We show that the Volado protein (VOL) is localized to central and peripheral larval Drosophila synapses. VOL is strongly concentrated in a subpopulation of synaptic boutons in the CNS neuropil and to a variable subset of synaptic boutons at neuromuscular junctions (NMJs). Mutant morphological an ...[more]

PMID: 10995831

Similar Datasets

Project description:The basolateral amygdala (BLA) integrates sensory input from cortical and subcortical regions, a function that requires marked synaptic plasticity. Here we provide evidence that cytochrome P450 aromatase (AROM), the enzyme converting testosterone to 17?-estradiol (E2), contributes to the regulation of this plasticity in a sex-specific manner. We show that AROM is expressed in the BLA, particularly in the basolateral nucleus (BL), in male and female rodents. Systemic administration of the AROM inhibitor letrozole reduced spine synapse density in the BL of adult female mice but not in the BL of male mice. Similarly, in organotypic corticoamygdalar slice cultures from immature rats, treatment with letrozole significantly reduced spine synapses in the BL only in cultures derived from females. In addition, letrozole sex-specifically altered synaptic properties in the BL: in acute slices from juvenile (prepubertal) female rats, wash-in of letrozole virtually abolished long-term potentiation (LTP), whereas it did not prevent the generation of LTP in the slices from males. Together, these data indicate that neuron-derived E2 modulates synaptic plasticity in rodent BLA sex-dependently. As protein expression levels of AROM, estrogen and androgen receptors did not differ between males and females and were not sex-specifically altered by letrozole, the findings suggest sex-specific mechanisms of E2 signaling.SIGNIFICANCE STATEMENT The basolateral amygdala (BLA) is a key structure of the fear circuit. This research reveals a sexually dimorphic regulation of synaptic plasticity in the BLA involving neuronal aromatase, which produces the neurosteroid 17?-estradiol (E2). As male and female neurons in rodent BLA responded differently to aromatase inhibition both in vivo and in vitro, our findings suggest that E2 signaling in BLA neurons is regulated sex-dependently, presumably via mechanisms that have been established during sexual determination. These findings could be relevant for the understanding of sex differences in mood disorders and of the side effects of cytochrome P450 aromatase inhibitors, which are frequently used for breast cancer therapy.

Dataset Information

Integrin-mediated regulation of synaptic morphology, transmission, and plasticity.

Publications

Integrin-mediated regulation of synaptic morphology, transmission, and plasticity.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets