RESUMO
Neuron-Glia related cell adhesion molecule (NrCAM) is a candidate autism risk factor that promotes axon guidance through cytoskeletal linkages in developing brain but its role in limbic circuitry has not been investigated. In situ hybridization (ISH) and immunofluorescence staining showed that NrCAM is expressed in the developing amygdalar pathway of mouse embryos during outgrowth of projections in the stria terminalis, a major limbic tract that interconnects the central amygdala (CeA) with key targets in the bed nucleus of the stria terminalis (BNST). Analysis of fiber tracts in NrCAM mutant mice by Neurofilament protein immunohistochemistry showed pronounced defasciculation and misprojection of fibers in the ST. The defasciculation phenotype may result from impairment in NrCAM homophilic inter-axonal adhesion or axon repulsion from the secreted ligand Semaphorin 3F, which is expressed in limbic areas in proximity to the ST. Behavioral testing indicated that NrCAM null mice were impaired in context-dependent fear conditioning, in accord with altered amygdala-BNST connectivity, but displayed normal cued (tone-shock) conditioning. Results are consistent with the novel finding that NrCAM mediates fasciculation of axon fibers in the ST important for proper amygdalar-BNST circuitry and response to contextual fear conditioning.
RESUMO
Estradiol rapidly (within 30 minutes) influences a variety of sociosexual behaviors in both mammalian and nonmammalian vertebrates, including goldfish, in which it rapidly stimulates approach responses to the visual cues of females. Such rapid neuromodulatory effects are likely mediated via membrane-associated estrogen receptors; however, the localization and distribution of such receptors within the nervous system is not well described. To begin to address this gap, we identified GPER/GPR30, a G-protein-coupled estrogen receptor, in goldfish (Carassius auratus) neural tissue and used reverse-transcription polymerase chain reaction (RT-PCR) and in situ hybridization to test if GPR30 is expressed in the brain regions that might mediate visually guided social behaviors in males. We then used immunohistochemistry to determine whether GPR30 colocalizes with isotocin-producing cells in the preoptic area, a critical node in the highly conserved vertebrate social behavior network. We used quantitative (q)PCR to test whether GPR30 mRNA levels differ in males in breeding vs. nonbreeding condition and in males that were socially interacting with a female vs. a rival male. Our results show that GPR30 is expressed in the retina and in many brain regions that receive input from the retina and/or optic tectum, as well as in a few nodes in the social behavior network, including cell populations that produce isotocin. J. Comp. Neurol. 525:252-270, 2017. © 2016 Wiley Periodicals, Inc.
