Recently we determined that activation of the tachykinin 2 (Tac2) pathway in the central amygdala (CeA) is necessary and sufficient for the modulation of fear memories. The Tac2 pathway includes the Tac2 gene, which encodes the neuropeptide neurokinin B and its corresponding receptor neurokinin 3 receptor (NK3R). In this study, using Tac2-cre and Tac2-GFP mice, we applied a combination of in vivo (optogenetics) and multiple in vitro techniques to further explore the mechanisms of action within the Tac2 pathway. In transgenic mice that express ChR2 solely in Tac2 neurons, in vivo optogenetic stimulation of CeA Tac2-expressing neurons during fear acquisition enhanced fear memory consolidation and drove action potential firing in vitro. In addition, Tac2-CeA neurons were shown to co-express striatal-enriched protein tyrosine phosphatase, which may have an important role in regulating Nk3R signaling during fear conditioning. These data extend our current understanding for the underlying mechanism(s) for the role of the Tac2 pathway in the regulation of fear memory, which may serve as a new therapeutic target in the treatment of fear-related disorders.

Over repeated reference conversational partners tend to converge on preferred terms or referential pacts. Autism spectrum disorders (ASD) are characterized by pragmatic difficulties that are best captured by less structured tasks. To this end we tested adults with ASD who did not have language or intellectual impairments, and neurotypical comparison participants in a referential communication task. Participants were directors, describing unlexicalized, complex novel stimuli over repeated rounds of interaction. Group comparisons with respect to referential efficiency showed that directors with ASD demonstrated typical lexical entrainment: they became faster over repeated rounds and used shortened referential forms. ASD and neurotypical groups did not differ with respect to the number of descriptors they provided or the number of exchanges needed for matchers to identify figures. Despite these similarities the ASD group was slightly slower overall. We examined partner-specific effects by manipulating the common ground shared with the matcher. As expected, neurotypical directors maintained referential precedents when speaking to the same matcher but not with a new matcher. Directors with ASD were qualitatively similar but displayed a less pronounced distinction between matchers. However, significant differences and different patterns of reference emerged over time; neurotypical directors incorporated the new matcher's contributions into descriptions, whereas directors with ASD were less likely to do so.

No abstract

Distinct regions and cell types in the anterolateral group of the bed nucleus of the stria terminalis (BNST ALG) act to modulate anxiety in opposing ways. A history of chronic stress increases anxiety-like behavior with lasting electrophysiological effects on the BNST ALG. However, the opposing circuits within the BNST ALG suggest that stress may have differential effects on the individual cell types that comprise these circuits to shift the balance to favor anxiogenesis. Yet, the effects of stress are generally examined by treating all neurons within a particular region of the BNST as a homologous population. We used patch-clamp electrophysiology and single-cell quantitative reverse transcriptase PCR (scRT-PCR) to determine how chronic shock stress (CSS) affects electrophysiological and neurochemical properties of Type I, Type II, and Type III neurons in the BNST ALG. We report that CSS resulted in changes in the input resistance, time constant, action potential waveform, and firing rate of Type III but not Type I or II neurons. Additionally, only the Type III neurons exhibited an increase in Crf mRNA and a decrease in striatal-enriched protein tyrosine phosphatase (Ptpn5) mRNA after CSS. In contrast, only non-Type III cells showed a reduction in calcium-permeable AMPA receptor (CP-AMPAR) current and changes in mRNA expression of genes encoding AMPA receptor subunits after CSS. Importantly, none of the effects of CSS observed were seen in all cell types. Our results suggest that Type III neurons play a unique role in the BNST ALG circuit and represent a population of CRF neurons particularly sensitive to chronic stress.

Background and Aims: Previous blood product exposures may result in the development of antibodies to human leukocyte antigens (HLA). Pediatric heart transplant recipients who have these antibodies experience increased morbidity and mortality after transplantation. In this study, our aims were to confirm the association of previous allogeneic blood product exposures with the formation of anti-HLA antibodies, determine which blood components pose the greatest risk of developing antibodies, and assess differences in outcomes after transplantation between patients who had anti-HLA antibodies and those who did not. Methods:This retrospective investigation included all children who underwent car-

No abstract

No abstract