Optogenetic and chemogenetic approaches reveal differences in neuronal circuits that mediate initiation and maintenance of social interaction.

For social interaction to be successful, two conditions must be met: the motivation to initiate it and the ability to maintain it. This study uses both optogenetic and chemogenetic approaches to reveal the specific neural pathways that selectively influence those two social interaction components.

Distinct circuits in rat central amygdala for defensive behaviors evoked by socially signaled imminent versus remote danger.

Animals display a rich repertoire of defensive responses adequate to the threat proximity. In social species, these reactions can be additionally influenced by the behavior of fearful conspecifics. However, the majority of neuroscientific studies on socially triggered defensive responses focuses on one type of behavior, freezing. To study a broader range of socially triggered reactions and underlying mechanisms, we directly compared two experimental paradigms, mimicking occurrence of the imminent versus remote threat. Observation of a partner currently experiencing aversive stimulation evokes passive defensive responses in the observer rats. Similar interaction with a partner that has just undergone the aversive stimulation prompts animals to increase active exploration. Although the observers display behaviors similar to those of the aversively stimulated demonstrators, their reactions are not synchronized in time, suggesting that observers' responses are caused by the change in their affective state rather than mimicry. Using opsins targeted to behaviorally activated neurons, we tagged central amygdala (CeA) cells implicated in observers' responses to either imminent or remote threat and reactivated them during the exploration of a novel environment. The manipulation revealed that the two populations of CeA cells promote passive or active defensive responses, respectively. Further experiments confirmed that the two populations of cells at least partially differ in expression of molecular markers (protein kinase C-δ [PKC-δ] and corticotropin-releasing factor [CRF]) and connectivity patterns (receiving input from the basolateral amygdala or from the anterior insula). The results are consistent with the literature on single subjects' fear conditioning, suggesting that similar neuronal circuits control defensive responses in social and non-social contexts.

New insights into the intracellular distribution pattern of cationic amphiphilic drugs.

Cationic amphiphilic drugs (CADs) comprise a wide variety of different substance classes such as antidepressants, antipsychotics, and antiarrhythmics. It is well recognized that CADs accumulate in certain intracellular compartments leading to specific morphological changes of cells. So far, no adequate technique exists allowing for ultrastructural analysis of CAD in intact cells. Azidobupramine, a recently described multifunctional antidepressant analogue, allows for the first time to perform high-resolution studies of CADs on distribution pattern and morphological changes in intact cells. We showed here that the intracellular distribution pattern of azidobupramine strongly depends on drug concentration and exposure time. The mitochondrial compartment (mDsRed) and the late endo-lysosomal compartment (CD63-GFP) were the preferred localization sites at low to intermediate concentrations (i.e. 1 µM, 5 µM). In contrast, the autophagosomal compartment (LC3-GFP) can only be reached at high concentrations (10 µM) and long exposure times (72 hrs). At the morphological level, LC3-clustering became only prominent at high concentrations (10 µM), while changes in CD63 pattern already occurred at intermediate concentrations (5 µM). To our knowledge, this is the first study that establishes a link between intracellular CAD distribution pattern and morphological changes. Therewith, our results allow for gaining deeper understanding of intracellular effects of CADs.

Broader Autism Phenotype in Siblings of Children with ASD--A Review.

Although less pronounced, social, cognitive, and personality characteristics associated with autism spectrum disorders (ASD) may be present in people who do not meet ASD diagnostic criteria, especially in first-degree relatives of individuals with ASD. Research on these characteristics, referred to as broader autism phenotype (BAP), provides valuable data on potential expressions of autism-specific deficits in the context of family relations. This paper offers a review of research on BAP in siblings of individuals with ASD, focusing on reports regarding social, communication, and cognitive deficits, published from 1993 to 2014. The studies are divided into two groups based on participants' age: papers on preschool and older siblings of individuals with ASD; and publications on infants at risk for ASD. On the basis of this review, suggestions are offered for further research and its significance for our understanding of the genetic determinants of autism.