Role of the rostral dorsomedial column of the periaqueductal gray during social defeat in rats.

Previous studies showed that the dorsal premammillary nucleus of the hypothalamus (PMD) is involved in social passive defensive behaviors likely to be meditated by descending projections to the periaqueductal gray (PAG). We focused on the rostral dorsomedial PAG (rPAGdm) to reveal its putative neural mechanisms involved in mediating social defensive responses. By combining retrograde tracing and FOS expression analysis, we showed that in addition to the PMD, the rPAGdm is influenced by several brain sites active during social defeat. Next, we found that cytotoxic lesions of the rPAGdm drastically reduced passive defense and did not affect active defensive responses. We then examined the rPAGdm's projection pattern and found that the PAGdm projections are mostly restricted to midbrain sites, including the precommissural nucleus, different columns of the PAG, and the cuneiform nucleus (CUN). Also, we found decreased FOS expression in the caudal PAGdm, CUN, and PMD after the rPAGdm was lesioned. The results support that the rPAGdm mediates passive social defensive responses through ascending paths to prosencephalic circuits likely mediated by the CUN. This study provides further support for the role of the PAG in the modulation of behavioral responses by working as a unique hub for influencing prosencephalic sites during the mediation of aversive responses.

Failure of AAV retrograde tracer transduction in hypothalamic projections to the periaqueductal gray matter.

Connectomics is an important field of neuroscience that examines how neurons are connected and form functional circuits that underly the brain's functions. Conventional tracers based on dye have led to great advances in mapping these connections, and now, neurotropic viruses are contributing to connectomics. In this work, two retrograde adeno-associated virus failed to transduce in projections from hypothalamic neurons to periaqueductal gray matter (PAG) but worked well in cortical connections to PAG. One of this virus also marked a substantial amount of PAG efferent projections, therefore working as an anterograde tracer. We also used hydroxystilbamidine (FluoroGold™) as a gold standard in retrograde tracing for comparison with the projections shown by the retrograde virus. As determined in past works, FluoroGold™ shows connections from the hypothalamus and cortex to the PAG. Also, an anterograde AAV was compared with one of the retrograde AAV, which showed a similar pattern of axonal projections and terminal fields. Hence, although neurotropic viruses are revolutionizing connectomics and other areas, their mechanism, neurotropism, and cell invasion need to be addressed. Their use is a great challenge and requires further studies to clarify their interaction with the nervous system's cells.

Defensive behaviors and brain regional activation changes in rats confronting a snake.

In the present study, we examined behavioral and brain regional activation changes of rats). To a nonmammalian predator, a wild rattler snake (Crotalus durissus terrificus). Accordingly, during snake threat, rat subjects showed a striking and highly significant behavioral response of freezing, stretch attend, and, especially, spatial avoidance of this threat. The brain regional activation patterns for these rats were in broad outline similar to those of rats encountering other predator threats, showing Fos activation of sites in the amygdala, hypothalamus, and periaqueductal gray matter. In the amygdala, only the lateral nucleus showed significant activation, although the medial nucleus, highly responsive to olfaction, also showed higher activation. Importantly, the hypothalamus, in particular, was somewhat different, with significant Fos increases in the anterior and central parts of the ventromedial hypothalamic nucleus (VMH), in contrast to patterns of enhanced Fos expression in the dorsomedial VMH to cat predators, and in the ventrolateral VMH to an attacking conspecific. In addition, the juxtodorsalmedial region of the lateral hypothalamus showed enhanced Fos activation, where inputs from the septo-hippocampal system may suggest the potential involvement of hippocampal boundary cells in the very strong spatial avoidance of the snake and the area it occupied. Notably, these two hypothalamic paths appear to merge into the dorsomedial part of the dorsal premammillary nucleus and dorsomedial and lateral parts of the periaqueductal gray, all of which present significant increases in Fos expression and are likely to be critical for the expression of defensive behaviors in responses to the snake threat.

Restraint stress and social defeat: What they have in common.

Bob Blanchard was a great inspiration for our studies on the neural basis of social defense. In the present study, we compared the hypothalamic pattern of activation between social defeat and restraint stress. As important stress situations, both defeated and immobilized animals displayed a substantial increase in Fos in the parvicellular part of the paraventricular nucleus,mostly in the region that contains the CRH neurons. In addition, socially defeated animals, but not restrained animals, recruited elements of the medial hypothalamic conspecific-responsive circuit, a region also engaged in other forms of social behavior. Of particular interest, both defeated and immobilized animals presented a robust increase in Fos expression in specific regions of the lateral hypothalamic area (i.e., juxtaparaventricular and juxtadorsomedial regions) likely to convey septo-hippocampal information encoding the environmental boundary restriction observed in both forms of stress, and in the dorsomedial part of the dorsal premammillary nucleus which seems to work as a key player for the expression of, at least, part of the behavioral responses during both restraint and social defeat. These results indicate interesting commonalities between social defeat and restraint stress, suggesting, for the first time, a septo-hippocampal­hypothalamic path likely to respond to the environmental boundary restriction that may act as common stressor component for both types of stress. Moreover, the comparison of the neural circuits mediating physical restraint and social defense revealed a possible path for encoding the entrapment component during social confrontation.

Anxiolytic-like effects of rose oil inhalation on the elevated plus-maze test in rats.

The effect of rose oil inhalation (1.0%, 2.5%, and 5.0% w/w) on the elevated plus-maze (EPM) test was investigated in adult male rats and compared with the effect of diazepam (DZP) (1.0 and 2.0 mg/kg) administered intraperitoneally 30 min before testing. Exposure to rose oil produced an anxiolytic-like effect similar to DZP (anxiolytic reference drug). Thus, at some concentrations, rose oil significantly increased the number of visits to and time spent in the open arms of the EPM. Anxiolytic-like properties of rose oil were observed using the EPM, being consistent with other behavioral and clinical studies.