Dynamics in brain activation and behaviour in acute and repeated social defensive motivated behaviour

In nature, confrontations between conspecifics are recurrent and related, in general, to the lack of resources such as food and territory. In this sense, adequate defence against a conspecific aggressor is essential for the individual’s survival and the group integrity. However, repeated social defeat is a significant stressor, promoting several behavioural changes, including on social defence per se. But what would be the neural basis of these behavioural changes? To explore some hypotheses about this, we investigated the effects of repeated social stress on neural circuits underlying the motivated behaviour social defence in male mice. The hypothalamus is an essential centre of these circuits. Different hypothalamic structures receive information about the conspecific from the medial amygdala and the bed nucleus of the terminal stria. Furthermore, the hypothalamus can receive environmental information via the septo-hippocampal-hypothalamic circuit. Both information is processed by the dorsal premammillary nucleus (PMD) and the ventrolateral portion of the ventromedial nucleus of the hypothalamus, which communicate with the periaqueductal grey, an important downstream site for behavioural emission. During our analysis, we observed that animals re-exposed three times to the aggressor spent more time in passive defence during their last exposure than in their first one. These animals also present a smaller mobilization of areas related to the processing of conspecific cues. In contrast, we did not observe changes in the PMD mobilization. Therefore, our data indicate that the balance between the activity of circuits related to conspecific processing and the PMD determines the pattern of social defence behaviour. Changes in this balance may be the basis of the adaptations in social defence after repeated social defeat.

VMH neurons under the magnifying glass

The ventromedial nucleus of the hypothalamus (VMH) is a complex brain structure that is integral to many neuroendocrine functions, including glucose regulation, thermogenesis, appetitive, social and sexual behaviours. As such, it is of little surprise that the nucleus is under intensive investigation to decipher the mechanisms which underlie these diverse roles. Developments in genetic and investigative tools, for example the targeting of steroidogenic factor-1-expressing neurons, have allowed us to take a closer look at the VMH, its connections and how it affects competing behaviours. In the current review, we aim to integrate recent findings into the literature and contemplate the conclusions that can be drawn.

Defective Autophagy in Sf1 Neurons Perturbs the Metabolic Response to Fasting and Causes Mitochondrial Dysfunction

ObjectiveThe ventromedial nucleus of the hypothalamus (VMH) is a critical component of the forebrain pathways that regulate energy homeostasis. It also plays an important role in the metabolic response to fasting. However, the mechanisms contributing to these physiological processes remain elusive. Autophagy is an evolutionarily conserved mechanism that maintains cellular homeostasis by turning over cellular components and providing nutrients to the cells during starvation. Here we investigated the importance of the autophagy-related gene Atg7 in Sf1-expressing neurons of the VMH in control and fasted conditions.MethodsWe generated Sf1-Cre; Atg7loxP/loxP mice and examined their metabolic and cellular response to fasting.ResultsFasting induces autophagy in the VMH, and mice lacking Atg7 in Sf1-expressing neurons display altered regulation in glucose and leptin homeostasis and impaired energy expenditure regulation in response to fasting. Moreover, loss of Atg7 in Sf1 neurons causes alterations in the central response to fasting. Furthermore, alterations in mitochondria morphology and activity are observed in mutant mice.ConclusionTogether, these data show that autophagy is nutritionally regulated in VMH neurons and that VMH autophagy participates in the control of energy homeostasis during fasting.