Dissecting the brain's fear system reveals the hypothalamus is critical for responding in subordinate conspecific intruders

Abstract

Effective defense against natural threats in the environment is essential for the survival of individual animals. Thus, instinctive behavioral responses accompanied by fear have evolved to protect individuals from predators and from opponents of the same species (dominant conspecifics). While it has been suggested that all perceived environmental threats trigger the same set of innately determined defensive responses, we tested the alternate hypothesis that different stimuli may evoke differentiable behaviors supported by distinct neural circuitry. The results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments indicate that the hypothalamus is necessary for full expression of defensive behavioral responses in a subordinate conspecific, that lesions of the dorsal premammillary nucleus drastically reduce behavioral measures of fear in these animals, and that essentially separate hypothalamic circuitry supports defensive responses to a predator or a dominant conspecific. It is now clear that differentiable neural circuitry underlies defensive responses to fear conditioning associated with painful stimuli, predators, and dominant conspecifics and that the hypothalamus is an essential component of the circuitry for the latter two stimuli.defensive behavior ͉ dorsal premammillary nucleus ͉ periaqueductal gray A nimals have evolved a set of basic, genetically preprogrammed physiological responses and behaviors to ensure survival of individuals and of the species as a whole. Effective defense against threats in the environment is one obvious function essential for survival of the individual and is coordinated by the brain. A simple explanation is provided by the species-specific defensive reaction (SSDR) theory, which postulates that the same innately determined defensive behaviors (like freezing and flight) are triggered by all perceived environmental threats-from natural predators to electric foot shocks in a laboratory protocol (1). This seemingly limited response repertoire suggested the plausible hypothesis that an animal's defensive behavior system processes cues about predators and an artificial threat in the same way and has led to a unitary view of the neural network mediating fear responses, with the central amygdalar nucleus playing a critical role in linking fear processing and defensive responses (2). However, it is also possible that differentiable mechanisms are engaged. Animals are naturally selected to protect themselves from dangers associated with the presence of a predator or a dominant conspecific, which evokes the sensation of fear and associated behavioral responses (3), whereas it is reasonable to postulate that, in contrast, physically harmful stimuli alone may evoke pain with or without fear.Fear responses to predators or dominant conspecifics are comparable to other forms of goal-oriented behavior like feeding, drinking, and mating in the sense that they appear to be accompanied by strong motivation or drive followed by behaviors critical for maint...

Connections of the lateral hypothalamic area juxtadorsomedial region in the male rat

“…Nevertheless, the few previous pathway-tracing studies (Swanson, 1976;Conrad and Pfaff, 1976) are consistent with the present data, and a recent study indicating participation of the MPO in social defensive responses (Motta et al, 2009) is also consistent with a connectionindicated involvement of the LHAjd in the same. The conspicuous absence of definitive studies of the MPO and internuclear area reflects an issue that has, until recently, also applied to the LHA, namely, the absence of a definitive (at least provisionally) parcellation scheme.…”

“…4T-Y). In contrast to extensive investigations of the medial preoptic nucleus (MPN), only a few studies (and none recent) have provided a (partial) overview of the connections of the MPN-surrounding MPO (Swanson, 1976;Conrad and Pfaff, 1976), and none has specifically addressed MPO function.Nevertheless, the few previous pathway-tracing studies (Swanson, 1976;Conrad and Pfaff, 1976) are consistent with the present data, and a recent study indicating participation of the MPO in social defensive responses (Motta et al, 2009) is also consistent with a connectionindicated involvement of the LHAjd in the same. The conspicuous absence of definitive studies of the MPO and internuclear area reflects an issue that has, until recently, also applied to the LHA, namely, the absence of a definitive (at least provisionally) parcellation scheme.…”

“…Together these defined regions are considered to constitute a vital unit in the motor neuronal network that controls fundamental motivated behaviors (Swanson, 2000)-a motor neuronal network that is subject to voluntary regulation via descending input from the cerebral hemispheres. Recent work indicates that the PMd in particular appears to play a critical role in the control of defensive behavior (Blanchard et al, 2003(Blanchard et al, , 2005Cezario et al, 2008;Motta et al, 2009). Our present findings indicate that the LHAjd could also play a role in the control of defensive behavior through its robust connections with the medial hypothalamic zone defensive behavior system.…”

“…Our present data are consistent with the possibility that the LHAjd may also be integral to the control of defensive/ reproductive behavioral switching/coordination because it has direct connections with regions that have been indicated or suggested to be involved in the dual control of these behaviors (Choi et al, 2005;Sukikara et al, 2006Sukikara et al, , 2010. Thus, to recap, in addition to its connections with the PAG, VMHdm, and PMd, the LHAjd also has bidirectional connections with the medial nucleus of the amygdala (mostly input, from anterior and posterior parts), VMHvl (mostly input), and BSTpr.Furthermore, in a recent study the behavioral response and pattern of PMd and PAG Fos expression resulting from two different defensive behavior-eliciting stimuli (dominant conspecific and predator) was compared in adult male rats (Motta et al, 2009). In association with defensive behavioral responses that were consistent yet different for each stimulus, there was also a consistent yet different pattern of Fos expression in the PMd and PAG.…”

Connectivity‐based segmentation of the periaqueductal gray matter in human with brainstem optimized diffusion MRI

“…Hypothalamic and amygdala connectivity was modest when compared to the lPAG and vlPAG. This is in contrast to nonhuman studies in which some of the primary connections of the dlPAG arise from ventromedial hypothalamus via the amygdala [Motta et al, 2009]. Moreover, the spatial maps derived from the back‐projections, identified dominant vlPAG connectivity to the ventromedial hypothalamus, rather than the dlPAG [An et al, 1998].…”