Hypothalamic sites responding to predator threats – the role of the dorsal premammillary nucleus in unconditioned and conditioned antipredatory defensive behavior

Abstract

In this study we provide a comprehensive analysis of the hypothalamic activation pattern during exposure to a live predator or an environment previously associated with a predator. Our results support the view that hypothalamic processing of the actual and the contextual predatory threats share the same circuit, in which the dorsal premammillary nucleus (PMd) plays a pivotal role in amplifying this processing. To further understand the role of the PMd in the circuit organizing antipredatory defensive behaviors, we studied rats with cytotoxic PMd lesions during cat exposure and examined the pattern of behavioral responses as well as how PMd lesions affect the neuronal activation of the systems engaged in predator detection, in contextual memory formation and in defensive behavioral responses. Next, we investigated how pharmacological blockade of the PMd interferes with the conditioned behavioral responses to a context previously associated with a predator, and how this blockade affects the activation pattern of periaqueductal gray (PAG) sites likely to organize the conditioned behavioral responses to the predatory context. Behavioral observations indicate that the PMd interferes with both unconditioned and conditioned antipredatory defensive behavior. Moreover, we have shown that the PMd influences the activation of its major projecting targets, i.e. the ventral part of the anteromedial thalamic nucleus which is likely to influence mnemonic processing, and PAG sites involved in the expression of antipredatory unconditioned and conditioned behavioral responses. Of particular relevance, this work provides evidence to elucidate the basic organization of the neural circuits integrating unconditioned and contextual conditioned responses to predatory threats.

New Perspectives on β-Adrenergic Mediation of Innate and Learned Fear Responses to Predator Odor

“…Next, we examined a possible neural substrate underlying the noradrenergic modulation of the defensive response to cat odor. Several studies have documented that the hypothalamus plays a major role in processing actual and contextual predatory threats and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats (Canteras et al, 1997Cezario et al, 2008;Staples et al, 2008). Interestingly, the PMd presents a moderately dense plexus of noradrenergic fibers (Moore and Card, 1984) and, therefore, is likely to be involved in the noradrenergic modulation of antipredatory defensive behavior.…”

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

“…Thus, LHAjd neurons may modulate directly the activity of a defensive behavior control system within the hypothalamus as well as extrahypothalamic components of this system located in the PAG. However, unlike the PMd, which appears to have an essential role in the expression of defensive responses (Blanchard et al, 2003(Blanchard et al, , 2005Canteras et al, 2008;Cezario et al, 2008;Motta et al, 2009), the role of the PAG is less certain; for example, defensive (and also grooming) responses have been reported to persist following extensive PAG lesion (Bagri et al, 1992;Van Erp et al, 1993).…”

“…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.…”

“…The regions selected for comparison were chosen for their relevance to this discussion, and the comparison is restricted to (the relatively few) studies that used PHA-L, described specific PAG inputs at multiple longitudinal levels, and plotted the data to the same rat brain map templates (Swanson, 2004) that were used in the current study. Thus, in Table 2 we present a cross-comparison of the PAG input from four LHA differentiations (LHAjd, LHAjp, LHAs, and LHAsf), and from three hypothalamic nuclei (and two parts of one of those nuclei) that have a central role in the control of reproductive/ sexual (MPN, VMHvl) (Bandler and Shipley, 1994;Behbehani, 1995;Coolen et al, 1996;Simerly, 2002) and defensive (VMHdm, PMd) Cezario et al, 2008;Santos et al, 2008) behaviors.Viewed in this way, a remarkable variety in the levels of convergence and divergence of PAG input is clearly apparent, and also the highly distinct topography of that input. Given the wide-ranging involvement of the PAG in somatic, autonomic, and neuroendocrine control, a high level of integration is perhaps unsurprising; however, a clearer picture of the structural underpinnings of that integration could be useful for gaining a deeper understanding of its functional dynamics.…”

Interação entre o grupamento parafacial/núcleo retrotrapezóide e a região de kölliker-fuse na modulação do padrão respiratório.

“…Em geral esses comandos podem ser gerados em áreas corticais superiores e recrutados de forma consciente durante manobras especiais, porém, o controle motor é essencialmente gerado de forma involuntária e, assim como a maioria dos comandos fundamentais para assegurar a sobrevivência ou integridade do indivíduo, são gerados ou modulados por estruturas subcorticais, localizadas no diencéfalo e/ou tronco encefálico (CEZARIO et al, 2008;SWANSON, 2000).…”