Previous studies from our laboratory have documented that the medial hypothalamic defensive system is critically involved in processing actual and contextual predatory threats, and that the dorsal premammillary nucleus (PMd) represents the hypothalamic site most responsive to predatory threats. Anatomical findings suggest that the PMd is in a position to modulate memory processing through a projecting branch to specific thalamic nuclei, i.e., the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv). In the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual responses to predator-related cues) defensive behaviors. During cat exposure, all experimental groups exhibited intense defensive responses with the animals spending most of the time in the home cage displaying freezing behavior. However, during exposure to the environment previously associated with a cat, the animals with combined RE + AMv lesions, and to a lesser degree, animals with single AMv unilateral lesions, but not animals with single RE lesions, presented a reduction of contextual conditioned defensive responses. Overall, the present results provide clear evidence suggesting that the PMd’s main thalamic targets (i.e., the nucleus reuniens and the AMv) seem to be critically involved in the emotional memory processing related to predator cues.
Motivated responses such as feeding, reproductive and defensive behaviors are critically important in assuring the survival of the animal, as well as the species. Specifically, defensive reactions are displayed in situations of threat to the physical integrity or survival of the organism, such as predator confrontation and agonistic interactions with animals of the same species (Motta et al., 2009). Predator exposure and predator-derived odors can be highly effective stimuli for eliciting defensive reactions in laboratory rodents, and these have been largely used in neurobiological and behavioral studies of unconditioned and conditioned fear (Apfelbach et al., 2005 and Blanchard and Blanchard, 1988).
In this context, a number of studies have provided evidence to elucidate the hypothalamic circuits putatively involved in the integration and expression of innate and learned fear responses to predatory threat (Canteras et al., 1997, Cezario et al., 2008, Dielenberg et al., 2001 and Staples et al., 2005). These studies indicate that predator threats are processed by a distinct medial hypothalamic circuit formed by the anterior hypothalamic nucleus, the dorsomedial part of the ventromedial nucleus, and the dorsal premammillary nucleus – the so-called medial hypothalamic defensive system (Canteras, 2002). These studies further suggest that the dorsal premammillary nucleus (PMd) is one of the most responsive hypothalamic sites during exposure to a predator or its odor, and to a context previously associated with a predatory threat. In line with this view, lesions centered in the PMd severely reduce the defensive responses to both a live cat and its odor (Blanchard et al., 2003, Canteras et al., 1997 and Cezario et al., 2008). In addition, pharmacological inactivation of the PMd, immediately before the exposure to a context previously associated with a predator, was able to practically abolish the contextual conditioned responses (Canteras et al., 2008, Cezario et al., 2008 and Do Monte et al., 2008).
Anatomical and functional findings have proposed that descending projections from the PMd to the dorsolateral periaqueductal gray are critical for the expression of unconditioned defensive reactions during exposure to a predator or its odor, as well as contextual conditioned responses to an environment previously associated with a predator threat (Cezario et al., 2008). Moreover, recent studies have indicated that, besides mediating unconditioned and contextual conditioned responses, PMd projections may influence the mnemonic processes related to the contextual defensive responses to predator cues (Canteras et al., 2008 and Do Monte et al., 2008). In such studies, it has been demonstrated that beta-adrenoceptor (Do Monte et al., 2008) or NMDA receptor (Canteras et al., 2008) blockade in the PMd, prior to cat odor exposure, interferes with contextual conditioned responses to cat odor. It has been postulated that the PMd’s role in modulating memory processing would involve its projecting branch to two specific thalamic nuclei: the rostral half of the nucleus reuniens (RE) and the ventral part of the anteromedial nucleus (AMv) (Canteras and Swanson, 1992 and Risold et al., 1997). In addition, the rostral nucleus reuniens is also targeted by other elements of the medial hypothalamic defensive system, such as the anterior hypothalamic nucleus (Risold et al., 1994 and Risold et al., 1997). Therefore, in the present study, we investigated the role of these thalamic targets in both unconditioned (i.e., fear responses to predatory threat) and conditioned (i.e., contextual fear responses to predator-related cues) defensive behaviors.
