Contents lists available at ScienceDirect Behavioural Brain Research journal homepage: www.elsevier.com/locate/bbr Research report Influence of the anteromedial thalamus on social defeat-associated contextual fear memory Miguel J. Rangel Jr. a , Marcus Vinicius C. Baldo b , Newton Sabino Canteras a, ⁎ a Dept. Anatomy, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP 05508-000, Brazil b Dept. Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo,São Paulo, SP 05508-000, Brazil ARTICLE INFO Keywords: Contextual fear Social defeat Resident intruder paradigm Thalamic nuclei ABSTRACT The ventral part of the anteromedial thalamic nucleus (AMv) is heavily targeted by the dorsal premammillary nucleus (PMd), which is the main hypothalamic site that is responsive to both predator and conspecific aggressor threats. This PMd-AMv pathway is likely involved in modulating memory processing, and previous findings from our group have shown that cytotoxic lesions or pharmacological inactivation of the AMv drastically reduced contextual fear responses to predator-associated environments. In the present study, we investigated the role of the AMv in both unconditioned (i.e., fear responses during social defeat) and contextual fear responses (i.e., during exposure to a social defeat-associated context). We addressed this question by placing N-methyl-D-as- partate (NMDA) lesions in the AMv and testing unconditioned fear responses during social defeat and contextual fear responses during exposure to a social defeat-associated context. Accordingly, bilateral AMv lesions did not change unconditioned responses, but decreased contextual conditioning related to social defeat. Notably, our bilateral AMv lesions also included, to a certain degree, the nucleus reuniens (RE), but single RE lesions did not affect innate or contextual fear responses. Overall, our results support the idea that the AMv works as a critical hub, receiving massive inputs from a hypothalamic site that is largely responsive to social threats and trans- ferring social threat information to circuits involved in the processing of contextual fear memories. 1. Introduction Social interactions are essential for defining access to sexual part- ners, territories and nutritional resources [see 1]. The definition of social hierarchy is established aggressively, with different physiological and behavioral consequences for defeated animals and winners [2]. Defeated animals present clear defensive responses when re-exposed to a potential aggressor or to a context previously associated with a social defeat [3–7]. Studies conducted in our laboratory showed that defeated animals avoid cages in which they had been defeated and performed a careful exploration of the environment through risk as- sessment behaviors [7]. Importantly, social defeat has been proposed to be an animal model of depression [8], resulting in similar behavioral and neuroendocrine changes to those found in depressed patients [9]. Combining the results of behavioral, neuronal immediate early gene activation, lesion, and neuroanatomical experiments, we have deli- neated a putative circuit that is involved in both innate and contextual defense responses in a subordinate conspecific [7,10,11]. During social defeat, the dorsal premammillary nucleus (PMd) is the hypothalamic site that presents the most striking activation, which appears to be particularly confined to the dorsomedial part of the nucleus [10,11]. The dorsomedial part of the PMd receives strong inputs from specific regions of the lateral hypothalamic area (i.e., the juxtaparaventricular and juxtadorsomedial regions), which upregulate Fos expression during social defeat and likely convey septo-hippocampal information that encodes the environmental boundary restriction imposed by the pre- sence of a dominant aggressor [11]. Moreover, the dorsomedial part of the PMd is further influenced by the conspecific-responsive circuit of the medial zone of the hypothalamus (including the medial preoptic area, the ventrolateral part of the ventromedial nucleus and the ventral premammillary nucleus), which is also mobilized during social defeat and integrates conspecific cues conveyed by the medial amygdalar nucleus [10]. Interestingly, PMd lesions block the passive components of social defense (i.e., freezing and sustained on the back position), as seen during a confrontation with a dominant aggressor [10]. It is no- teworthy that the PMd is believed to influence the mnemonic processes related to contextual defensive responses [12,13] and likely involves the projection branch to the ventral part of the anteromedial nucleus (AMv) [14]. The anterior thalamic nuclei have been shown to support multiple https://doi.org/10.1016/j.bbr.2017.10.038 Received 8 September 2017; Received in revised form 19 October 2017; Accepted 31 October 2017 ⁎ Corresponding author at: Department of Anatomy Institute of Biomedical Sciences University of Sao Paulo Av. Lineu Prestes, 2415 CEP 05508-900 Sao Paulo, SP, Brazil. E-mail address: newton@icb.usp.br (N.S. Canteras). Behavioural Brain Research 339 (2018) 269–277 Available online 06 December 2017 0166-4328/ © 2017 Elsevier B.V. All rights reserved. T