Evidence of a Role for the Lateral Hypothalamic Area Juxtadorsomedial Region (LHAjd) in Defensive Behaviors Associated with Social Defeat

Abstract

Our understanding of the extrinsic connections of the lateral hypothalamic area (LHA) has deepened in recent years. In particular, a series of studies using neural pathway-tracing methods to investigate the macroconnections of histologically differentiated LHA regions, have revealed that the neural connections of these regions are substantially distinct, and have robust connections with neural circuits controlling survival behaviors. To begin testing functional associations suggested by the distinct LHA region neural connections, the present study has investigated the role of the LHA juxtadorsomedial region (LHAjd) in the control of social defeat (a socially-relevant defensive behavior). Male rats received bilateral cytotoxic lesions targeted to the LHAjd. A resident-intruder paradigm was then employed to investigate the effect of these lesions on defensive behavioral responses. Behavioral data were collected during three phases of testing: (1) pre-encounter habituation to testing context; (2) encounter with a dominant conspecific in the testing context; and (3) post-encounter context. Statistical analysis of behavioral measures revealed a significant decrease in risk assessment behaviors during post-encounter context testing in lesioned intruders compared to sham-lesioned and intact rats. However, changes in defensive behavioral measures during the habituation, or during resident-intruder encounters, did not reach significance. We discuss these data in relation to LHAjd (and neighboring LHA region) neural connections, and in relation to current advances in understanding of the neural control of defensive behaviors. A refined model for the neural circuits that are central to the control of socially-relevant defensive behaviors is outlined. We also consider possible broader implications of these data for disorders of behavioral control.

Macroscale intrinsic network architecture of the hypothalamus

“…For example, reproductive behavior involves the medial preoptic nucleus (MPN) lateral part, the ventromedial hypothalamic nucleus (VMH) ventrolateral part, and the PMv; defensive behavior involves the anterior hypothalamic nucleus, the VMH dorsomedial part, and the PMd. More recent evidence indicates defensive behavior may also involve the VMH central part (24) and the LHAjd (37). With one exception (PMv), all these regions are in HY2 M1/2 subsystem 1.2, consistent with an updated model ( Fig.…”

Neurobiology of maternal regulation of infant fear: the role of mesolimbic dopamine and its disruption by maltreatment

“…For example, unlike sensitive period pups, maternal presence during the post-sensitive period incorporated the LH, suggesting a more adult-like network engaged by social stimuli may have emerged in post-sensitive period pups. The LH sends critical information to VTA and is known to modulate networks based on social cues [95]. Also, in contrast to younger pups, the mother's presence failed to suppress the ventral striatum and rostral VTA during conditioning.…”

Survival circuits and risk assessment

“…Activation of the dorsomedial and lateral PAG during RA is accompanied by activation of the lateral hypothalamus and dorsal premammillary nucleus but not the hippocampal and septal areas that provide a major top-down input to the lateral hypothalamus [28*]. In addition to the lateral hypothalamus [37], the posterior hypothalamus may be involved in RA (in the form of novel object exploration) and may concurrently control the anxiety-related neuroendocrine stress response [38]. Consistent with the top-down control of the PAG by the amygdala in relation to freezing and flight, the basolateral amygdala appears to be involved in the generation of RA as measured by stretch-attend in the elevated plus-maze [39] and by the firing of one group of its cells during periods of hesitation or retreat, but not of escape [40*].…”