Lhx6 Delineates a Pathway Mediating Innate Reproductive Behaviors from the Amygdala to the Hypothalamus

Abstract

In mammals, innate reproductive and defensive behaviors are mediated by anatomically segregated connections between the amygdala and hypothalamus. This anatomic segregation poses the problem of how the brain integrates activity in these circuits when faced with conflicting stimuli eliciting such mutually exclusive behaviors. Using genetically encoded and conventional axonal tracers, we have found that the transcription factor Lhx6 delineates the reproductive branch of this pathway. Other Lhx proteins mark neurons in amygdalar nuclei implicated in defense. We have traced parallel projections from the posterior medial amygdala, activated by reproductive or defensive olfactory stimuli, respectively, to a point of convergence in the ventromedial hypothalamus. The opposite neurotransmitter phenotypes of these convergent projections suggest a "gate control" mechanism for the inhibition of reproductive behaviors by threatening stimuli. Our data therefore identify a potential neural substrate for integrating the influences of conflicting behavioral cues and a transcription factor family that may contribute to the development of this substrate.

Ventromedial hypothalamic nucleus lesions disrupt olfactory mate recognition and receptivity in female ferrets

“…This outcome corroborates our previous suggestion (Kelliher and Baum, 2001) that olfactory inputs take precedence over other sensory modalities in determining ferrets' sex partner preference. The present results are also consistent with the suggestion (Choi et al, 2005) that there is a neural circuit that includes the medial amygdala and the VMH which is selectively responsive to reproductively salient olfactory inputs. Indeed, body odors from male as opposed to female ferrets selectively augmented Fos expression in the VMH of female ferrets (Kelliher et al, 1998), and in the present study, lesioning of the VMH selectively reduced female ferrets' motivation to approach volatile odors emitted from male conspecifics.…”

“…Surgical removal of the VNO failed to disrupt the preference of female ferrets to approach odors emitted from anesthetized male vs female ferrets in Y-maze tests , further suggesting that mate recognition in this species relies on the processing of body odors via the main as opposed to the accessory olfactory system. A recent study using mice (Choi et al, 2005) suggests that the transcription factor Lhx6 delineates a neural circuit that conveys olfactory inputs of reproductive significance from the posterior dorsal medial amygdala to the ventromedial hypothalamic nucleus (VMH). Evidence of such an olfactory projection was previously obtained in estrous female ferrets (Wersinger and Baum, 1997) in which exposure to soiled male bedding augmented Fos expression in the main olfactory bulb as well as in several forebrain sites including the medial amygdala (MA), the bed nucleus of the stria terminalis (BNST), the medial preoptic area (MPOA) and the lateral border of the VMH.…”

Glutamate Microinjected in the Posterodorsal Medial Amygdala Induces Subtle Increase in the Consumption of a Three‐Choice Macronutrient Self‐Selection Diet in Male Rats

“…However, the influence of the MePD upon different hypothalamic nuclei that control neuroendocrine secretion or behavior display is far from simple. As evidenced by electrophysiological recordings, not all hypothalamic neurons sampled responded to MeA stimulation but, when it occurred, both excitatory and inhibitory responses were evoked in different target areas (Carrer et al, 1978;Choi et al, 2005;Bian et al, 2008). It is also conceivable that lesions involving the ''posterodorsal amygdala'' and that induced hyperphagia (King et al, 1998(King et al, , 1999(King et al, , 2003Rollins and King, 2000;Grundmann et al, 2005) have affected other amygdaloid nuclei or transition areas besides the MePD (Rollins and King, 2000;King et al, 2003;Moscarello et al, 2009).…”

“…Afferent excitatory pathways to this subnucleus use glutamate as neurotransmitter to code for primary or multimodal sensory information (Bian et al, 2008), probably relevant for the modulation of feeding behavior (McDonald, 1998;Berthoud, 2002). Besides, glutamate was found in almost 70% of all ejaculation-activated cells in the MePD (Simmons and Yahr, 2003), which could enhance the activity of efferent pathways that release gama-aminobutyric acid to inhibit or disinhibit specific hypothalamic targets and allow behavioral displays in rodents (Choi et al, 2005).…”

The main and the accessory olfactory systems interact in the control of mate recognition and sexual behavior

“…This result suggests that, in ArKO females, olfactory cues from a potential mate are correctly detected at the level of the olfactory bulb but that the integration of their reproductive value at the level of the amygdala and VMH is reduced, which may explain their deficits in the expression of sexual behavior [5]. Different patterns of Fos expression following exposure to urinary odors from conspecifics of both sexes were also observed in the amygdala of WT and ArKO males, a region that seems to be essential for the integration of olfactory stimuli in mice [20], suggesting that perinatal estrogens may be involved in the development of this brain area in both males and females. Finally, these results confirmed previously observed sex differences in neural activation of the accessory olfactory pathway following exposure to male odors [36], although no significant Fos responses were observed in central brain regions of male ArKO mice when exposed to male urine, suggesting that these sex differences probably reflect the perinatal actions of androgens as was recently suggested by the work of Bodo and Rissman [9].…”