In the present study, we focused on sexual attraction and the ACC, a region known to be associated in pain and pleasure . We found that the ACC is robustly activated in male mice after exposure to female mice, as demonstrated by Fos expression, and pharmacological inhibition of the ACC could reduce sexual attraction. Although the excitability of ACC pyramidal neurons was not altered, the excitatory synaptic transmission was enhanced after sexual attraction. By using transgenic fosGFP mice, we found that sexual attraction induced functional increases of presynaptic glutamate release to activated neurons in ACC slices. Our results demonstrate the critical role of the ACC in sexual attraction, and provide the first evidence for the cellular mechanism of the ACC neurons involved in the sexual attraction.
Evidence from animal studies indicates that the central supraspinal systems controlling sexual arousal are localized predominantly in the limbic system. The ACC has been implicated as an unique area for evoking affective state such as romantic love , and a PET imaging study showed that the ACC is specifically activated during the excitation phase of sexual stimuli in men . In the present study, we used Fos expression as a marker of functional activation of neurons in the ACC. We found that all layers except layer I are activated bilaterally in the ACC, suggesting that sexual attraction results in specific pattern of activation. The results are consistent with previous reports mapping the brain areas involved in sexual attraction [19, 28], and establish the critical roles of the ACC in the sexual behaviors. However, due to limitations in using Fos as a marker, future studies must be conducted to elucidate the exact inputs to and outputs from the ACC after activation by sexual attraction. The significance of the activation of the ACC is probably not on the perception of sexual stimulation, which is fulfilled by rodent olfactory systems. Rather, we propose that the activation of the ACC affects positive emotional state, leading to sexual behaviors. In favor of the role of the ACC in sexual attraction, we found that inactivation of the ACC by local infusion of muscimol reduced the interest of male mice to female mice.
How could the ACC neurons be activated by sexual attraction? Fos expression is due to the conversion of extracellular signals into early genomic activation, which indicates that a signal transduction event has taken place in those activated neurons. Therefore, we hypothesized that functional alterations occurred in the activated neurons in the ACC after sexual attraction. To test this, we used fosGFP mice, a useful tool able to link sensory stimulation in animals to functional neuroanatomy and electrophysiology. In brain slices, we could detect GFP signals and performed whole-cell patch clamp recordings in GFP-positive neurons. We found enhanced presynaptic glutamate release, as shown by decreased PPF and increased mEPSC frequency. However, postsynaptic response was unlikely to be altered, since no changes were observed in the response mediated by either AMPA or NMDA receptors. We propose that the increased presynaptic glutamate release is the main trigger for the activation of neurons in the ACC following sexual attraction. This raises two essential questions which will require further insight into the function of the ACC in sexual attraction: (1) what signal triggers the increased glutamate release? and (2), what are the functional consequences of Fos activation?
In sum, our results provide a first mouse electrophysiological model for studying the sexual attraction in forebrain areas. At a single cell level, we are able to demonstrate a long-lasting changes in glutamate mediated excitatory synaptic transmission within the ACC, a cortical region known to be critical for sexual desire, attraction, and romantic love in human imaging studies. The use of transgenic and gene knockout mice in future will provide powerful tools to explore cellular and molecular basis of key brain functions of human such as love, sex and attraction between man and woman.