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Identification of neuronal loci involved with displays of affective aggression in NC900 mice

Abstract

Aggression is a complex behavior that is essential for survival. Of the various forms of aggression, impulsive violent displays without prior planning or deliberation are referred to as affective aggression. Affective aggression is thought to be caused by aberrant perceptions of, and consequent responses to, threat. Understanding the neuronal networks that regulate affective aggression is pivotal to development of novel approaches to treat chronic affective aggression. Here, we provide a detailed anatomical map of neuronal activity in the forebrain of two inbred lines of mice that were selected for low (NC100) and high (NC900) affective aggression. Attack behavior was induced in male NC900 mice by exposure to an unfamiliar male in a novel environment. Forebrain maps of c-Fos+ nuclei, which are surrogates for neuronal activity during behavior, were then generated and analyzed. NC100 males rarely exhibited affective aggression in response to the same stimulus, thus their forebrain c-Fos maps were utilized to identify unique patterns of neuronal activity in NC900s. Quantitative results indicated robust differences in the distribution patterns and densities of c-Fos+ nuclei in distinct thalamic, subthalamic, and amygdaloid nuclei, together with unique patterns of neuronal activity in the nucleus accumbens and the frontal cortices. Our findings implicate these areas as foci regulating differential behavioral responses to an unfamiliar male in NC900 mice when expressing affective aggression. Based on the highly conserved patterns of connections and organization of neuronal limbic structures from mice to humans, we speculate that neuronal activities in analogous networks may be disrupted in humans prone to maladaptive affective aggression.

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Acknowledgments

Samina Ali, Mohamed Hammad, Blair Therit, and Raul Salinas provided excellent technical support. We thank Dr. Jean Lauder at UNC-Chapel Hill for use of her laboratory at the initial stages of this project. We thank Drs. Frank Longo and Rick Meeker for providing us with the use of their StereoInvestigator Software. We apologize to the large number of investigators whose primary work on this topic could not be cited due to space limitations. This work was supported by institutional funds to HTG.

Conflict of interest

The authors declare that they have no conflict of interest.

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Correspondence to H. Troy Ghashghaei.

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Nehrenberg, D.L., Sheikh, A. & Ghashghaei, H.T. Identification of neuronal loci involved with displays of affective aggression in NC900 mice. Brain Struct Funct 218, 1033–1049 (2013). https://doi.org/10.1007/s00429-012-0445-y

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Keywords

  • Aggression
  • Violence
  • Neuronal circuits
  • Neural networks
  • Neuronal activity
  • Amygdala
  • Nucleus accumbens
  • Hypothalamus
  • Limbic thalamus
  • Parafascicular thalamic nucleus
  • Paraventricular thalamic nucleus
  • Zona incerta
  • Anxiety disorders
  • Mouse
  • c-Fos