N-Methyl-D-aspartate-induced c-Fos expression is enhanced in the forebrain structures related to emotion in...

Fyn tyrosine kinase is thought to be involved in the control of neuronal intracellular signal transduction elicited by neurotransmitter stimulation. Emotional disorders, such as fearfulness in Fyn-deficient mice, prompted us to investigate the neural mechanisms that lead to defective emotional expression by using functional neuroanatomical methods. In order to examine the reactivity of a specific neural network to excitatory neurotransmitter administration, we mapped the distribution of c-Fos-immunoreactive neurons after administering N-methyl-D-aspartate (NMDA) to control and mutant mice at the subthreshold dose for seizure induction. The induction of neuronal c-Fos-immunoreactivity by NMDA was enhanced in the Fyn-deficient mice, and there was a much greater increase in immunopositive neurons in certain well-defined areas, such as the amygdaloid medial nuclear subdivisions, hypothalamic paraventricular nucleus, and midbrain periaqueductal gray, of the mutant. NMDA-induced c-Fos expression was attenuated by pretreatment with D-(-)-2-amino-5-phosphonovaleric acid, a competitive NMDA antagonist, both in the control and the mutant mice. These findings suggest that the excitability of the projection system from the amygdala to the hypothalamus and midbrain, the main pathways of emotional expression, is enhanced in Fyn-deficient mice.