N-methyl-D-aspartate-induced c-Fos expression is enhanced in the forebrainstructures related to emotion in Fyn-deficient mice

Fyn tyrosine kinase is thought to be involved in the control of neuronal in tracellular signal transduction elicited by neurotransmitter stimulation. E motional disorders, such as fearfulness in Fyn-deficient mice, prompted us to investigate the neural mechanisms that lead to defective emotional expre ssion by using functional neuroanatomical methods. In order to examine the reactivity of a specific neural network to excitatory neurotransmitter admi nistration, we mapped the distribution of c-Fos-immunoreactive neurons afte r administering N-methyl-D-aspartate (NMDA) to control and mutant mice at t he 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-defi ned 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-a mino-5-phosphonovaleric acid, a competitive NMDA antagonist, both in the co ntrol and the mutant mice. These findings suggest that the excitability of the projection system from the amygdala to the hypothalamus and midbrain, t he main pathways of emotional expression, is enhanced in Fyn-deficient mice . (C) 2001 Elsevier Science B.V. All rights reserved.