The role of dopamine receptors in regulating the size of axonal arbors

Factors that regulate terminal arbor size of substantia nigra pars compacta (SNpc) neurons during development and after injury are not well understood . This study examined the role of dopamine receptors in regulating arbor si ze. Terminal arbors were examined in mice with targeted deletion of the D1 or D2 dopamine receptor [D1(-/-) and D2(-/-) mice, respectively]. Terminal trees were also examined after treatment with receptor blockers and after p artial SNpc lesions. Immunohistochemistry was performed, and the number of SNpc neurons and dopaminergic terminals in the striatum was estimated. The number of dopaminergic SNpc neurons were reduced in D1(-/-) and D2(-/-) mic e. Density of dopaminergic terminals was unchanged in D1(-/-) mice and incr eased in D2 (-/-) mice. Steady-state striatal DA and DOPAC levels revealed that dopamine activity was enhanced in D2(-/-) mice but reduced in D1(-/-) mice. Two months after partial SNpc lesions, striatal terminal density was normal in both wild-type and D1(-/-) mice but reduced in D2(-/-) mice. Administra tion of DA receptor antagonists resulted in larger terminal arbors in D1(-/ -) and wildtype mice, whereas D2(-/-) mice showed no change in terminal den sity. Functional blockade of the D2R during development or in the adult brain res ults in increased axonal sprouting. Partial SNpc lesions resulted in compen satory sprouting, only in mice with functional D2R. These results suggest t hat individual dopaminergic axons in D2(-/-) mice have reached maximal arbo r size. We conclude that the D2 receptor may play a role in modulating the extent of the terminal arbor of SNpc neurons.