RT Journal Article
SR Electronic
T1 Modulation of Rat Rotational Behavior by Direct Gene Transfer of Constitutively Active Protein Kinase C into Nigrostriatal Neurons
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4119
OP 4132
DO 10.1523/JNEUROSCI.18-11-04119.1998
VO 18
IS 11
A1 Song Song
A1 Yaming Wang
A1 Sun-Yung Bak
A1 Matthew J. During
A1 John Bryan
A1 Oliver Ashe
A1 Donna B. Ullrey
A1 Laura E. Trask
A1 Frederick D. Grant
A1 Karen L. O’Malley
A1 Heimo Riedel
A1 David S. Goldstein
A1 Kim A. Neve
A1 Gerald J. LaHoste
A1 John F. Marshall
A1 John W. Haycock
A1 Rachael L. Neve
A1 Alfred I. Geller
YR 1998
UL http://www.jneurosci.org/content/18/11/4119.abstract
AB The modulation of motor behavior by protein kinase C (PKC) signaling pathways in nigrostriatal neurons was examined by using a genetic intervention approach. Herpes simplex virus type 1 (HSV-1) vectors that encode a catalytic domain of rat PKCβII (PkcΔ) were developed. PkcΔ exhibited a constitutively active protein kinase activity with a substrate specificity similar to that of rat brain PKC. As demonstrated in cultured sympathetic neurons, PkcΔ caused a long-lasting, activation-dependent increase in neurotransmitter release. In the rat brain, microinjection of HSV-1 vectors that contain the tyrosine hydroxylase promoter targeted expression to dopaminergic nigrostriatal neurons. Expression of pkcΔ in a small percentage of nigrostriatal neurons (∼0.1–2%) was sufficient to produce a long-term (≥1 month) change in apomorphine-induced rotational behavior. Nigrostriatal neurons were the only catecholaminergic neurons that contained PkcΔ, and the amount of rotational behavior was correlated with the number of affected nigrostriatal neurons. The change in apomorphine-induced rotational behavior was blocked by a dopamine receptor antagonist (fluphenazine). D2-like dopamine receptor density was increased in those regions of the striatum innervated by the affected nigrostriatal neurons. Therefore, this strategy enabled the demonstration that a PKC pathway or PKC pathways in nigrostriatal neurons modulate apomorphine-induced rotational behavior, and altered dopaminergic transmission from nigrostriatal neurons appears to be the affected neuronal physiology responsible for the change in rotational behavior.