Neurons Expressing Fos-Like Protein Have a Special Functional Status in 
the Basal Ganglia 
The known biochemical anatomy of the striatum suggests that most of the 
neurons expressing Fos in response to psychomotor stimulants are in the 
class of striatal output neurons projecting into the movement-releasing 
pathways of the basal ganglia— the neurons expressing substance P-like 
tachykinin and dynorphin. Current models of the basal ganglia suggest that 
when these neurons are activated, thalamocortical pathways are disinhibited, 
and hence, regions of premotor cortex become active (Albin et al. 1989; 
Alexander and Crutcher 1990; Graybiel 1991a). Substance P/dynorphin- 
containing striatal output pathways also lead to the substantia nigra pars 
reticulata, which in turn results in disinhibition of the superior colliculus. By 
contrast, the enkephalinergic neurons are striatal output neurons that project 
into the pathway leading to the subthalamic nucleus, which is thought to 
decrease movement release by the basal ganglia. Thus, these two sets of 
neurons — those exhibiting an acute Fos response to psychomotor stimulant 
exposure and those not doing so — are thought to have antagonistic roles in 
movement control. The responsive neurons are thought to facilitate the 
occurrence of movements, whereas the nonresponsive neurons are thought 
to damp movements. It is not yet known whether the IEG response is related 
to, or paralleled by, changes in the membrane potential of the responsive 
neurons. If the transcription factor activation is correlated with neural activation, 
however, results on induction of Fos-like protein (Graybiel 1991b; Berretta et al., 
in press) would suggest the following hypothesis: that some of the activating 
properties of psychomotor stimulants could stem from an imbalance between 
the activation of movement-releasing and movement-inhibiting pathways of the 
basal ganglia. 
THE IEG RESPONSE ELICITED BY PSYCHOMOTOR STIMULANTS IS 
SELECTIVE TO SUBSETS OF lEGs 
The induction of lEGs in striatal neurons following acute exposure to cocaine 
and amphetamine is not limited to expression of c -fos, but findings to date 
suggest that the response is nevertheless selective (Moratalla et al. 1990, 
1991, submitted for publication; Cole et al. 1990). Judging from Northern 
blotting and in situ hybridization analysis, mRNAs corresponding to two of the 
lEGs of the fos/jun family so far tested, c -fos and jun- B, are strongly induced by 
cocaine and amphetamine. Although c -jun mRNA is often coordinately induced 
with c -fos, it is not induced by acute amphetamine or cocaine stimulation. 
Some other mRNAs of fos/jun genes are also unresponsive and are also not 
detectable by Northern blotting (Moratalla et al., submitted for publication). That 
other Fos-related antigens may be induced has been suggested by Young and 
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