Biology Reference
In-Depth Information
S
YNAPTIC
P
LASTICITY
(LTP/LTD)
IN THE
D
ORSAL
S
TRIATUM
An important theme in research on drug addiction is to understand how the
neurochemical changes involving dopamine and glutamate can modify the pattern of synaptic
plasticity in the dorsal striatum. In other words, it is important to understand which
mechanisms of synaptic plasticity underlie long-lasting functional changes in the dorsal
striatum; moreover to study if abnormal synaptic plasticity can account for the progressive
loss of interest in natural rewards and the progressive inflexibility of the behavior that
resembles a compulsive disorder.
The cellular mechanisms of LTP and LTD can be evoked in the dorsal striatum. If the
afferent glutamatergic projections from the cortical regions to the dorsal striatum are activated
with a repetitive train of stimuli (tetanic stimulation, 100 Hz), the result is the reduction of the
size of the excitatory synaptic potentials (EPSP) in the striatal cells. That is, cortical
activation usually leads to long-term synaptic depression (LTD) and to a reduction in the
efficacy of the synaptic input to the striatal cells (Calabresi et al., 1992; Lovinger et al., 1993;
Wickens et al., 1996). The effects of applying dopamine in the dorsal striatum in brief pulses
in a manner similar to the release of dopamine from midbrain cells was also investigated. This
kind of dopaminergic activity is that which follows the presentation of a reward-related
stimulus in vivo. When dopamine application coincides with experimentally induced
presynaptic (cortical) and postsynaptic (striatal) activity, then the corticostrial synapses can
show a consistent increase in EPSP amplitude LTP. These results suggest that dopamine has
an enduring activity-dependent action on the efficacy of corticostriatal transmission to the
dorsal striatum. This activity may be a cellular basis for long-term changes in the nigrostriatal
system (Wickens et al., 1996). The involvement of dopamine in the cellular mechanisms of
long-term synaptic plasticity, LTD and LTP, in the dorsal striatum, has also been reported in
studies with denervated animals. Unilateral denervation of dopaminergic fibers projecting
from the midbrain SN to the striatum induced by homolateral injection of 6-hydroxydopamine
(6-OHDA) blocked LTP related to high-frequency stimulation (HFS) of corticostriatal fibers.
In the dorsal striatum, the induction of the LTP and LTD seems to require certain levels of
dopaminergic activity and the simultaneous activation of both glutamate or dopamine
receptors (Centonze et al., 1999). On the other hand, endogenous adenosine acting on
adenosime A1 receptors mediates the presynaptic inhibition at corticostriatal synapses, an
effect that is induced by a reduction of glutamate release. Presynaptic inhibition induced by
adenosine was antagonized by caffeine, a nonselective adenosine receptor antagonist
(Calabresi et al., 1997a)
Centonze et al. (2006) explored the effects of acute and chronic cocaine use in the
mechanisms of LTP and LTD at corticostriatal synapses. Cocaine treatment induced a
significant rewarding effect measured as conditioned place preference. High-frequency
stimulation of the corticostriatal projections induced LTP after 1 day of cocaine treatment and
after 7 days of cocaine administration. The same results were obtained in animals treated with
saline. However, saline treated rats were able to reverse LTP after 10 mins of low-frequency
stimulation of corticostriatal afferents, whereas cocaine treated rodents did not. In
physiological conditions, the ability to reverse LTP at striatal synapses functions as a
mechanism to “forget” maladaptive habits (Picconi et al., 2003), and the lack of ability to
reverse LTP may have important consequences in the drug addiction. To reverse LTP in the
