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Ungerstedt, 1990) or a blockade of striatal dopamine receptors by neuroleptics (Meshul et al.,
1994).
In this way, Meshul et al. (2000) found that after one month following unilateral ablation
of the rat frontal cortex, removing corticostriatal input, or the injection of the neurotoxin 6-
OHDA, into the SNc, removing nigrostriatal input or a combined ipsilateral cortical and 6-
OHDA lesion (CTX/6-OHDA) a significant increase in all three lesion groups in the mean
percentage of asymmetrical synapses associated with a perforated postsynaptic density. They
suggest that following a CTX and/or 6-OHDA lesions, there is an increase in striatal
glutamatergic function. The large increase in the percentage of multiple synaptic boutons in
the combined lesion group suggests that dopamine or other factors released by the dopamine
terminals assist in regulating synapse formation. The same authors (Meshul et al., 1999)
reported that unilateral lesion of the rat nigrostriatal pathway with the neurotoxin 6-OHDA,
results in a time-dependent change in striatal glutamatergic function. One month following
the lesion, there is an increase in the extracellular level of striatal glutamate, as determined by
in vivo microdialysis. In addition, there is an increase in the mean percentage of striatal
asymmetrical nerve terminals associated with a perforated, or discontinuous, postsynaptic
density, a finding similar to that reported by Ingham et al. (1998). An increase in this
particular type of asymmetrical synaptic contact suggests an increase in activity of that
synaptic terminal (Greenough et al., 1978).
Increases in such synapses have been reported to be associated with increased neuronal
activity, as observed after the induction of long-term potentiation, hippocampal kindling, and
increases in neuronal input to the visual cortex (Geinisman et al., 1988; Geinisman et al.,
1991; Greenough et al., 1978; Meshul et al., 1994). Of interest is that the change in glutamate
synapses following a 6-OHDA lesion is primarily associated with alterations of the ipsilateral
corticostriatal pathway.
As we mentioned above, interactions between glutamate and dopamine occur both
presynaptically and postsynaptically within the striatum. These neurotransmitters act at
particular receptors on the pre and postsynaptic membranes. Striatal neurons, and nerve
terminals immediately afferent to them, contain both ionotropic (AMPA/kainate and N-
methyl-D-aspartate, NMDA, type) and metabotropic (mGluR family) glutamate receptors,
and D1-like (D1, D5 subtype) and D2-like (D2, D3 and D4 subtype) dopamine receptors. The
precise anatomical location and the degree of receptor subtype colocalisation on pre and
postsynaptic membranes are issues that remain particularly controversial (Gerfen et al., 1990;
Tarazi and Baldessarini, 1999). There are evidences that largely support a reciprocal
regulation of dopamine and glutamate release in the striatum, through NMDA receptor-
mediated augmentation and D2-like receptor-mediated reduction of neurotransmitter release
(Reynolds and Wickens, 2002).
A major form of interaction between glutamate and dopamine that occurs
postsynaptically at the level of individual spiny projection neurons is the modulation of
membrane excitability. This affects the probability that a spiny projection neuron will fire
action potentials in response to an excitatory event (Cepeda et al., 2001), thus dopamine is
seen as a modulator of corticostriatal synaptic transmission. It has been demonstrated that DA
depletion also appears to increase the excitability of MSN by diminishing the capacity of
these neurons to modulate intracellular calcium (Ca 2+ ) levels (Day et al., 2006).
Moreover, previous studies have demonstrated that a pathological form of synaptic
plasticity in the striatum related to supersensitivity of NMDA receptors could cause the
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