Dopamine Modulates Release from Corticostriatal Terminals

Abstract

Normal striatal function is dependent on the availability of synaptic dopamine to modulate neurotransmission. Within the striatum, excitatory inputs from cortical glutamatergic neurons and modulatory inputs from midbrain dopamine neurons converge onto dendritic spines of medium spiny neurons. In addition to dopamine receptors on medium spiny neurons, D2 receptors are also present on corticostriatal terminals, where they act to dampen striatal excitation. To determine the effect of dopamine depletion on corticostriatal activity, we used the styryl dye FM1-43 in combination with multiphoton confocal microscopy in slice preparations from dopaminedeficient (DD) and reserpine-treated mice. The activity-dependent release of FM1-43 out of corticostriatal terminals allows a measure of kinetics quantified by the halftime decay of fluorescence intensity. In DD, reserpine-treated, and control mice, exposure to the D2-like receptor agonist quinpirole revealed modulation of corticostriatal kinetics with depression of FM1-43 destaining. In DD and reserpinetreated mice, quinpirole decreased destaining to a greater extent, and at a lower dose, consistent with hypersensitive corticostriatal D2 receptors. Compared with controls, slices from DD mice did not react to amphetamine or to cocaine with dopamine-releasing striatal stimulation unless the animals were pretreated with L-3,4-dihydroxyphenylalanine (L-dopa). Electron microscopy and immunogold labeling for glutamate terminals within the striatum demonstrated that the observed differences in kinetics of corticostriatal terminals in DD mice were not attributable to aberrant cytoarchitecture or glutamate density. Microdialysis revealed that basal extracellular striatal glutamate was normal in DD mice. These data indicate that dopamine deficiency results in morphologically normal corticostriatal terminals with hypersensitive D2 receptors.

Dopamine is not Required for the Hyperlocomotor Response to NMDA Receptor Antagonists

“…Likewise, light and electron microscopic analysis of midbrain dopaminergic neurons, their projections, and target neurons in the striatum of DD mice has not revealed any gross differences compared to control mice (Zhou and Palmiter, 1995;Kim et al, 2002). In addition, the glutamatergic input to the striatum appears to be normal in that glutamate labeling in synaptic vesicles is normal, extracellular glutamate is normal as measured by microdialysis, and the kinetics of synaptic vesicle release from corticostriatal projections is normal in slice preparations (Bamford et al, 2004). The only difference noted thus far is that signaling via either D1 or D2 receptors is greatly enhanced in DD mice compared to controls, such that lower levels of dopamine or dopamine receptor agonists elicit maximal molecular or behavioral effects in DD mice (Kim et al, 2000(Kim et al, , 2002Robinson et al, 2004).…”

Striatal plasticity and medium spiny neuron dendritic remodeling in parkinsonism

“…A D 2 -like heteroceptor localized to the terminals of corticostriatal axons regulates release of glutamate from these striatal inputs [11]. Accordingly, the loss of the striatal dopamine innervation is accompanied by a removal of the dopamine D 2 -mediated inhibition on glutamate release.…”

Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine

“…We postulated that the inhibition may occur through the D2R-mediated presynaptic functions. However, D2Rs are expressed by striatal and cortical neurons (13,14) and DA neurons (5,15,16).…”