A Dopaminergic Axon Lattice in the Striatum and Its Relationship with Cortical and Thalamic Terminals

Medical Research Council Anatomical Neuropharmacology Unit, Department of Pharmacology, University of Oxford, Oxford, United Kingdom.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 10/2008; 28(44):11221-30. DOI: 10.1523/JNEUROSCI.2780-08.2008
Source: PubMed


Interactions between glutamatergic corticostriatal afferents and dopaminergic nigrostriatal afferents are central to basal ganglia function. The thalamostriatal projection provides a glutamatergic innervation of similar magnitude to the corticostriatal projection. We tested the hypotheses that (1) thalamostriatal synapses have similar spatial relationships with dopaminergic axons as corticostriatal synapses do and (2) the spatial relationships between excitatory synapses and dopaminergic axons are selective associations. We examined at the electron microscopic level rat striatum immunolabeled to reveal vesicular glutamate transporters (VGluTs) 1 and 2, markers of corticostriatal and thalamostriatal terminals, respectively, together with tyrosine hydroxylase (TH) to reveal dopaminergic axons. Over 80% of VGluT-positive synapses were within 1 microm of a TH-positive axon and >40% were within 1 microm of a TH-positive synapse. Of structures postsynaptic to VGluT1- or VGluT2-positive terminals, 21 and 27%, respectively, were apposed by a TH-positive axon and about half of these made synaptic contact. When structures postsynaptic to VGluT-positive terminals and VGluT-positive terminals themselves were normalized for length of plasma membrane, the probability of them being apposed by, or in synaptic contact with, a TH-positive axon was similar to that of randomly selected structures. Extrapolation of the experimental data to more closely reflect the distribution in 3D reveals that all structures in the striatum are within approximately 1 microm of a TH-positive synapse. We conclude that (1) thalamostriatal synapses are in a position to be influenced by released dopamine to a similar degree as corticostriatal synapses are and (2) these associations arise from a nonselective dopaminergic axon lattice.

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    • "synaptosomes (Smith et al., 1994; Moss and Bolam, 2008; Lehéricy et al., 2012). ST synaptosomes have been reported to be predominately comprised of pre-synaptic NSDA axon terminals (Barrett et al., 2012). "
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    • "However, in contrast to the traditional view of inter-neuronal chemical excitatory synaptic transmission in which structural and functional specializations are observed at the postsynaptic domains, striatal dopaminergic transmission does not always require such level of postsynaptic structural specialization (Rice and Cragg, 2008; Fuxe et al., 2012). Instead, release occurs in a diffuse manner, DA receptors are extrasynaptic and ultrastructural studies on the extension and density of DA neuron axonal arborization in the striatum point to broad, intricate projections that cover vast areas (Pickel et al., 1981; Smith et al., 1994; Moss and Bolam, 2008; Matsuda et al., 2009). This diffusely spread mode of transmission (in contrast to localized, highly spatially restricted communication), is termed “volume transmission”, and is a feature of a number of transmitters such as acetylcholine, norepinephrine, DA and serotonin (Taber and Hurley, 2014). "
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    • "The post-synaptic cortical-induced excitatory responses are modulated by dopamine acting through a wide variety of pre-and/or post-synaptic mechanisms dependent on the type and localization of dopamine receptors and the physiological state of striatal MSNs (Gonon, 1997; Reynolds et al., 2001; Cragg and Rice, 2004; Surmeier et al., 2007; Rice and Cragg, 2008; Ma et al., 2012). Although the regulatory effects of dopamine on thalamic glutamatergic transmission have not been directly assessed, the similarity between the overall pattern of synaptic connectivity of non-CM/Pf thalamic and cortical terminals with MSNs (Moss and Bolam, 2008) suggests that these two pathways may be regulated in the same manner by nigrostriatal dopamine afferents (Figure 1). The dopaminergic modulation of corticostriatal transmission relies in part on the synaptic convergence of dopaminergic and cortical synapses on individual spines of striatal MSNs (Freund et al., 1984; Bolam and Smith, 1990; Smith et al., 1994) and/or pre-synaptic dopamine-mediated regulation of glutamate release from neighboring cortical terminals (Surmeier et al., 2007). "
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