Dopamine dendritic spines

Smiley, J. F., Levey, A. I., Ciliax, B. J. and Goldman-Rakic, P. S. D1 dopamine receptor immunoreactivity in human and monkey cerebral cortex predominant and extrasynaptic localization in dendritic spines. Proc. Natl Acad. Sci. U.S.A. 91 5720-5724,1994. 

Figure 1. Degenerating nerve ending (->) in guinea pig neostriatum following 6-OH-dopamine administration making asymmetrical synaptic contact with dendritic spine positively staining for cholineacetyltransferase (= ). Bar indicates 0.125 gm. (Reproduced with permission from Ref. 15. Copyright 1976, Elsevier Biomedical...

Scott L, Kruse MS, Forssberg H, Brismar H, Greengard P, et al. 2002. Selective up-regulation of dopamine Dl receptors in dendritic spines by NMDA receptor activation. Proc Natl Acad Sci USA 99 1661-1664. 

Thus, a GSH deficit has consequences consistent with the concept of functional disconnectivity, as hypofunction of NMDA-R and alteration of dopamine signaling have been observed. When imposed on animals during development, a GSH deficit induces also a structural disconnectivity, as revealed by the decrease in dendritic spines and parvalbumin-immunoreactivity of inhibitory intemeurons in the prefrontal cortex Finally, a transient GSH deficit during brain development causes deficits in visual recognition and olfactory integration. 

Fig. 1. A. Morphology of dopamine synapses. Electron micrograph of neostriatal section showing a TH-positive bouton in symmetrical synaptic contact (arrow) with a dendritic spine (S) which receives an asymmetrical synapse on its head from a bouton containing small round vesicles (asterisk) spine apparatus (small arrow). Scale bar 0.2 pm. From Fig. 2F of Freund et al. (1984), with permission. B. Three-dimensional reconstruction of a dopaminergic axon found in a series of 70 sections of the neostriatum, showing the distribution of synaptic sites (arrows). Scale bar 1.0 pm. Modified from Fig. 3C of Groves et al. (1994), with permission.

Spiny projection neurons receive inputs from the cortex, thalamus and amygdala, which make asymmetric synapses on dendritic spines, and to a lesser degree, dendritic shafts. These inputs provide the major excitatory input to these neurons. In addition, a number of inputs from outside the striatum, and from within the striatum provide inputs that function to modify the responsiveness of spiny neurons to the excitatory input. These include inputs from dopamine afferents from the substantia nigra, inhibitory GABA inputs from the axon collaterals of other spiny neurons, inhibitory inputs from GABA (and peptide containing) striatal interneurons, and inputs from cholinergic striatal interneurons. 

Lee, K. W, Y. Kim, A. M. Kim, K. Helmin, A. C. Naim, and P. Greengard. 2006. Cocaine-induced dendritic spine formation in D1 and D2 dopamine receptor-containing medium spiny neurons in nucleus accumbens. Proc. Natl Acad. Scl US 28 103(9) 3399-3404. 

Robinson and Kolb (1997) treated rats with amphetamine twice a day for 5 days a week for a total of 5 weeks with a dose that was gradually increased from 1 mg/kg to 8 mg/kg. Thirty-eight days later, they found lasting structural modifications in the nucleus accumbens and prefrontal cortex neurons, including increased length of dendrites and density of spines. In a microdialysis study, Weiss et al. (1997) treated rats with amphetamine (1.5 mg/kg injected twice a day for 14 days). Seven days after withdrawal, the animals continued to show a reduced dopamine release in the ventral striatum in response to stress. 

However, not every asymmetrical synapse has a dopamine input onto the same spine. The highest estimates of the fraction of spines that are innervated by dopamine come from Freund et al. (1984) who found that 39% of spines on reconstructed dendrites of a single striatonigral cell received one asymmetrical and one TH-positive symmetrical synapse. In contrast, estimates based on quantitative neuroanatomy, together with some assumptions about the distribution of synapses in the striatal volume give a much smaller fraction. Table 1 summarizes these estimates. 

Consistent with an extrasynaptic location of dopamine receptors, Huang et al. (1992) found D1 receptor labeling in the heads and the necks of spines, as well as in dendritic shafts at postsynaptic sites apposed to symmetric synapses. Similarly, Levey et al. (1993) found both D1 and D2 receptors localized in spiny dendrites and spine heads. Hersch et al. (1995) used subtype specific polyclonal and monoclonal antibodies to label D1 and D2 subtype receptors. Most prominently labeled were spiny dendrites with intense patches of submembranous label sometimes associated with symmetrical or asymmetrical... 

In parallel to the discovery of the long-term actions of dopamine on the sensitivity of the corticostriatal pathway, there have been a series of studies, which suggest that in the striatum, as in the hippocampus, the changes in synaptic strength have structural consequences. The earliest of these is probably the study of spine numbers in the neostriatum after destruction of dopamine input (Ingham et al., 1989). After a 6-OHDA lesion it seemed that there were fewer spines on individual dendrites in the striatum. The effect was visible as soon as the damage became stable at three weeks after the lesion and was still present one year later. But the lesion does not involve glutamatergic neurones. So perhaps the spines that are lost may have had dopamine synapses on them. That too seems unlikely since we estimated earlier that only about 11 % of spines would have a dopamine... 

Ultrastructural studies of the D5 dopamine receptor using immunocytochemistry have revealed that this receptor subtype is highly expressed in the human cortex in pyramidal neurons and their dendrites are present within layers IV-VI (Khan et al., 2000). The D5 dopamine receptor is also localized to the striatum, substantia nigra (both pars compacta and reticulata), the superior colliculus, the thalamus and the pyramidal cells of hippocampus (Khan et al., 2000). In the striatum, electron microscopic analysis indicates that D5 dopamine receptors are present in the spines where asymmetric synapses are formed... 

The ultrastructure of NA fibers of the cerebellar cortex and other parts of the rat CNS was analyzed with pre-embedding dopamine-y5-hydroxylase immunohistochemistry by Olschowka et al. (1981). Immunoreaction product was present in the axoplasm, associated with smooth endoplasmatic reticulum, Golgi apparatus, synaptic and large dense core vesicles and the outer membranes of mitochondria. Large varicosities were interconnected by narrow intervaricose axon segments. Varicosities, filled with clear, round synaptic vesicles and large dark-core vesicles, made asymmetric contacts with dendrites, but never with somata or axons. More than 50% of the labelled varicosities in the cerebellum made synaptic contacts most of them with dendritic shafts, fewer on spines. 

Fig. 9. Summary of the major synaptic inputs to spiny projection neurons. Inputs to the cell bod> arise mainly from striatal intemeurons. Inputs to proximal dendrites are mainly from striatal interneurons and other spiny projection neurons. Inputs to distal dendrites arise from extrastriatal sources, from the cortex (asymmetric/ glutamatergic) to the spine heads, from dopamine neurons in the midbrain (symmetric/dopamine) to the necks of spines and to interspine shafts. Other spiny projection neurons also provide symmetric inputs to the necks of spines and to interspine shafts.

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