Comparative Ultrastructural Localization of the Glutamate Delta-1 Receptor Immunoreactivity between the Mouse and Monkey Striatum 公开
Hoover, Andrew (Spring 2020)
Abstract
Prior research has demonstrated the importance of Glutamate Delta (GluD) receptors, a ionotropic glutamate receptor family that does not express typical ligand-gated fast-current flow, in the development, maintenance and plasticity of synaptic microcircuits in the cerebellar cortex. Although GluD2 is the main GluD receptor subtype expressed in the cerebellum, GluD1 is widely distributed in the mammalian brain, particularly in forebrain regions including the striatum. Recent findings from our laboratories have shown that the knockout of GluD1 expression in striatal neurons elicits cognitive deficits and disrupts the anatomical and functional integrity of the thalamostriatal system in mice. To further interpret these observations and extend our understanding of GluD1 function to the human brain, a detailed understanding of the cellular, subcellular and subsynaptic localization of striatal GluD1in primates and rodents is needed.
At the light microscopic level, striatal GluD1 immunoreactivity displayed a patchy pattern of distribution that coincided with the striosome/matrix compartmentation, but in an opposite fashion between mice and monkeys. While GluD1 was more heavily expressed in the striosomes than the matrix in the monkey caudate nucleus, the opposite was found in the mouse dorsal striatum. At the electron microscopic level, GluD1 immunoreactivity was preferentially expressed in dendritic shafts (47.9 ± 1.2% of total labeled structures), followed by glia (37.7 ± 2.5%), and dendritic spines (14.3 ± 2.6%) in the matrix of the mouse striatum. This pattern was not statistically different from the distribution of labeling in both the striosome and matrix compartments of the monkey caudate nucleus, with the exception of a small amount of GluD1-poistive unmyelinated axons and axon terminals. Pre-embedding immunogold staining revealed perisynaptic GluD1 labeling at putative axo-dendritic and axo-spinous glutamatergic synapses, extrasynaptic GluD1 immunoreactivity and intracellular GluD1 labeling apposed to the external surface of mitochondria. These data provide a basic map needed to further elucidate the role of GluD1 at striatal glutamatergic synapses, but also suggest possible GluD1 functions at extrasynaptic neuronal, glial and mitochondrial sites.
Table of Contents
Table of Contents
Abstract.…………………………………………………………………………………………............1
1. Introduction..……………………………………………………………………………….......…...3
2. Materials and Methods..……………………………………………………………….…......…..5
2.1 Animals…………………………………………………………………………….........….5
2.2 Light Microscopy Immunocytochemistry……………………………………..…….5
2.3 Electron Microscopy Immunocytochemistry………………………………….……6
2.4 Light Microscopic Image Analysis...………………………………………….………8
2.5 Electron Microscope Image Analysis...………………………………………………9
2.6 Statistical Analysis…..…………………………………………………….....…………10
3. Results..………………………………………………………………………………….........…….11
3.1 GluD1 is Differentially Expressed in the Striosome vs Matrix
Network of Mice vs Monkeys..………................................………………………11
3.2 Ultrastructural Localization of GluD1 in the Striatum…….……………………12
3.3 Immunogold Localization of GluD1 in the Striatum...……………………….…14
4. Discussion. ……………………………………………………………………………........………16
4.1 Consistent Distribution of GluD1 in Neuronal Elements
Suggests a Common Function for the Receptor....………….……………………16
4.2 GluD1 Interactions with Thalamostriatal Afferents: A Potential Role for
Cerebellin and More in Primates?...…………………………………………………18
4.3 Potential GluD1 Expression in Mitochondria and Glia ..…………………….…19
4.4 Future Directions….………………………………………………..…………….......…20
Tables and Figures…...…………………………….………......……………………………….……23
Table 1 – Relevant Data on Monkeys Used in this Experiment……………………23
Table 2 – Relevant Data on Mice Used in this Experiment..….……………………24
Table 3 – Specific Antibody Information…..……………………………………………25
Figure 1 – Striosome/Matrix Compartmentation of GluD1 in the
Monkey and Mouse Striatum………………………………………………….26
Figure 2 – GluD1 Immunostaining in the Mouse Striatum..……………………….27
Figure 3 – GluD1-immunoreactive Elements in the Monkey Striatum…….……28
Figure 4 – Immunogold Localization of GluD1 in the Mouse Striatum…………29
Figure 5 – Relative Mean Percentages of the Total Number of
GluD1 Immunostained Elements in the Pre-Commissural
Dorsal Mouse Striatum..…….............................................……………30
Figure 6 – Relative Mean Percentages of the Total number of
GluD1 Immunostained Elements in the Pre-Commissural
Monkey Caudate……................................................……………………31
References.……………………………….........……………………………………………………….32
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