 |
Previous Article | Next Article 
Journal of Neuroscience, Vol 15, 5222-5237, Copyright © 1995 by Society for Neuroscience
Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents
SM Hersch, BJ Ciliax, CA Gutekunst, HD Rees, CJ Heilman, KK Yung, JP Bolam, E Ince, H Yi and AI Levey
Department of Neurology, Emory University School of Medicine, Atlanta, Georgia 30322, USA.
The precise localization of D1 and D2 dopamine receptors within striatal
neurons and circuits is crucial information for further understanding
dopamine pharmacology. We have used subtype specific polyclonal and
monoclonal antibodies against D1 and D2 dopamine receptors to determine
their cellular and subcellular distributions, their colocalization, and
their differential connectivity with motor cortical afferents labeled
either by lesion-induced degeneration or by anterograde transport of
biotinylated dextrans. D1 and D2 are primarily expressed in medium-sized
neurons and spiny dendrites. Axon terminals containing D1 were rare whereas
D2-immunoreactive axon terminals forming symmetrical synapses with
dendrites and spines were common. In 2 microns sections, D1 was localized
to 53% of neurons, and D2 to 48% of neurons, while mixing D1 and D2
antibodies labeled 78%. By electron microscopy, D1 was localized to 43% of
dendrites and 38% of spines while D2 was localized to 38% of dendrites and
48% of spines. Combining D1 and D2 antibodies resulted in the labeling of
88.5% of dendrites and 92.6% of spines. Using different chromogens for D1
and D2, colocalization was not observed. Ipsilateral motor corticostriatal
afferents were primarily axospinous and significantly more synapsed with D1
than D2-positive spines (65% vs 47%). Contralateral motor corticostriatal
afferents were frequently axodendritic and no difference in their frequency
of synapses with D1 and D2 dendrites and spines was observed. These
findings demonstrate differential patterns of expression of D1 and D2
receptors in striatal neurons and axon terminals and their differential
involvement in motor corticostriatal circuits.
This article has been cited by other articles:

|
 |

|
 |
 
J. R. Glausier, Z. U. Khan, and E. C. Muly
Dopamine D1 and D5 Receptors Are Localized to Discrete Populations of Interneurons in Primate Prefrontal Cortex
Cereb Cortex,
November 19, 2008;
(2008)
bhn212v1.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Day, D. Wokosin, J. L. Plotkin, X. Tian, and D. J. Surmeier
Differential Excitability and Modulation of Striatal Medium Spiny Neuron Dendrites
J. Neurosci.,
November 5, 2008;
28(45):
11603 - 11614.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. S. Gertler, C. S. Chan, and D. J. Surmeier
Dichotomous Anatomical Properties of Adult Striatal Medium Spiny Neurons
J. Neurosci.,
October 22, 2008;
28(43):
10814 - 10824.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Zhang, P. Deng, Y. Ruan, and Z. C. Xu
Dopamine D1-Like Receptors Depress Excitatory Synaptic Transmissions in Striatal Neurons After Transient Forebrain Ischemia
Stroke,
August 1, 2008;
39(8):
2370 - 2376.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Kitaoka, T. Furuyashiki, A. Nishi, T. Shuto, S. Koyasu, T. Matsuoka, M. Miyasaka, P. Greengard, and S. Narumiya
Prostaglandin E2 Acts on EP1 Receptor and Amplifies Both Dopamine D1 and D2 Receptor Signaling in the Striatum
J. Neurosci.,
November 21, 2007;
27(47):
12900 - 12907.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Zhang, A. Vinuela, M. H. Neely, P. J. Hallett, S. G. N. Grant, G. M. Miller, O. Isacson, M. G. Caron, and W.-D. Yao
Inhibition of the Dopamine D1 Receptor Signaling by PSD-95
J. Biol. Chem.,
May 25, 2007;
282(21):
15778 - 15789.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Nadjar, J. M. Brotchie, C. Guigoni, Q. Li, S.-B. Zhou, G.-J. Wang, P. Ravenscroft, F. Georges, A. R. Crossman, and E. Bezard
Phenotype of Striatofugal Medium Spiny Neurons in Parkinsonian and Dyskinetic Nonhuman Primates: A Call for a Reappraisal of the Functional Organization of the Basal Ganglia.
J. Neurosci.,
August 23, 2006;
26(34):
8653 - 8661.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. J. Hallett, R. Spoelgen, B. T. Hyman, D. G. Standaert, and A. W. Dunah
Dopamine D1 activation potentiates striatal NMDA receptors by tyrosine phosphorylation-dependent subunit trafficking.
J. Neurosci.,
April 26, 2006;
26(17):
4690 - 4700.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. A. Olson, T. Tkatch, S. Hernandez-Lopez, S. Ulrich, E. Ilijic, E. Mugnaini, H. Zhang, I. Bezprozvanny, and D. J. Surmeier
G-Protein-Coupled Receptor Modulation of Striatal CaV1.3 L-Type Ca2+ Channels Is Dependent on a Shank-Binding Domain
J. Neurosci.,
February 2, 2005;
25(5):
1050 - 1062.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. S. Saklayen, O. S. Mabrouk, and E. A. Pehek
Negative Feedback Regulation of Nigrostriatal Dopamine Release: Mediation by Striatal D1 Receptors
J. Pharmacol. Exp. Ther.,
October 1, 2004;
311(1):
342 - 348.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Lei, Y. Jiao, N. Del Mar, and A. Reiner
Evidence for Differential Cortical Input to Direct Pathway versus Indirect Pathway Striatal Projection Neurons in Rats
J. Neurosci.,
September 22, 2004;
24(38):
8289 - 8299.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Gerfen
D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum Animal Model of Parkinson's Disease
Neuroscientist,
December 1, 2003;
9(6):
455 - 462.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
C. E. Junge, T. Sugawara, G. Mannaioni, S. Alagarsamy, P. J. Conn, D. J. Brat, P. H. Chan, and S. F. Traynelis
The contribution of protease-activated receptor 1 to neuronal damage caused by transient focal cerebral ischemia
PNAS,
October 28, 2003;
100(22):
13019 - 13024.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Sano, Y. Yasoshima, N. Matsushita, T. Kaneko, K. Kohno, I. Pastan, and K. Kobayashi
Conditional Ablation of Striatal Neuronal Types Containing Dopamine D2 Receptor Disturbs Coordination of Basal Ganglia Function
J. Neurosci.,
October 8, 2003;
23(27):
9078 - 9088.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S.-P. Onn, A. A. Fienberg, and A. A. Grace
Dopamine Modulation of Membrane Excitability in Striatal Spiny Neurons is Altered in DARPP-32 Knockout Mice
J. Pharmacol. Exp. Ther.,
September 1, 2003;
306(3):
870 - 879.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Iwamoto, S. Okumura, K. Iwatsubo, J.-I. Kawabe, K. Ohtsu, I. Sakai, Y. Hashimoto, A. Izumitani, K. Sango, K. Ajiki, et al.
Motor Dysfunction in Type 5 Adenylyl Cyclase-null Mice
J. Biol. Chem.,
May 2, 2003;
278(19):
16936 - 16940.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Ramanathan, J. J. Hanley, J.-M. Deniau, and J. P. Bolam
Synaptic Convergence of Motor and Somatosensory Cortical Afferents onto GABAergic Interneurons in the Rat Striatum
J. Neurosci.,
September 15, 2002;
22(18):
8158 - 8169.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. R. Gerfen, S. Miyachi, R. Paletzki, and P. Brown
D1 Dopamine Receptor Supersensitivity in the Dopamine-Depleted Striatum Results from a Switch in the Regulation of ERK1/2/MAP Kinase
J. Neurosci.,
June 15, 2002;
22(12):
5042 - 5054.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Herve, C. Le Moine, J.-C. Corvol, L. Belluscio, C. Ledent, A. A. Fienberg, M. Jaber, J.-M. Studler, and J.-A. Girault
G{alpha}olf Levels Are Regulated by Receptor Usage and Control Dopamine and Adenosine Action in the Striatum
J. Neurosci.,
June 15, 2001;
21(12):
4390 - 4399.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. E. Chapman, G. R. Hanson, R. P. Kesner, and K. A. Keefe
Long-Term Changes in Basal Ganglia Function after a Neurotoxic Regimen of Methamphetamine
J. Pharmacol. Exp. Ther.,
April 13, 2001;
296(2):
520 - 527.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
C. Cepeda, R. S. Hurst, K. L. Altemus, J. Flores-Hernandez, C. R. Calvert, E. S. Jokel, D. K. Grandy, M. J. Low, M. Rubinstein, M. A. Ariano, et al.
Facilitated Glutamatergic Transmission in the Striatum of D2 Dopamine Receptor-Deficient Mice
J Neurophysiol,
February 1, 2001;
85(2):
659 - 670.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Prou, W.-J. Gu, S. Le Crom, J.-D. Vincent, J. Salamero, and P. Vernier
Intracellular retention of the two isoforms of the D2 dopamine receptor promotes endoplasmic reticulum disruption
J. Cell Sci.,
January 10, 2001;
114(19):
3517 - 3527.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.N.D. Kerr and J. R. Wickens
Dopamine D-1/D-5 Receptor Activation Is Required for Long-Term Potentiation in the Rat Neostriatum In Vitro
J Neurophysiol,
January 1, 2001;
85(1):
117 - 124.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. J. LaHoste, B. L. Henry, and J. F. Marshall
Dopamine D1 Receptors Synergize with D2, But Not D3 or D4, Receptors in the Striatum without the Involvement of Action Potentials
J. Neurosci.,
September 1, 2000;
20(17):
6666 - 6671.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Svenningsson, M. Lindskog, C. Ledent, M. Parmentier, P. Greengard, B. B. Fredholm, and G. Fisone
Regulation of the phosphorylation of the dopamine- and cAMP-regulated phosphoprotein of 32 kDa in vivo by dopamine D1, dopamine D2, and adenosine A2A receptors
PNAS,
February 15, 2000;
97(4):
1856 - 1860.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Cai, H. Gurdal, C. Smith, H.-Y. Wang, and E. Friedman
Inverse Agonist Properties of Dopaminergic Antagonists at the D1A Dopamine Receptor: Uncoupling of the D1A Dopamine Receptor from Gs Protein
Mol. Pharmacol.,
November 1, 1999;
56(5):
989 - 996.
[Abstract]
[Full Text]
|
 |
|

|
 |

|
 |
 
L. J. M. J. Vanderschuren, G. Wardeh, T. J. De Vries, A. H. Mulder, and A. N. M. Schoffelmeer
Opposing Role of Dopamine D1 and D2 Receptors in Modulation of Rat Nucleus Accumbens Noradrenaline Release
J. Neurosci.,
May 15, 1999;
19(10):
4123 - 4131.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. G. Vickery and M. von Zastrow
Distinct Dynamin-dependent and -independent Mechanisms Target Structurally Homologous Dopamine Receptors to Different Endocytic Membranes
J. Cell Biol.,
January 11, 1999;
144(1):
31 - 43.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. C. Muly III, K. Szigeti, and P. S. Goldman-Rakic
D1 Receptor in Interneurons of Macaque Prefrontal Cortex: Distribution and Subcellular Localization
J. Neurosci.,
December 15, 1998;
18(24):
10553 - 10565.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. L. Waszczak, L. P. Martin, G. J. Greif, and J. E. Freedman
Expression of a dopamine D2 receptor-activated K+ channel on identified striatopallidal and striatonigral neurons
PNAS,
September 15, 1998;
95(19):
11440 - 11444.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Aosaki, K. Kiuchi, and Y. Kawaguchi
Dopamine D1-Like Receptor Activation Excites Rat Striatal Large Aspiny Neurons In Vitro
J. Neurosci.,
July 15, 1998;
18(14):
5180 - 5190.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Z. U. Khan, L. Mrzljak, A. Gutierrez, A. de la Calle, and P. S. Goldman-Rakic
Prominence of the dopamine D2 short isoform in dopaminergic pathways
PNAS,
June 23, 1998;
95(13):
7731 - 7736.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. A. Ingham, S. H. Hood, P. Taggart, and G. W. Arbuthnott
Plasticity of Synapses in the Rat Neostriatum after Unilateral Lesion of the Nigrostriatal Dopaminergic Pathway
J. Neurosci.,
June 15, 1998;
18(12):
4732 - 4743.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. P. Brandon, S. F. Logue, M. R. Adams, M. Qi, S. P. Sullivan, A. M. Matsumoto, D. M. Dorsa, J. M. Wehner, G. S. McKnight, and R. L. Idzerda
Defective Motor Behavior and Neural Gene Expression in RIIbeta -Protein Kinase A Mutant Mice
J. Neurosci.,
May 15, 1998;
18(10):
3639 - 3649.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Dumartin, I. Caille, F. Gonon, and B. Bloch
Internalization of D1 Dopamine Receptor in Striatal Neurons In Vivo as Evidence of Activation by Dopamine Agonists
J. Neurosci.,
March 1, 1998;
18(5):
1650 - 1661.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. MISSALE, S. R. NASH, S. W. ROBINSON, M. JABER, and M. G. CARON
Dopamine Receptors: From Structure to Function
Physiol Rev,
January 1, 1998;
78(1):
189 - 225.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Nishi, G. L. Snyder, and P. Greengard
Bidirectional Regulation of DARPP-32 Phosphorylation by Dopamine
J. Neurosci.,
November 1, 1997;
17(21):
8147 - 8155.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Bontempi and F. R. Sharp
Systemic Morphine-Induced Fos Protein in the Rat Striatum and Nucleus Accumbens Is Regulated by µ Opioid Receptors in the Substantia Nigra and Ventral Tegmental Area
J. Neurosci.,
November 1, 1997;
17(21):
8596 - 8612.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Le Moine, P. Svenningsson, B. B. Fredholm, and B. Bloch
Dopamine-Adenosine Interactions in the Striatum and the Globus Pallidus: Inhibition of Striatopallidal Neurons through Either D2 or A2A Receptors Enhances D1 Receptor-Mediated Effects on c-fos Expression
J. Neurosci.,
October 15, 1997;
17(20):
8038 - 8048.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Umemiya and L. A. Raymond
Dopaminergic Modulation of Excitatory Postsynaptic Currents in Rat Neostriatal Neurons
J Neurophysiol,
September 1, 1997;
78(3):
1248 - 1255.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
F. Gonon
Prolonged and Extrasynaptic Excitatory Action of Dopamine Mediated by D1 Receptors in the Rat Striatum In Vivo
J. Neurosci.,
August 1, 1997;
17(15):
5972 - 5978.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Harvey and M. G. Lacey
A Postsynaptic Interaction between Dopamine D1 and NMDA Receptors Promotes Presynaptic Inhibition in the Rat Nucleus Accumbens via Adenosine Release
J. Neurosci.,
July 15, 1997;
17(14):
5271 - 5280.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Berretta, H. B. Parthasarathy, and A. M. Graybiel
Local Release of GABAergic Inhibition in the Motor Cortex Induces Immediate-Early Gene Expression in Indirect Pathway Neurons of the Striatum
J. Neurosci.,
June 15, 1997;
17(12):
4752 - 4763.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. J. Surmeier, W.-J. Song, and Z. Yan
Coordinated Expression of Dopamine Receptors in Neostriatal Medium Spiny Neurons
J. Neurosci.,
October 15, 1996;
16(20):
6579 - 6591.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|