CommentaryDopaminergic signaling in dendritic spines
Section snippets
The central dopaminergic systems: an overview
Dopamine (DA) is a prototypical slow neurotransmitter that plays pivotal roles in a variety of cognitive, motivational, neuroendocrine, and motor functions [1], [2]. Two major groups of DA-containing neurons in the mammalian brain reside in the substantia nigra pars compacta (SN) and the ventral tegmental area (VTA) [3]. SN neurons form the nigrostriatal pathway, which projects mainly to the dorsal part of striatum where they control postural reflexes and initiation of movements. VTA neurons
Dendritic spines: sites of synaptic transmission, modulation and plasticity
Dendritic spines are small protrusions from the dendritic surface of neurons that are the major sites of excitatory synaptic transmission in the mammalian CNS [18], [19]. More than 90% of asymmetric glutamatergic synapses are made on the heads of dendritic spines, which in the hippocampus exhibit a near one-to-one relationship to excitatory synapses. Almost all spines belong to pyramidal neurons and mediate virtually all glutamatergic inputs to these cells, at least in the cortex. Spines
Dopaminergic innervation architecture
The midbrain DA systems project widely to a large number of postsynaptic target cells in multiple forebrain regions, including striatum, cortex, hippocampus, and amygdala. For example, in the striatum, which is the most densely innervated DA target, virtually every medium spiny neuron (MSN) is innervated by DA due to the extensive ramification of dopaminergic axons. This level of ramification gives rise to extraordinarily dense DA-releasing varicosities; the average distance between release
Dynamic trapping: a potential mechanism for DA receptor enrichment in spines?
Studies of a variety of neurotransmitter receptors have strengthened the view that receptor accumulation at synapses results from “dynamic trapping” of receptors by the submembranous PSD protein network [28]. The confinement of receptors, which are mobile even within synapses, may be achieved by the interactions with scaffolding proteins and other obstacles as well as by weak molecular interactions that act as steric hinderers or by inter-molecular attractive potentials. Single molecule
DA signaling in spines
Decades of investigation have elucidated a number of details concerning the molecular, cellular, biochemical, and pharmacological basis of DA signaling [1], [2], [4]. Direct assessment of DA signaling in spines, however, is essentially lacking. It is not known, for example, which second messenger systems are linked to DA receptors in spines and what signaling systems they engage. There are several fundamental obstacles that hinder direct assessments of these questions. First, DA transmission is
DA receptor-interacting proteins (DRIPs)
As mentioned previously, the mechanisms regulating DA receptor targeting, trafficking, and signaling in dendritic spines are largely unexplored. Recent studies, however, have identified a family of proteins that associate with different subtypes of DA receptors, which could help elucidate these underlying mechanisms.
As members of the seven-TM GPCR family, DA receptors reside in the plasma membrane with three extracellular and three intracellular loops (ILs) linking the seven TM domains (Fig. 3
Dendritic spine DA receptors: hypothetical models and behavioral implications
Dopaminergic terminal fibers form symmetric synapses on the neck of a subpopulation of dendritic spines. Although not all spines receiving a glutamate afferent are contacted by a DA varicosity, spines that do receive a DA afferent invariably receive an asymmetric glutamate input [17]. Thus, spines can be classified as diads or triads, based on whether or not they receive direct dopaminergic innervation. Both diads and triads can have three possible configurations based on the types of DA
Concluding remarks
DA receptors localized postsynaptically in dendritic spines may exert heterosynaptic influences on synaptic transmission and plasticity at the level of individual spines. This population of DA receptors may be particularly important in mediating the effect of DA in cognition, reward, and memory. The local rules governing DA receptor localization, trafficking, and anchorage in spines are poorly understood. The exact signaling cascades coupled to different DA receptors in dendritic spines also
Acknowledgements
We thank Ms. Donna Reed for her invaluable technical support. This work was supported by a National Center for Research Resources grant RR000168 (to the New England Primate Research Center), a National Institute of Neurological Disorders and Stroke grant NS057311 (W.-D.Y.), National Institute on Drug Abuse grants DA021420 (W.-D.Y.), DA011059, DA011928, DA017700, and DA024315 (R.D.S.), a National Alliance for Research on Schizophrenia and Depression Young Investigator Award, and Williams F.
References (95)
- et al.
Beyond the dopamine receptor: the DARPP-32/protein phosphatase-1 cascade
Neuron
(1999) - et al.
Paradoxical striatal cellular signaling responses to psychostimulants in hyperactive mice
J Biol Chem
(2006) - et al.
The principal features and mechanisms of dopamine modulation in the prefrontal cortex
Prog Neurobiol
(2004) - et al.
D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons
Trends Neurosci
(2007) - et al.
Dopamine-mediated regulation of corticostriatal synaptic plasticity
Trends Neurosci
(2007) - et al.
Immunocytochemical localization of D1 and D2 dopamine receptors in the basal ganglia of the rat: light and electron microscopy
Neuroscience
(1995) - et al.
Tyrosine hydroxylase-immunoreactive boutons in synaptic contact with identified striatonigral neurons, with particular reference to dendritic spines
Neuroscience
(1984) - et al.
Identification and verification of novel rodent postsynaptic density proteins
Mol Cell Proteomics
(2004) - et al.
Proteomics analysis of rat brain postsynaptic density: implications of the diverse protein functional groups for the integration of synaptic physiology
J Biol Chem
(2004) - et al.
Semiquantitative proteomic analysis of rat forebrain postsynaptic density fractions by mass spectrometry
J Biol Chem
(2004)
Surface trafficking of receptors between synaptic and extrasynaptic membranes: and yet they do move!
Trends Neurosci
Diffusional trapping of GluR1 AMPA receptors by input-specific synaptic activity
Neuron
Regulation of dopamine D1 receptor trafficking and desensitization by oligomerization with glutamate N-methyl-d-aspartate receptors
J Biol Chem
Modulation of D2R–NR2B interactions in response to cocaine
Neuron
Inhibition of the dopamine D1 receptor signaling by PSD-95
J Biol Chem
Anatomical and affinity state comparisons between dopamine D1 and D2 receptors in the rat central nervous system
Neuroscience
Getting formal with dopamine and reward
Neuron
Dopaminergic control of corticostriatal long-term synaptic depression in medium spiny neurons is mediated by cholinergic interneurons
Neuron
Association of the D2 dopamine receptor third cytoplasmic loop with spinophilin, a protein phosphatase-1-interacting protein
J Biol Chem
Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch
J Biol Chem
Dual regulation of NMDA receptor functions by direct protein–protein interactions with the dopamine D1 receptor
Cell
Coaggregation, cointernalization, and codesensitization of adenosine A2A receptors and dopamine D2 receptors
J Biol Chem
G protein-coupled receptors form stable complexes with inwardly rectifying potassium channels and adenylyl cyclase
J Biol Chem
Interaction of gamma-COP with a transport motif in the D1 receptor C-terminus
Eur J Cell Biol
Par-4 links dopamine signaling and depression
Cell
Identification of PSD-95 as a regulator of dopamine-mediated synaptic and behavioral plasticity
Neuron
Glutamate neurotoxicity and diseases of the nervous system
Neuron
Dopamine in neurotoxicity and neuroprotection: what do D2 receptors have to do with it?
Trends Neurosci
State-dependent mechanisms of LTP expression revealed by optical quantal analysis
Neuron
Memory and addiction: shared neural circuitry and molecular mechanisms
Neuron
A paradigm shift in brain research
Science
Dopamine-containing systems in the CNS
Dopamine receptors: from structure to function
Physiol Rev
Dopaminergic modulation of neuronal excitability in the striatum and nucleus accumbens
Annu Rev Neurosci
Desensitization of G protein-coupled receptors and neuronal functions
Annu Rev Neurosci
Localization of D1 and D2 dopamine receptors in brain with subtype-specific antibodies
Proc Natl Acad Sci USA
Electron microscopic analysis of D1 and D2 dopamine receptor proteins in the dorsal striatum and their synaptic relationships with motor corticostriatal afferents
J Neurosci
Regional, cellular, and subcellular variations in the distribution of D1 and D5 dopamine receptors in primate brain
J Neurosci
Synaptic relationships between dopaminergic afferents and cortical or thalamic input in the sensorimotor territory of the striatum in monkey
J Comp Neurol
Dopamine synaptic complex with pyramidal neurons in primate cerebral cortex
Proc Natl Acad Sci USA
Dendritic spines: cellular specializations imparting both stability and flexibility to synaptic function
Annu Rev Neurosci
Structure and function of dendritic spines
Annu Rev Physiol
Anatomical and physiological plasticity of dendritic spines
Annu Rev Neurosci
Signal-processing machines at the postsynaptic density
Science
PDZ domain proteins of synapses
Nat Rev Neurosci
Activity level controls postsynaptic composition and signaling via the ubiquitin–proteasome system
Nat Neurosci
The function of dendritic spines: devices subserving biochemical rather than electrical compartmentalization
J Neurosci
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