Functional differences between D1 and D5 revealed by high resolution imaging on live neurons
ABSTRACT The interaction between the dopaminergic and glutamatergic systems governs normal behavior and is perturbed in many psychiatric disorders including schizophrenia. Hypofunction of the D1 family of receptors, to which the D(1) and D(5) subtypes belong, is a typical feature of schizophrenia. Here we have used confocal live cell imaging of neurons to examine the distinct roles of the D(1) and D(5) receptors in the intra-neuronal interaction with the glutamatergic system. Using fluorescently tagged D(1) or D(5) expressed in cultured striatal neurons, we show that both receptor subtypes are primarily transported via lateral diffusion in the dendritic tree. D(1) is to a much larger extent than D(5) expressed in spines. D(1) is primarily expressed in the head whereas D(5) is largely localized to the neck of the spine. Activation of N-methyl-D-aspartic acid (NMDA) receptors slowed the diffusion rate and increased the number of D(1) positive spines, while no effect on D(5) diffusion or spine localization could be observed. The observed differences between D(1) and D(5) can be attributed to structural differences in the C-terminus and its capacity to interact with NMDA receptors and PSD-95. Identification of a unique role of D(1) for the intra-neuronal interaction between the dopaminergic and glutamatergic systems will have implications for the development of more specific treatments in many neuropsychiatric disorders.
Full-textDOI: · Available from: Sandeep Kumar, Jul 07, 2014
- SourceAvailable from: Albert Gjedde
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- "In this study we quantified cytoplasmic D5Rs and D5Rs overlaying the plasma membrane on pyramidal cell somas, large dendrites and spines in the CA1 hippocampus. However, the position of a receptor is not fixed, as receptors constantly move laterally in the plasma membrane (Borgdorff and Choquet, 2002; Tardin et al., 2003; Kruusmagi et al., 2009) or circulate between the cytoplasm and the plasma membrane (Vickery and von Zastrow, 1999; He et al., 2009). "
ABSTRACT: A state of low dopaminergic activity has been implicated in attention-deficit/hyperactivity disorder (ADHD). The clinical symptoms of ADHD include inattention, impulsivity and hyperactivity, as well as impaired learning; dopaminergic modulation of the functions in the hippocampus is important to both learning and memory. To determine dopamine receptor density in a well-established animal model for ADHD, we quantified the dopamine D5 receptors in the hippocampus in the spontaneously hypertensive rat. We used immunofluorescence microscopy and immunogold electron microscopy to quantify the dopamine D5 receptor density on CA1 pyramidal cell somas and dendrites and dendritic spines in stratum radiatum and stratum oriens. The density of the dopamine D5 receptors was significantly lower in the cytoplasm of pyramidal cell somas in the spontaneously hypertensive rat compared to the control, indicating a reduced reservoir for insertion of receptors into the plasma membrane. Dopamine receptors are important for long term potentiation and long term depression, hence the deficit may contribute to the learning difficulties in individuals with the diagnosis of ADHD.Neuroscience 03/2013; 242. DOI:10.1016/j.neuroscience.2013.03.036 · 3.33 Impact Factor
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- "Rather, D 5 -IR was equally prevalent in spines and dendritic shafts, and was found more commonly in axonal and glial profiles than D 1 -IR. A study of fluorescently tagged D 1 and D 5 receptors in striatal cultures has shown that both receptors are located in dendritic spines with D 1 receptor found in more spines than D 5 (Kruusmagi et al., 2009). "
ABSTRACT: The D1 family of dopamine receptors (D1R) play a critical role in modulating reward in the nucleus accumbens (NAc). A better understanding of how D1Rs modulate NAc function must take into account the contributions of the two D1R subtypes, D(1) and D(5). In order to determine how these two subtypes contribute to dopamine's actions in the NAc, we utilized subtype specific antibodies and immunoelectron microscopy to quantitatively determine the localization of D(1) and D(5) in the neuropil of the primate NAc. We found that D(1) was more commonly found in dendritic shafts and spines, while D(5) was more commonly found in axon terminals, preterminal axons and glial processes. However, D(5) is well positioned to play an important role in postsynaptic modulation of inputs onto NAc medium spiny neurons. Approximately one third of spines contained D(1) and one quarter contained D(5), and as we have previously observed in the prefrontal cortex (PFC) and amygdala, these receptors overlapped extensively in dendritic spines. Similarly, we found overlap of the two D1R in axon terminals in the NAc; however, here D(5) labeled the larger population of terminals and D(1) was found in a subpopulation of D(5) containing terminals. Given the higher affinity of D(5) for dopamine, this suggest that presynaptic modulation of inputs by dopamine may be more easily evoked than in PFC where D(1) is the dominate presynaptic receptor. Finally, we investigated differences between the NAc and the dorsal striatum. We found that in the caudate half of dendritic spines contain D(1), significantly more than in the NAc. This suggests differences in how receptor is translated and distributed in D(1) mRNA expressing medium spiny neurons in the NAc and caudate.Neuroscience 09/2010; 169(4):1557-66. DOI:10.1016/j.neuroscience.2010.06.025 · 3.33 Impact Factor