Archival ReportUncoupling the D1-N-Methyl-D-Aspartate (NMDA) Receptor Complex Promotes NMDA-Dependent Long-Term Potentiation and Working Memory
Section snippets
Primary Cell Culture
Hippocampal neurons from fetal (E18) Wistar rats were cultured as described previously (23). The cells were plated on glass coverslips coated with .1 mg/mL poly-d-lysine in borate buffer (25). The cultures were maintained by feeding twice a week by replacing half medium with fresh feeding medium. After 6 days of plating, 5 μmol/L Ara-C was added to stop the growth of glial cells.
Electrophysiology
Miniature excitatory postsynaptic currents (mEPSCs) were recorded from cultured hippocampal neurons 17 days after
Activation of D1R Upregulated NMDAR-Dependent LTP of mEPSCs in Hippocampal Neurons Through the D1–NR1 Direct Protein–Protein Interaction
The glycine-induced LTP model in hippocampal primary cultures is a validated model of LTP, similar to the electrically evoked EPSCs in CA1 neurons in hippocampal slices as previously described (23, 26, 28). Before determining the effect of D1R activation on synaptic activity, we used the glycine (200 μmol/L; 3 min) to validate our experimental system (data not shown). Once confirmed, we then tested whether activation of D1R can modulate mEPSC in hippocampal primary culture. SKF 81297 (10
Discussion
Consistent with previous studies demonstrating that D1R agonists stimulation increases LTP of field EPSPs (11, 35, 36), we have demonstrated that D1R stimulation can augment LTP of mEPSC in dissociated primary cultured rat hippocampal neurons in vitro. Moreover, we have shown that the D1R-induced increase in LTP is mediated by the D1R–NR1 interaction. Previous studies have suggested the involvement of both glutamate and dopamine in both LTP and in spatial working memory in the hippocampus (37,
References (79)
Memory and addiction: Shared neural circuitry and molecular mechanisms
Neuron
(2004)- et al.
Opposite modulation of cortical N-methyl-D-aspartate receptor-mediated responses by low and high concentrations of dopamine
Neuroscience
(1999) - et al.
Dual regulation of NMDA receptor functions by direct protein–protein interactions with the dopamine D1 receptor
Cell
(2002) - et al.
Tuning the engine of cognition: A focus on NMDA/D1 receptor interactions in prefrontal cortex
Brain Cogn
(2007) Dopamine: A potential substrate for synaptic plasticity and memory mechanisms
Prog Neurobiol
(2003)- et al.
Activation of PI3-kinase is required for AMPA receptor insertion during LTP of mEPSCs in cultured hippocampal neurons
Neuron
(2003) - et al.
Activation of synaptic NMDA receptors induces membrane insertion of new AMPA receptors and LTP in cultured hippocampal neurons
Neuron
(2001) - et al.
Synergistic requirements for the induction of dopaminergic D1/D5-receptor-mediated LTP in hippocampal slices of rat CA1 in vitro
Neuropharmacology
(2007) - et al.
Inactivation of NMDA receptors by direct interaction of calmodulin with the NR1 subunit
Cell
(1996) - et al.
Late-associativity, synaptic tagging, and the role of dopamine during LTP and LTD
Neurobiol Learn Mem
(2004)
The hippocampal-VTA loop: Controlling the entry of information into long-term memory
Neuron
Impairment of spatial but not contextual memory in CaMKII mutant mice with a selective loss of hippocampal LTP in the range of the theta frequency
Cell
Mice expressing activated CaMKII lack low frequency LTP and do not form stable place cells in the CA1 region of the hippocampus
Cell
Disruption of dendritic translation of CaMKIIalpha impairs stabilization of synaptic plasticity and memory consolidation
Neuron
CaMKII activation in the entorhinal cortex disrupts previously encoded spatial memory
Neuron
Reversible inhibition of CREB/ATF transcription factors in region CA1 of the dorsal hippocampus disrupts hippocampus-dependent spatial memory
Neuron
D1/5 receptor-mediated enhancement of LTP requires PKA, Src family kinases, and NR2B-containing NMDARs
Neuropharmacology
The cerebral cortex: A case for a common site of action of anti-psychotics
Tips
Mice with reduced NMDA receptor expression display behaviors related schizophrenia
Cell
Neurotransmitter aberrations in schizophrenia; new perspectives and therapeutic implications
Life Sci
Impaired spatial working memory but spared spatial reference memory following functional loss of NMDA receptors in the dentate gyrus
Eur J Neurosci
D1 but not D5 dopamine receptors are critical for LTP, spatial learning, and LTP-Induced arc and zif268 expression in the hippocampus
Cereb Cortex
Pathophysiologically based treatment interventions in schizophrenia
Nat Med
Mechanisms by which dopamine receptors may influence synaptic plasticity
Ann N Y Acad Sci
The NMDA/D1 receptor complex as a new target in drug development
Curr Top Med Chem
A dopamine/D1 receptor/protein kinase A/dopamine- and cAMP-regulated phosphoprotein (Mr 32 kDa)/protein phosphatase-1 pathway regulates dephosphorylation of the NMDA receptor
J Neurosci
Dopaminergic modulation of NMDA-induced whole cell currents in neostriatal neurons in slices: Contribution of calcium conductances
J Neurophysiol
Essential role of D1 but not D2 receptors in the NMDA receptor-dependent long-term potentiation at hippocampal-prefrontal cortex synapses in vivo
J Neurosci
D1/D5 receptor agonists induce a protein synthesis-dependent late potentiation in the CA1 region of the hippocampus
Proc Natl Acad Sci U S A
N-methyl-D-aspartate receptor blockade attenuates D1 dopamine receptor modulation of neuronal activity in rat substantia nigra
Synapse
Amphetamine and dopamine-induced immediate early gene expression in striatal neurons depends on postsynaptic NMDA receptors and calcium
J Neurosci
Effects of NMDA receptor antagonists on D1 dopamine receptor-mediated changes in striatal immediate early gene expression: Evidence for involvement of pharmacologically distinct NMDA receptors?
Dev Neurosci
Selective upregulation of dopamine D1 receptors in dendritic spines by NMDA receptor activation
Proc Natl Acad Sci U S A
Regulation of dopamine D1 receptor function by physical interaction with the NMDA receptors
J Neurosci
The missing link: A failure of fronto-hippocampal integration in schizophrenia
Nat Neurosci
Brain imaging in schizophrenia
Ann Rev Med
Calcium/calmodulin-dependent protein kinase II is associated with the N-methyl-D-aspartate receptor
Proc Natl Acad Sci U S A
The role of calmodulin as a signal integrator for synaptic plasticity
Nat Rev Neurosci
Relating neuronal nicotinic acetylcholine receptor subtypes defined by subunit composition and channel function
Mol Pharmacol
Cited by (73)
Neuronal lack of PDE7a disrupted working memory, spatial learning, and memory but facilitated cued fear memory in mice
2023, Progress in Neuro-Psychopharmacology and Biological PsychiatryCitation Excerpt :Thus, PDE7a has the unique capacity to regulate intracellular cAMP signaling related to the PDE8 x PKA-R complex, leading to marked cAMP signaling changes. PDE7a-nko mice demonstrated deficient cognitive functions, including working memory, episodic memory, long-term spatial learning & memory, and contextual fear memory, which is in agreement with deficient pCREB (Vandesquille et al., 2013), pCAMKK (Yang et al., 2009), p-eif2a (Chesnokova et al., 2017), p-ERK (Zhu et al., 2016), pAMPKa (Kobilo et al., 2014) or NR2A (Nai et al., 2010). Notably, deficient spatial learning in MWM became evident in PDE7a-nKO mice during the last two days of training similarly to their impaired performance in the DMP task, which likely reflects accumulating effect of PDE7a deficiency under such challenging conditions of daily training.
G protein-coupled purinergic P2Y receptor oligomerization: Pharmacological changes and dynamic regulation
2021, Biochemical PharmacologyHeteromerization of dopaminergic receptors in the brain: Pharmacological implications
2021, Pharmacological ResearchThe role of dopamine D1 receptors in MDMA-induced memory impairments
2020, Neurobiology of Learning and MemoryModulation and functions of dopamine receptor heteromers in drugs of abuse-induced adaptations
2019, NeuropharmacologyCitation Excerpt :It should be noted that the Tat-D1 peptide displayed, by itself, pro-locomotor effects (Shen et al., 2015a) and induced place-preference (Perreault et al., 2016; Hasbi et al., 2018). Importantly, the Tat-D1 peptide used to disrupt D1R/D2R interaction strongly overlaps with the so-called “Tat-D1R-t2 peptide” originally designed to block D1R/NMDAR heteromers (Nai et al., 2010; Ladepeche et al., 2013; see section 3.1). Furthermore, the Tat-D1R-t2 was shown to induce, by itself, ERK activation (Cahill et al., 2014b) and to potentiate glutamatergic synapses (Ladepeche et al., 2013), suggesting that this peptide could mimic D1R/NMDA interaction (see section 3.1), which could explain the pro-rewarding effect of the Tat-D1 peptide used by the George's group.
Authors QN, SL, and S-HW contributed equally to this work.