Dopamine D4 receptor-deficient mice display cortical hyperexcitability
The dopamine D4 receptor (D4R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has b...
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2001
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein http://hdl.handle.net/20.500.12110/paper_02706474_v21_n11_p3756_Rubinstein |
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paper:paper_02706474_v21_n11_p3756_Rubinstein2023-06-08T15:24:43Z Dopamine D4 receptor-deficient mice display cortical hyperexcitability Attention deficit hyperactivity disorder D4 receptor Dopamine Epilepsy Frontal cortex Glutamate dopamine 4 receptor 4 aminopyridine bicuculline convulsant agent dopamine dopamine 2 receptor dopamine 4 receptor Drd4 protein, mouse glutamic acid piperazine derivative sonepiprazole sulfonamide animal experiment animal model article attention deficit disorder brain cortex brain slice controlled study dopaminergic transmission drug receptor binding electrophysiology epilepsy frontal cortex mouse nerve excitability nonhuman priority journal pyramidal nerve cell synaptic transmission animal cell membrane potential chemically induced disorder dose response drug antagonism drug effect genetics immunohistochemistry in vitro study metabolism motor cortex mouse mutant nerve cell inhibition patch clamp pathophysiology seizure synaptosome 4-Aminopyridine Animals Bicuculline Cerebral Cortex Convulsants Dopamine Dose-Response Relationship, Drug Glutamic Acid Immunohistochemistry Membrane Potentials Mice Mice, Neurologic Mutants Motor Cortex Neural Inhibition Patch-Clamp Techniques Piperazines Presynaptic Terminals Pyramidal Cells Receptors, Dopamine D2 Receptors, Dopamine D4 Seizures Sulfonamides The dopamine D4 receptor (D4R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D4R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and clamp recordings were performed in cortical pyramidal neurons voltage-from wild-type and D4R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D4R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D4R can function as an inhibitory modulator of glutamate activity in the FC. 2001 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein http://hdl.handle.net/20.500.12110/paper_02706474_v21_n11_p3756_Rubinstein |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Attention deficit hyperactivity disorder D4 receptor Dopamine Epilepsy Frontal cortex Glutamate dopamine 4 receptor 4 aminopyridine bicuculline convulsant agent dopamine dopamine 2 receptor dopamine 4 receptor Drd4 protein, mouse glutamic acid piperazine derivative sonepiprazole sulfonamide animal experiment animal model article attention deficit disorder brain cortex brain slice controlled study dopaminergic transmission drug receptor binding electrophysiology epilepsy frontal cortex mouse nerve excitability nonhuman priority journal pyramidal nerve cell synaptic transmission animal cell membrane potential chemically induced disorder dose response drug antagonism drug effect genetics immunohistochemistry in vitro study metabolism motor cortex mouse mutant nerve cell inhibition patch clamp pathophysiology seizure synaptosome 4-Aminopyridine Animals Bicuculline Cerebral Cortex Convulsants Dopamine Dose-Response Relationship, Drug Glutamic Acid Immunohistochemistry Membrane Potentials Mice Mice, Neurologic Mutants Motor Cortex Neural Inhibition Patch-Clamp Techniques Piperazines Presynaptic Terminals Pyramidal Cells Receptors, Dopamine D2 Receptors, Dopamine D4 Seizures Sulfonamides |
| spellingShingle |
Attention deficit hyperactivity disorder D4 receptor Dopamine Epilepsy Frontal cortex Glutamate dopamine 4 receptor 4 aminopyridine bicuculline convulsant agent dopamine dopamine 2 receptor dopamine 4 receptor Drd4 protein, mouse glutamic acid piperazine derivative sonepiprazole sulfonamide animal experiment animal model article attention deficit disorder brain cortex brain slice controlled study dopaminergic transmission drug receptor binding electrophysiology epilepsy frontal cortex mouse nerve excitability nonhuman priority journal pyramidal nerve cell synaptic transmission animal cell membrane potential chemically induced disorder dose response drug antagonism drug effect genetics immunohistochemistry in vitro study metabolism motor cortex mouse mutant nerve cell inhibition patch clamp pathophysiology seizure synaptosome 4-Aminopyridine Animals Bicuculline Cerebral Cortex Convulsants Dopamine Dose-Response Relationship, Drug Glutamic Acid Immunohistochemistry Membrane Potentials Mice Mice, Neurologic Mutants Motor Cortex Neural Inhibition Patch-Clamp Techniques Piperazines Presynaptic Terminals Pyramidal Cells Receptors, Dopamine D2 Receptors, Dopamine D4 Seizures Sulfonamides Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| topic_facet |
Attention deficit hyperactivity disorder D4 receptor Dopamine Epilepsy Frontal cortex Glutamate dopamine 4 receptor 4 aminopyridine bicuculline convulsant agent dopamine dopamine 2 receptor dopamine 4 receptor Drd4 protein, mouse glutamic acid piperazine derivative sonepiprazole sulfonamide animal experiment animal model article attention deficit disorder brain cortex brain slice controlled study dopaminergic transmission drug receptor binding electrophysiology epilepsy frontal cortex mouse nerve excitability nonhuman priority journal pyramidal nerve cell synaptic transmission animal cell membrane potential chemically induced disorder dose response drug antagonism drug effect genetics immunohistochemistry in vitro study metabolism motor cortex mouse mutant nerve cell inhibition patch clamp pathophysiology seizure synaptosome 4-Aminopyridine Animals Bicuculline Cerebral Cortex Convulsants Dopamine Dose-Response Relationship, Drug Glutamic Acid Immunohistochemistry Membrane Potentials Mice Mice, Neurologic Mutants Motor Cortex Neural Inhibition Patch-Clamp Techniques Piperazines Presynaptic Terminals Pyramidal Cells Receptors, Dopamine D2 Receptors, Dopamine D4 Seizures Sulfonamides |
| description |
The dopamine D4 receptor (D4R) is predominantly expressed in the frontal cortex (FC), a brain region that receives dense input from midbrain dopamine (DA) neurons and is associated with cognitive and emotional processes. However, the physiological significance of this dopamine receptor subtype has been difficult to explore because of the slow development of D4R agonists and antagonists the selectivity and efficacy of which have been rigorously demonstrated in vivo. We have attempted to overcome this limitation by taking a multidimensional approach to the characterization of mice completely deficient in this receptor subtype. Electrophysiological current and clamp recordings were performed in cortical pyramidal neurons voltage-from wild-type and D4R-deficient mice. The frequency of spontaneous synaptic activity and the frequency and duration of paroxysmal discharges induced by epileptogenic agents were increased in mutant mice. Enhanced synaptic activity was also observed in brain slices of wild-type mice incubated in the presence of the selective D4R antagonist PNU-101387G. Consistent with greater electrophysiological activity, nerve terminal glutamate density associated with asymmetrical synaptic contacts within layer VI of the motor cortex was reduced in mutant neurons. Taken together, these results suggest that the D4R can function as an inhibitory modulator of glutamate activity in the FC. |
| title |
Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| title_short |
Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| title_full |
Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| title_fullStr |
Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| title_full_unstemmed |
Dopamine D4 receptor-deficient mice display cortical hyperexcitability |
| title_sort |
dopamine d4 receptor-deficient mice display cortical hyperexcitability |
| publishDate |
2001 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_02706474_v21_n11_p3756_Rubinstein http://hdl.handle.net/20.500.12110/paper_02706474_v21_n11_p3756_Rubinstein |
| _version_ |
1768541842721210368 |