An ultrastructural study of the neural circuit between the prefrontal cortex and the mediodorsal nucleus of the thalamus

Kuroda, Minpei; Yokofujita, Junko; Murakami, Kunio

doi:10.1016/s0301-0082(97)00070-1

Cited by 166 publications

(150 citation statements)

References 109 publications

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“…Both possibilities require further testing, yet the latter hypothesis is consistent with previous observations indicating that the removal of inhibitory GABA A tone in MD/CM nuclei increases c-fos expression and pyramidal discharge rate in PFC (18,25) as observed here with PCP. The involvement of thalamocortical inputs is also suggested by the increased c-fos expression produced by PCP in deep layer III/superficial layer V of PFC and layer IV of parietal cortex (N.S., P.C., G.M., and F.A., unpublished observations), which are target of inputs from MD onto PFC pyramidal neurons in the rat (26). Additionally, given the increase in vGluT1-positive cells expressing c-fos in the entorhinal cortex and its direct connectivity with PFC (27), this pathway cannot be excluded.…”

Section: Discussionmentioning

confidence: 92%

Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine

Kargieman

Santana²,

Mengod³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

158

169

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NMDA receptor (NMDA-R) antagonists are extensively used as schizophrenia models because of their ability to evoke positive and negative symptoms as well as cognitive deficits similar to those of the illness. Cognitive deficits in schizophrenia are associated with prefrontal cortex (PFC) abnormalities. These deficits are of particular interest because an early improvement in cognitive performance predicts a better long-term clinical outcome. Here, we examined the effect of the noncompetitive NMDA-R antagonist phencyclidine (PCP) on PFC function to understand the cellular and network elements involved in its schizomimetic actions. PCP induces a marked disruption of the activity of the PFC in the rat, increasing and decreasing the activity of 45% and 33% of the pyramidal neurons recorded, respectively (22% of the neurons were unaffected). Concurrently, PCP markedly reduced cortical synchrony in the delta frequency range (0.3-4 Hz) as assessed by recording local field potentials. The subsequent administration of the antipsychotic drugs haloperidol and clozapine reversed PCP effects on pyramidal cell firing and cortical synchronization. PCP increased c-fos expression in PFC pyramidal neurons, an effect prevented by the administration of clozapine. PCP also enhanced c-fos expression in the centromedial and mediodorsal (but not reticular) nuclei of the thalamus, suggesting the participation of enhanced thalamocortical excitatory inputs. These results shed light on the involvement of PFC in the schizomimetic action of NMDA-R antagonists and show that antipsychotic drugs may partly exert their therapeutic effect by normalizing a disrupted PFC activity, an effect that may add to subcortical dopamine receptor blockade.neuronal oscillations ͉ NMDA receptor antagonists ͉ schizophrenia ͉ delta frequency ͉ thalamus S chizophrenia is associated with alterations in several brain areas, including the thalamus, the hippocampus, the amygdala, and the prefrontal cortex (PFC), which are thought to underlie the deficits in working memory and executive functions exhibited by schizophrenic patients (1-3). Autopsy and neuroimaging studies have revealed the existence of a reduced PFC volume, reduced layer thickness, tight packing of pyramidal neurons and reduced neuropil in the brains of schizophrenic patients (1, 2, 4, 5). Moreover, alterations in key neurotransmitters such as glutamate, GABA, and dopamine have been reported in PFC (3,5,6).Noncompetitive N-methyl-D-aspartate (NMDA) receptor (NMDA-R) antagonists such as the dissociative anesthetics ketamine and phencyclidine (PCP), have been extensively used as pharmacological models of schizophrenia because of their ability to evoke positive and negative symptoms of schizophrenia as well as the characteristic cognitive deficits of the illness in humans (3, 7). Neuroimaging studies suggest that these effects are associated with an increased PFC activity (8). On the other hand, NMDA-R antagonists evoke a behavioral syndrome in experimental animals characterized by hyperlocomotion, stereoty...

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Section: Discussionmentioning

confidence: 92%

Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine

Kargieman

Santana²,

Mengod³

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

158

169

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“…What is the actual localization of these NMDA receptors and the source of the cortical hyperglutamatergic transmission induced by their blockade? Two of the well-known ascending glutamatergic inputs to the mPFC arise from the hippocampus (Carr and Sesack, 1996;Dégenètais et al, 2003) and the mediodorsal nucleus of the thalamus (Kuroda et al, 1998), and in both areas glutamatergic neurons are under the control of GABAergic cells (Gigg et al, 1994; Number of animals is given in parentheses. The control group received two injections (saline and vehicle) and, for the sake of clarity, is depicted as a dotted line.…”

Section: Discussionmentioning

confidence: 99%

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

López-Gil

Babot

Amargós-Bosch

et al. 2007

Neuropsychopharmacol

170

162

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The administration of noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists such as phencyclidine and ketamine has been shown to increase the extracellular concentration of glutamate and serotonin (5-HT) in the medial prefrontal cortex (mPFC). In the present work, we used in vivo microdialysis to examine the effects of the more potent noncompetitive NMDA receptor antagonist, MK-801, on the efflux of glutamate and 5-HT in the mPFC, and whether the MK-801-induced changes in the cortical efflux of both transmitters could be blocked by clozapine and haloperidol given systemically or intra-mPFC. The systemic, but not the local administration of MK-801, induced an increased efflux of 5-HT and glutamate, which suggests that the NMDA receptors responsible for these effects are located outside the mPFC, possibly in GABAergic neurons that tonically inhibit glutamatergic inputs to the mPFC. The MK-801-induced increases of extracellular glutamate and 5-HT were dependent on nerve impulse and the activation of mPFC AMPA/ kainate receptors as they were blocked by tetrodotoxin and NBQX, respectively. Clozapine and haloperidol blocked the MK-801-induced increase in glutamate, whereas only clozapine was able to block the increased efflux of 5-HT. The local effects of clozapine and haloperidol paralleled those observed after systemic administration, which emphasizes the relevance of the mPFC as a site of action of these antipsychotic drugs in offsetting the neurochemical effects of MK-801. The ability of clozapine to block excessive cortical 5-HT efflux elicited by MK-801 might be related to the superior efficacy of this drug in treating negative/cognitive symptoms of schizophrenia.

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“…Information transfer in the frontal cortical circuit is a crucial point for the forebrain neural loop through the cortex, basal ganglia, and thalamus, involved in the context-dependent release of various motor and cognitive circuits (Graybiel et al, 1994;Hikosaka et al, 2002). Therefore, it is important to know how these two types of corticostriatal cells are innervated by afferent fibers from the mediodorsal and parafascicular thalamic nuclei, areas that receive GABAergic inhibition from the basal ganglia (Kuroda et al, 1998;Cebrián et al, 2005). Thalamic fibers distribute in layer I and the deep part of layer II/III (Deschênes et al, 1996;Marini et al, 1996;Jones, 2001).…”

Section: Corticostriatal Cell Heterogeneity and Their Intracortical Cmentioning

confidence: 99%

“…Thalamic afferents innervate layer II/ III pyramidal cells in addition to layer V cells (Kuroda et al, 1998). Layer II/III pyramidal cells preferentially innervate thick tufted layer V pyramidal cells rather than slender layer V pyramidal cells (Thomson and Bannister, 1998;Thomson and Morris, 2002).…”

Section: Corticostriatal Cell Heterogeneity and Their Intracortical Cmentioning

confidence: 99%

Recurrent Connection Patterns of Corticostriatal Pyramidal Cells in Frontal Cortex

Morishima

Kawaguchi²

2006

J. Neurosci.

263

324

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An ultrastructural study of the neural circuit between the prefrontal cortex and the mediodorsal nucleus of the thalamus

Cited by 166 publications

References 109 publications

Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine

Antipsychotic drugs reverse the disruption in prefrontal cortex function produced by NMDA receptor blockade with phencyclidine

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

Recurrent Connection Patterns of Corticostriatal Pyramidal Cells in Frontal Cortex

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