scholarly journals Pharmacological Discrimination of Effects of MK801 on Thalamocortical, Mesothalamic, and Mesocortical Transmissions

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 746 ◽  
Author(s):  
Okada ◽  
Fukuyama ◽  
Nakano ◽  
Ueda
Keyword(s):  
Prefrontal Cortex ◽  
Glutamate Receptor ◽  
Thalamic Nucleus ◽  
Glutamate Release ◽  
Gaba Release ◽  
Serotonin Release ◽  
Reticular Thalamic Nucleus ◽  
Thalamic Nuclei ◽  
Monoamine Release ◽  
Mediodorsal Thalamic Nucleus

N-methyl-d-aspartate/glutamate receptor (NMDAR) is one of the major voltage-sensitive ligand-gated cation channel. Several noncompetitive NMDAR antagonists contribute to pathophysiology of schizophrenia and mood disorders; however, the effects of inhibition of NMDAR on several transmitter system have not been well clarified. Thus, this study determined the selective NMDAR antagonist, MK801 (dizocilpine), on thalamocortical, mesothalamic, and mesocortical transmissions associated with l-glutamate, GABA, serotonin, norepinephrine, and dopamine using multiprobe microdialysis. Perfusion with MK801 into the medial prefrontal cortex (mPFC) increased and decreased respective regional releases of monoamine and GABA without affecting l-glutamate. The mPFC MK801-induced monoamine release is generated by the regional GABAergic disinhibition. Perfusion with MK801 into the reticular thalamic nucleus (RTN) decreased GABA release in the mediodorsal thalamic nucleus (MDTN) but increased releases of l-glutamate and catecholamine without affecting serotonin in the mPFC. The RTN MK801-induced l-glutamate release in the mPFC was generated by GABAergic disinhibition in the MDTN, but RTN MK801-induced catecholamine release in the mPFC was generated by activation of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate/glutamate receptor (AMPAR) which received l-glutamate release from thalamocortical glutamatergic terminals in the mPFC. Perfusion with MK801 into the dorsal raphe nucleus (DRN) decreased GABA release in the DRN but selectively increased serotonin release in the MDTN and mPFC. These DRN MK801-induced serotonin releases in the both mPFC and MDTN were also generated by GABAergic disinhibition in the DRN. These results indicate that the GABAergic disinhibition induced by NMDAR inhibition plays important roles in the MK801-induced releases of l-glutamate and monoamine in thalamic nuclei and cortex.

Comparison of Oculomotor Neuronal Activity in Paralaminar and Mediodorsal Thalamus in the Rhesus Monkey

2005 ◽  
Vol 93 (1) ◽  
pp. 614-619 ◽  
Author(s):  
Ikuo Tanibuchi ◽  
Patricia S. Goldman-Rakic
Keyword(s):  
Thalamic Nucleus ◽  
Delayed Response ◽  
Thalamic Nuclei ◽  
Related Activity ◽  
Dorsal Thalamus ◽  
Mediodorsal Thalamic Nucleus ◽  
Picture Stimuli ◽  
Fixation Task ◽  
Response Task ◽  
Lateral Nucleus

We previously reported that neurons in the mediodorsal thalamic nucleus (MD) are topographically organized and express spatial and nonspatial coding properties similar to those of the prefrontal areas with which they are connected. In the course of mapping the dorsal thalamus, we also studied neurons in a subset of thalamic nuclei (the caudal part of the ventral lateral nucleus (VLc), the oral part of the ventral posterior lateral nucleus (VPLo), the parvocellular part of the ventral anterior nucleus (VApc)) lateral to the MD and just across the internal medullary lamina. We compared these “paralaminar” neurons to MD neurons by having monkeys perform the same spatial and nonspatial cognitive tasks as those used to investigate the MD; these included two saccadic tasks—one requiring delayed and the other immediate responses—and one picture fixation task. Of the paralaminar thalamic neurons modulated by the saccadic tasks, a majority had saccade-related activity, and this was nearly always spatially tuned. Also, for about half of these neurons, the saccade-related activity occurred exclusively during the delayed-response task. No neurons with event-related activity in the saccadic tasks were preferentially modulated by specific picture stimuli, although other neurons were. All of these results were similar to what we had found for MD neurons. However, in contrast to the high proportion of presaccadic responses observed in the MD, the majority of saccade-related neurons in paralaminar thalamus exhibited mid- or postsaccadic activity, i.e., that started during or after the saccade. Our findings suggest that neurons in the paralaminar thalamus may be possible conduits of oculomotor feedback signals, especially during memory-guided saccades.

scholarly journals Lesions of mediodorsal thalamic nucleus reverse abnormal firing of the medial prefrontal cortex neurons in parkinsonian rats

2019 ◽  
Vol 14 (9) ◽  
pp. 1635 ◽  
Author(s):  
Ling-Ling Fan ◽  
Bo Deng ◽  
Jun-Bao Yan ◽  
Zhi-Hong Hu ◽  
Ai-Hong Ren ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Medial Prefrontal Cortex ◽  
Thalamic Nucleus ◽  
Mediodorsal Thalamic Nucleus

scholarly journals Clozapine Normalizes a Glutamatergic Transmission Abnormality Induced by an Impaired NMDA Receptor in the Thalamocortical Pathway via the Activation of a Group III Metabotropic Glutamate Receptor

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 234 ◽  
Author(s):  
Kouji Fukuyama ◽  
Ryo Kato ◽  
Masahiko Murata ◽  
Takashi Shiroyama ◽  
Motohiro Okada
Keyword(s):  
Glutamate Receptor ◽  
Thalamic Nucleus ◽  
Metabotropic Glutamate Receptor ◽  
Glutamate Release ◽  
Local Administration ◽  
Group Iii ◽  
Metabotropic Glutamate ◽  
Cultured Astrocytes ◽  
Nmda Glutamate Receptors ◽  
Toxic Concentrations

Pharmacological mechanisms of gold-standard antipsychotics against treatment-refractory schizophrenia, such as clozapine (CLZ), remain unclear. We aimed to explore the mechanisms of CLZ by investigating the effects of MK801 and CLZ on tripartite synaptic transmission in the thalamocortical glutamatergic pathway using multi-probe microdialysis and primary cultured astrocytes. l-glutamate release in the medial prefrontal cortex (mPFC) was unaffected by local MK801 administration into mPFC but was enhanced in the mediodorsal thalamic nucleus (MDTN) and reticular thalamic nucleus (RTN) via GABAergic disinhibition in the RTN–MDTN pathway. The local administration of therapeutically relevant concentrations of CLZ into mPFC and MDTN increased and did not affect mPFC l-glutamate release. The local administration of the therapeutically relevant concentration of CLZ into mPFC reduced MK801-induced mPFC l-glutamate release via presynaptic group III metabotropic glutamate receptor (III-mGluR) activation. However, toxic concentrations of CLZ activated l-glutamate release associated with hemichannels. This study demonstrated that RTN is a candidate generator region in which impaired N-methyl-d-aspartate (NMDA)/glutamate receptors likely produce thalamocortical hyperglutamatergic transmission. Additionally, we identified several mechanisms of CLZ relating to its superiority in treatment-resistant schizophrenia and its severe adverse effects: (1) the prevention of thalamocortical hyperglutamatergic transmission via activation of mPFC presynaptic III-mGluR and (2) activation of astroglial l-glutamate release associated with hemichannels. These actions may contribute to the unique clinical profile of CLZ.

scholarly journals Upregulated and Hyperactivated Thalamic Connexin 43 Plays Important Roles in Pathomechanisms of Cognitive Impairment and Seizure of Autosomal Dominant Sleep-Related Hypermotor Epilepsy with S284L-Mutant α4 Subunit of Nicotinic ACh Receptor

2020 ◽  
Vol 13 (5) ◽  
pp. 99 ◽  
Author(s):  
Kouji Fukuyama ◽  
Masashi Fukuzawa ◽  
Motohiro Okada
Keyword(s):  
Connexin 43 ◽  
Cognitive Deficit ◽  
Autosomal Dominant ◽  
Thalamic Nucleus ◽  
Glutamate Release ◽  
Glutamatergic Transmission ◽  
Transgenic Rats ◽  
Cx43 Expression ◽  
Mediodorsal Thalamic Nucleus ◽  
Thalamocortical Pathway

To understand the pathomechanism and pathophysiology of autosomal dominant sleep-related hypermotor epilepsy (ADSHE), we studied functional abnormalities of glutamatergic transmission in thalamocortical pathway from reticular thalamic nucleus (RTN), mediodorsal thalamic nucleus (MDTN) to orbitofrontal cortex (OFC) associated with S286L-mutant α4β2-nicotinic acetylcholine receptor (nAChR), and connexin43 (Cx43) hemichannel of transgenic rats bearing rat S286L-mutant Chrna4 gene (S286L-TG), corresponding to the human S284L-mutant CHRNA4 gene using simple Western analysis and multiprobe microdialysis. Cx43 expression in the thalamic plasma membrane fraction of S286L-TG was upregulated compared with that of wild-type. Subchronic administrations of therapeutic-relevant doses of zonisamide (ZNS) and carbamazepine (CBZ) decreased and did not affect Cx43 expression of S286L-TG, respectively. Upregulated Cx43 enhanced glutamatergic transmission during both resting and hyperexcitable stages in S286L-TG. Furthermore, activation of GABAergic transmission RTN–MDTN pathway conversely enhanced, but not inhibited, l-glutamate release in the MDTN via upregulated/activated Cx43. Local administration of therapeutic-relevant concentration of ZNS and CBZ acutely supressed and did not affect glutamatergic transmission in the thalamocortical pathway, respectively. These results suggest that pathomechanisms of ADSHE seizure and its cognitive deficit comorbidity, as well as pathophysiology of CBZ-resistant/ZNS-sensitive ADSHE seizures of patients with S284L-mutation.

scholarly journals Hippocampal CA1 pyramidal cells do not receive monosynaptic input from thalamic nucleus reuniens

2021 ◽  
Author(s):  
Lilya Andrianova ◽  
Erica S Brady ◽  
Gabriella Margetts-Smith ◽  
Shivali Kohli ◽  
Chris J McBain ◽  
...  
Keyword(s):  
Prefrontal Cortex ◽  
Thalamic Nucleus ◽  
Critical Role ◽  
Pyramidal Cells ◽  
Brain Regions ◽  
Thalamic Nuclei ◽  
Nucleus Reuniens ◽  
Ca1 Pyramidal Cells ◽  
Local Inhibition ◽  
The Many

Midline thalamic nuclei play a critical role in cognitive functions such as memory, decision-making and spatial navigation, by facilitating communication between the many brain regions involved in these processes. One canonical feature of thalamic interactions with the cortex or hippocampus appears to be that the thalamus receives input from, and projects to, excitatory neurons. Thalamic nucleus reuniens (NRe) is located on the midline and is viewed primarily as a relay from prefrontal cortex to hippocampal and entorhinal areas, although these connections are poorly defined at the cellular and synaptic level. Using electrophysiology and monosynaptic circuit-tracing, we found that pyramidal cells in CA1 receive no direct input from NRe. This contrasts starkly with prefrontal cortex, subiculum and entorhinal cortex, and indicates that NRe inputs to CA1 primarily drive local inhibition and not excitation they do in the other regions. The NRe to CA1 projection is thus a unique thalamic projection and as such is raising important questions about the function of NRe-mediated prefrontal control of the hippocampus.

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