The thalamus as a relay station and gatekeeper: relevance to brain disorders

Moustafa, Ahmed A.; McMullan, Ryan; Rostron, Bjorn; Hewedi, Doaa H.; Haladjian, Harry Haroutioun

doi:10.1515/revneuro-2016-0067

Cited by 49 publications

(37 citation statements)

References 127 publications

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“…The IC is part of the auditory pathway; it is interesting that hearing impairment is a frequently reported lingering effect of H 2 S intoxication in humans . The thalamus is a key brain region that is at the intersection of key neural tracts . Neurodegeneration in this region can virtually manifest in many of the clinical signs reported in human victims of H 2 S poisoning, including migraines .…”

Section: Discussionmentioning

confidence: 99%

“…50 The thalamus is a key brain region that is at the intersection of key neural tracts. 54 Neurodegeneration in this region can virtually manifest in many of the clinical signs reported in human victims of H 2 S poisoning, including migraines. 55 It will be of interest to determine why other regions are not vulnerable to the same extent as the IC and thalamus.…”

Section: Discussionmentioning

confidence: 99%

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Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae

Anantharam

Whitley²,

Mahama

et al. 2017

Annals of the New York Academy of Sciences

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Hydrogen sulfide (H S) is a highly neurotoxic gas. It is the second most common cause of gas-induced deaths. Beyond mortality, surviving victims of acute exposure may suffer long-term neurological sequelae. There is a need to develop countermeasures against H S poisoning. However, no translational animal model of H S-induced neurological sequelae exists. Here, we describe a novel mouse model of H S-induced neurotoxicity for translational research. In paradigm I, C57/BL6 mice were exposed to 765 ppm H S for 40 min on day 1, followed by 15-min daily exposures for periods ranging from 1 to 6 days. In paradigm II, mice were exposed once to 1000 ppm H S for 60 minutes. Mice were assessed for behavioral, neurochemical, biochemical, and histopathological changes. H S intoxication caused seizures, dyspnea, respiratory depression, knockdowns, and death. H S-exposed mice showed significant impairment in locomotor and coordinated motor movement activity compared with controls. Histopathology revealed neurodegenerative lesions in the collicular, thalamic, and cortical brain regions. H S significantly increased dopamine and serotonin concentration in several brain regions and caused time-dependent decreases in GABA and glutamate concentrations. Furthermore, H S significantly suppressed cytochrome c oxidase activity and caused significant loss in body weight. Overall, male mice were more sensitive than females. This novel translational mouse model of H S-induced neurotoxicity is reliable, reproducible, and recapitulates acute H S poisoning in humans.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae

Anantharam

Whitley²,

Mahama

et al. 2017

Annals of the New York Academy of Sciences

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“…Despite the paucity of data on thalamic microcircuit structural organization beyond these select sensory pathways, the notion that the thalamus is largely a relay station permeates the literature on thalamocortical interactions ( Mitchell, 2015 ; Moustafa et al, 2017 ; Sherman, 2017 ). For example, neurons in areas like the posterior Pulvinar nuclear complex or the Mediodorsal nucleus, which constitutes a large part of the human thalamus ( Chalfin et al, 2007 ) have been hypothesized to operate as higher order relays , transmitting signals from one cortical area to another.…”

Section: Introductionmentioning

confidence: 99%

Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

Mukherjee

Bajwa

Lam

et al. 2020

eLife

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The thalamus engages in sensation, action, and cognition, but the structure underlying these functions is poorly understood. Thalamic innervation of associative cortex targets several interneuron types, modulating dynamics and influencing plasticity. Is this structure-function relationship distinct from that of sensory thalamocortical systems? Here, we systematically compared function and structure across a sensory and an associative thalamocortical loop in the mouse. Enhancing excitability of mediodorsal thalamus, an associative structure, resulted in prefrontal activity dominated by inhibition. Equivalent enhancement of medial geniculate excitability robustly drove auditory cortical excitation. Structurally, geniculate axons innervated excitatory cortical targets in a preferential manner and with larger synaptic terminals, providing a putative explanation for functional divergence. The two thalamic circuits also had distinct input patterns, with mediodorsal thalamus receiving innervation from a diverse set of cortical areas. Altogether, our findings contribute to the emerging view of functional diversity across thalamic microcircuits and its structural basis.

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“…The functional profile of the thalamus goes far beyond the classical sphere of the central sensory pathways control. This complex brain structure affects almost all aspects of higher mental processes [93,94]. Several thalamic disturbances are also present in the course of schizophrenia [95,96,97,98,99].…”

Section: Expression Of Nmda Receptor Subunits In the Rat Brain Aftmentioning

confidence: 99%

NMDA Receptor Model of Antipsychotic Drug-Induced Hypofrontality

Krzystanek¹,

Pałasz²

2019

IJMS

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Schizophrenia is a chronic mental disease, affecting around 1% of the general population. Schizophrenia is characterized by productive, negative, affective, and disorganization symptoms, and cognitive deficits. Cognitive deficits prevail in most of the schizophrenia patients and are one of the most disabling symptoms. They usually occur before the acute episode of the disease and tend to become chronic with no satisfactory treatment from antipsychotic drugs. Because of their early manifestation in patients’ lives, cognitive deficits are suggested to be the primary symptom of schizophrenia. The pathogenesis of cognitive deficits in schizophrenia is not fully understood. They are linked with hypofrontality, which is a decrease in blood flow and glucose metabolism in the prefrontal lobe of schizophrenia-suffering patients. Hypofrontality is linked with disturbances of the corticolimbothalamic circuit, important for cognition and memory in humans. The circuit consists of a group of neuroanatomic structures and hypothetically any disturbance in them may result in cognitive deficits. We present a translational preclinical model of understanding how antipsychotic medication may decrease the N-methyl-D-aspartic acid (NMDA) receptors’ activity and produce dysfunctions in the corticolimbothalamic circuit and hypofrontality. From several pharmacological experiments on rats, including mainly our own recent findings, we collected data that suggest that antipsychotic medication may maintain and escalate hypofrontality in schizophrenia, decreasing NMDA receptor activity in the corticolimbothalamic circuit in the human brain. We discuss our findings within the literature of the subject.

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The thalamus as a relay station and gatekeeper: relevance to brain disorders

Cited by 49 publications

References 127 publications

Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae

Characterizing a mouse model for evaluation of countermeasures against hydrogen sulfide–induced neurotoxicity and neurological sequelae

Variation of connectivity across exemplar sensory and associative thalamocortical loops in the mouse

NMDA Receptor Model of Antipsychotic Drug-Induced Hypofrontality

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