Involvement of the thalamic reticular nucleus in prepulse inhibition of acoustic startle

You, Qiang-Long; Luo, Zhaoming; Luo, Zhiyong; Kong, Ying; Li, Zelin; Yang, Jian‐Ming; Li, Xiaowen; Gao, Tianming

doi:10.1038/s41398-021-01363-1

Cited by 6 publications

(3 citation statements)

References 49 publications

(37 reference statements)

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“…Therefore, it occupies a key position to modulate thalamo-cortical information flow [ 6 ]. The TRN is involved in regulation of sleep-arousal states [ 7 , 8 ], sleep spindles [ 9 ] and sleep-mediated memory consolidation [ 10 ], sensory filtering and discrimination [ 11 , 12 ], sensory gating [ 13 ], reversal learning requiring the switch from one sensory modality to another [ 14 ], modulation of fear extinction [ 15 ], flight behavior [ 16 ], and search strategies during spatial navigation [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Developmental oxidative stress leads to T-type Ca2+ channel hypofunction in thalamic reticular nucleus of mouse models pertinent to schizophrenia

et al. 2022

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Impairment of parvalbumin interneurons induced by oxidative stress (OxS) is a “hub” on which converge several genetic and environmental risk factors associated with schizophrenia. In patients, this could be a mechanism leading to anomalies of the thalamic reticular nucleus (TRN) whose major neuronal population expresses parvalbumin. The TRN shapes the information flow within thalamo-cortical circuits. The low-threshold voltage-gated T-type Ca2+ (T-Ca2+) channels (CaV3.2, CaV3.3) contribute to the excitability and rhythmic bursting of TRN neurons which mediates cortical sleep spindles, known to be affected in schizophrenia. Here, we investigated the impact of OxS during postnatal development and adulthood on firing properties and T-Ca2+ channels of TRN neurons. In Gclm knock-out (KO) mice, which display GSH deficit and OxS in TRN, we found a reduction of T-Ca2+ current density in adulthood, but not at peripuberty. In KO adults, the decreased T-Ca2+ currents were accompanied with a decrease of CaV3.3 expression, and a shift towards more hyperpolarized membrane potentials for burst firing leading to less prominent bursting profile. In young KO mice, an early-life oxidative challenge precipitated the hypofunction of T-Ca2+ channels. This was prevented by a treatment with N-acetylcysteine. The concomitant presence of OxS and hypofunction of T-Ca2+ channels were also observed in TRN of a neurodevelopmental model relevant to psychosis (MAM mice). Collectively, these data indicate that OxS-mediated T-Ca2+ hypofunction in TRN begins early in life. This also points to T-Ca2+ channels as one target of antioxidant-based treatments aiming to mitigate abnormal thalamo-cortical communication and pathogenesis of schizophrenia.

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Section: Introductionmentioning

confidence: 99%

Developmental oxidative stress leads to T-type Ca2+ channel hypofunction in thalamic reticular nucleus of mouse models pertinent to schizophrenia

et al. 2022

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“…These brain regions are associated with diverse behaviors. For example, hippocampal areas are implicated in spatial memory, fear memory, and social motivation [ 35 , 36 ]; the medial habenula and anterior amygdala are involved in fear/anxiety and sociability [ 33 , 34 ], the cortex is associated with multiple aspects of information processing [ 44 – 46 ], while the thalamus is involved in the startle reflex and sensorimotor gating [ 47 , 48 ]. Impairments in many of these brain regions can result in behavioral changes associated with disease.…”

Section: Discussionmentioning

confidence: 99%

Loss of GDE2 leads to complex behavioral changes including memory impairment

Daudelin,

Westerhaus,

Zhang

et al. 2024

Behav Brain Funct

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Background Alzheimer’s disease (AD) and amyotrophic lateral sclerosis/frontotemporal dementia (ALS/FTD) are debilitating neurodegenerative diseases for which there are currently no cures. Familial cases with known genetic causes make up less than 10% of these diseases, and little is known about the underlying mechanisms that contribute to sporadic disease. Accordingly, it is important to expand investigations into possible pathways that may contribute to disease pathophysiology. Glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) is a membrane-bound enzyme that acts at the cell surface to cleave the glycosylphosphatidylinositol (GPI)-anchor that tethers distinct proteins to the membrane. GDE2 abnormally accumulates in intracellular compartments in the brain of patients with AD, ALS, and ALS/FTD, indicative of GDE2 dysfunction. Mice lacking GDE2 (Gde2KO) show neurodegenerative changes such as neuronal loss, reduced synaptic proteins and synapse loss, and increased Aβ deposition, raising the possibility that GDE2 disruption in disease might contribute to disease pathophysiology. However, the effect of GDE2 loss on behavioral function and learning/memory has not been characterized. Results Here, we show that GDE2 is expressed throughout the adult mouse brain in areas including the cortex, hippocampus, habenula, thalamus, and amygdala. Gde2KO and WT mice were tested in a set of behavioral tasks between 7 and 16 months of age. Compared to WT, Gde2KO mice display moderate hyperactivity that becomes more pronounced with age across a variety of behavioral tests assessing novelty-induced exploratory activity. Additionally, Gde2KO mice show reduced startle response, with females showing additional defects in prepulse inhibition. No changes in anxiety-associated behaviors were found, but Gde2KOs show reduced sociability. Notably, aged Gde2KO mice demonstrate impaired short/long-term spatial memory and cued fear memory/secondary contextual fear acquisition. Conclusions Taken together, these observations suggest that loss of GDE2 leads to behavioral deficits, some of which are seen in neurodegenerative disease models, implying that loss of GDE2 may be an important contributor to phenotypes associated with neurodegeneration.

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“…This organizational scheme was first characterized in sensory processing but applies to other functional modalities (22). Given its complex interconnections, TRN deficits can cause network-level dysfunctions and behavioral abnormalities relevant to neurodevelopmental disorders (23), including schizophrenia (24)(25)(26). Indeed, 19 risk genes are robustly expressed in the TRN of schizophrenia patients (27).…”

Section: Introductionmentioning

confidence: 99%

Thalamic reticular nucleus impairments and abnormal prefrontal control of dopamine system in a developmental model of schizophrenia: prevention by N-acetylcysteine

et al. 2021

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Recent evidence showed thalamic abnormalities in schizophrenia involving disruptions to the parvalbumin neurons in the thalamic reticular nucleus (TRN). However, their functional consequences, as well as a potential linkage to oxidative stress, are unclear. The TRN is posited to gate prefrontal control of dopamine neuron activity in the ventral tegmental area (VTA). Thus, we hypothesized that schizophrenia-related TRN abnormalities might contribute to dopamine dysregulation, a well-known feature of the disorder. To test this, in adult rats exposed prenatally to methylazoxymethanol acetate (MAM rats), oxidative impairments to the parvalbumin neurons in the anterior TRN were assessed by immunohistochemistry. Using in vivo electrophysiology, we investigated whether inactivation of the prefrontal cortex would produce differential effects on VTA dopamine neurons in MAM rats. We show that MAM rats displayed reduced markers of parvalbumin and wisteria floribunda agglutinin-labeled perineuronal nets, correlating with increased markers of oxidative stress (8-oxo-7, 8-dihydro-20-deoxyguanosine and 3-Nitrotyrosine). Moreover, MAM rats displayed heightened baseline and abnormal prefrontal control of VTA dopamine neuron activity, as tetrodotoxin-induced inactivation of the infralimbic prefrontal cortex decreased the dopamine population activity, contrary to the normal increase in controls. Such dopamine neuron dysregulation was recapitulated by enzymatic perineuronal net digestion in the TRN of normal rats. Furthermore, juvenile (postnatal day 11-25) antioxidant treatment (N-acetyl-cysteine; 900mg/L; drinking water) prevented all these impairments in MAM Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

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Involvement of the thalamic reticular nucleus in prepulse inhibition of acoustic startle

Cited by 6 publications

References 49 publications

Developmental oxidative stress leads to T-type Ca2+ channel hypofunction in thalamic reticular nucleus of mouse models pertinent to schizophrenia

Developmental oxidative stress leads to T-type Ca2+ channel hypofunction in thalamic reticular nucleus of mouse models pertinent to schizophrenia

Loss of GDE2 leads to complex behavioral changes including memory impairment

Thalamic reticular nucleus impairments and abnormal prefrontal control of dopamine system in a developmental model of schizophrenia: prevention by N-acetylcysteine

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