Sensorimotor gating in NTS1 and NTS2 null mice: effects of <i>d</i>-amphetamine, dizocilpine, clozapine and NT69L

Oliveros, Alfredo; Heckman, Michael G.; CORENA-Mcleod, María; Williams, Katrina; Boules, Mona; Richelson, Elliott

doi:10.1242/jeb.046318

Cited by 12 publications

(5 citation statements)

References 56 publications

(91 reference statements)

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“…Mice were allowed to acclimate for 1h in the PPI experimental room on test day. Following this acclimation period, mice were subjected to the PPI experimental protocol as previously described (Oliveros et al, 2010). Each animal was individually placed within a Plexiglas cylinder (12.7 cm long×1.5 cm in diameter) resting on a Plexiglas frame (12.7 cm×20.3 cm) housed within the startle response chamber (38.1 cm×40.6 cm×58.4 cm, San Diego Instruments, San Diego, CA, USA).…”

Section: Startle and Ppi Paradigmmentioning

confidence: 99%

Neurogranin regulates sensorimotor gating through cortico-striatal circuitry

et al. 2019

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Glutamate dysregulation is known to contribute to many psychiatric disorders including schizophrenia. Aberrant cortico-striatal activity and therefore glutamate levels might be relevant to this disease characterized by reduced prepulse inhibition (PPI), however, the molecular and behavioral mechanism of the pathophysiology of schizophrenia remains unclear. The focus of this study was to contribute to the current understanding of the glutamate and neurogranin (Ng) pathway, in relation to the cortico-striatal pathology of schizophrenia using a mouse model. A variant of the Ng gene has been detected in people with schizophrenia, implicating maladaptation of cortical glutamate signaling and sensorimotor gating. To test Ng-mediated PPI regulation in the mouse model, we utilized Ng null mice, viral-mediated Ng expression, and genetics approaches. Our results demonstrate that lack of Ng in mice decreases PPI. Ng over-expression in the prefrontal cortex (PFC) increases PPI, while Ng expression in either the nucleus accumbens (NAc) or hippocampus induces no change in PPI. Using optogenetics and chemogenetics, we identified that cortico-striatal activation is involved in PPI regulation. Finally, pharmacological regulation of Ng using glutamate receptor inhibitors demonstrated altered PPI between genotypes. In this study, we have investigated the impact of Ng expression on sensorimotor gating. This study contributes to a better understanding of the glutamatergic theory of schizophrenia, opening novel therapeutic avenues that may lead to glutamatergic treatments to ameliorate the symptoms of schizophrenia.

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Section: Startle and Ppi Paradigmmentioning

confidence: 99%

Neurogranin regulates sensorimotor gating through cortico-striatal circuitry

et al. 2019

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“…Given that previous studies have shown deficits in conditioned stimulus (CS+) learning during LPS treatment, 26 we questioned whether 2×-LPS administration would attenuate the acquisition of stimulus-reward learning during Pavlovian conditioning. 27,28 To control for the decreased weight of the 2×-LPS-treated mice, vehicle-treated mice were food restricted and weights were closely monitored daily during conditioning. To establish a tone-reward contingency during conditioning, mice were given a random series of CS+ tone cues (65 dB and 0.25 seconds duration; ENV-323HAM, 4500 Hz Sonalert, Med-Associates), paired with delivery of a 10 µL sucrose reward.…”

Section: Behavior Testingmentioning

confidence: 99%

“…Prepulse inhibition testing was conducted as previously described. 24,28 PPI was measured in sound-attenuating boxes (SR-Lab, San Diego Instruments, San Diego CA, USA) equipped with a loudspeaker and house light. Each chamber accommodated a cylindrical plexiglass animal enclosure which rested on a platform containing a piezoelectric accelerometer mounted beneath.…”

Section: Behavior Testingmentioning

confidence: 99%

Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice

Peyton

Oliveros

Tufvesson-Alm

et al. 2019

Int J�Tryptophan�Res

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Kynurenic acid (KYNA), a glial-derived metabolite of tryptophan metabolism, is an antagonist of the alpha 7 nicotinic acetylcholine receptor and the glycine-binding site of N-methyl-d-aspartate (NMDA) receptors. Kynurenic acid levels are increased in both the brain and cerebrospinal fluid of several psychiatric disorders including bipolar disorder, schizophrenia, and Alzheimer disease. In addition, pro-inflammatory cytokines have been found to be elevated in the blood of schizophrenic patients suggesting inflammation may play a role in psychiatric illness. As both pro-inflammatory cytokines and KYNA can be elevated in the brain by peripheral lipopolysaccharide (LPS) injection, we therefore sought to characterize the role of neuroinflammation on learning and memory using a well-described dual-LPS injection model. Mice were injected with an initial injection (0.25 mg/kg LPS, 0.50 mg/kg, or saline) of LPS and then administrated a second injection 16 hours later. Our results indicate both 0.25 and 0.50 mg/kg dual-LPS treatment increased l-kynurenine and KYNA levels in the medial pre-frontal cortex (mPFC). Mice exhibited impaired acquisition of CS+ (conditioned stimulus) Pavlovian conditioning. Notably, mice showed impairment in reference memory while working memory was normal in an 8-arm maze. Taken together, our findings suggest that neuroinflammation induced by peripheral LPS administration contributes to cognitive dysfunction.

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“…All mice received the same dual injection protocol (Supplementary Fig.1A). PPI was tested as previously described (Oliveros et al, 2010). Briefly, PPI was measured in sound-attenuating cubicles (SR-LAB, San Diego Instruments, San Diego CA, USA) that were equipped with a house light and a loudspeaker.…”

Section: Methodsmentioning

confidence: 99%

LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning

Oliveros

Wininger

Larsson

et al. 2017

Journal of Neuroimmunology

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The N-Methyl-D-Aspartate receptor (NMDAR) antagonist kynurenic acid (KYNA) and the post-synaptic calmodulin binding protein neurogranin (Nrgn) have been implicated in neurological and neuropsychiatric conditions including Alzheimer's disease and schizophrenia. This study indicates that systemic dual-lipopolysaccharide (LPS) injections increases KYNA in the medial prefrontal cortex (mPFC), which is accompanied with increased phosphorylation of nuclear factor kappa chain of activated B cells (NFκB) and activation of the nuclear factor of activated T- cells (NFAT). Our results also indicate that dual-LPS increases Nrgn phosphorylation and concomitantly reduces phosphorylation of calmodulin kinase-I I (CaMKII). We confirmed that systemic blockade of kynurenine-3 monooxygenase in conjunction with kynurenine administration results in significant increases in Nrgn phosphorylation and a significant reduction of CaMKII phosphorylation in the mPFC. Consequently dual-LPS administration induced significant impairments in stimulus processing during Pavlovian conditioning. Taken together, our study indicates that elevations in KYNA in the mPFC can directly regulate NMDA-Nrgn-CaMKII signaling, suggesting that neuroinflammatory conditions affecting this pathway may be associated with cognitive dysfunction.

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Sensorimotor gating in NTS1 and NTS2 null mice: effects of d-amphetamine, dizocilpine, clozapine and NT69L

Cited by 12 publications

References 56 publications

Neurogranin regulates sensorimotor gating through cortico-striatal circuitry

Neurogranin regulates sensorimotor gating through cortico-striatal circuitry

Lipopolysaccharide Increases Cortical Kynurenic Acid and Deficits in Reference Memory in Mice

LPS-induced cortical kynurenic acid and neurogranin-NFAT signaling is associated with deficits in stimulus processing during Pavlovian conditioning

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