Neuroscience
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The contactin-associated protein-like 2 (CNTNAP2) gene encodes for the CASPR2 protein, which plays an essential role in neurodevelopment. Mutations in CNTNAP2 are associated with neurodevelopmental disorders, including autism spectrum disorder and schizophrenia. Rats with a loss of function mutation in the Cntnap2 gene show increased acoustic startle response (ASR) and decreased prepulse inhibition (PPI). ⋯ Female Cntnap2-/- rats showed considerably increased PnC firing rates compared with female wildtypes, whereas the difference between the genotypes was modest in male rats. In contrast, for both females and males we found meager differences between the genotypes for PPTg firing rates and inhibition of PnC firing rates, indicating that altered firing rates of these brainstem structures are not responsible for decreased PPI in Cntnap2-/- rats. We conclude that the auditory processing changes seen in Cntnap2-/- rats are associated with, but cannot be fully explained by, differences in PnC firing rates, and that a loss of function mutation in the Cntnap2 gene has differential effects depending on sex.
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Subjective cognitive decline (SCD) and objective subtle cognitive difficulties (Obj-SCD) are considered the initial stages of aberrant cognition prior to mild cognitive impairment (MCI) due to Alzheimer's disease (AD). We aimed to determine the difference of brain function of SCD and Obj-SCD, furthermore, to figure out which one could be the marker of early AD. One hundred and eighty-five participants were enrolled in this study to determine the amyloid pathology and glucose metabolism changes in SCD and Obj-SCD. ⋯ Amyloid deposition was associated with function of memory, language and executive domains, and glucose metabolism was only associated with executive function in Obj-SCD. Amyloid deposition was only associated with executive function in SCD. Obj-SCD could be the early stage of AD, which displayed significant increased amyloid deposition, and the increased amyloid deposition was associated with cognitive function in different domains.
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N-methyl-D-aspartate receptor (NMDAR) hypofunction during brain development is likely to contribute to the manifestation of schizophrenia (SCZ) in young adulthood. The cellular targets of NMDAR hypofunction appear to be at least in part corticolimbic fast-spiking (FS) interneurons. However, functional alterations in parvalbumin (PV)-positive FS interneurons following NMDAR hypofunction are poorly understood. ⋯ Treatment with the Cav2.1/2.2 channel agonist GV-58 augmented somatic Ca2+ currents and GABA release in Cacna1a-haploinsufficient PV interneurons, but failed to enhance GABA release in the Grin1-deleted PV interneurons. Taken together, our results suggest that Grin1 deletion in prospective PV interneurons impairs proper maturation of membrane excitability and Cav2.1-recruited evoked GABA release. This may increase synaptic excitatory/inhibitory ratio in principal neurons, contributing to the emergence of SCZ-like phenotypes.
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Some patients with a visual field loss due to a lesion in the primary visual cortex (V1) can shift their gaze to stimuli presented in their blind visual field. The extent to which a similar "blindsight" capacity is present in neurologically healthy individuals remains unknown. Using retinotopically navigated transcranial magnetic stimulation (TMS) of V1 (Experiment 1) and metacontrast masking (Experiment 2) to suppress conscious vision, we examined neurologically healthy humans' ability to make saccadic eye movements toward visual targets that they reported not seeing. ⋯ Signal detection theoretic measures suggested that in the TMS experiment, saccades toward unseen targets may have been based on weak conscious experiences. In both experiments, reduced visibility of the target stimulus was associated with slower and less precise gaze shifts. These results suggest that saccades made by neurologically healthy humans may be influenced by unconscious information, although the initiation of saccades is largely based on conscious vision.