Neuroscience Research最新文献

Somatosensory deficits from stroke, spinal cord injury, or other neurologic damage can lead to a significant degree of functional impairment. The primary (SI) and secondary (SII) somatosensory cortices encode information in a medial to lateral organization. SI is generally organized topographically, with more discrete cortical representations of specific body regions. SII regions corresponding to anatomical areas are less discrete and may represent a more functional rather than topographic organization. Human somatosensory research continues to map cortical areas of sensory processing with efforts primarily focused on hand and upper extremity information in SI. However, research into SII and other body regions is lacking. In this review, we synthesize the current state of knowledge regarding the cortical organization of human somatosensation and discuss potential applications for brain computer interface. In addition to accurate individualized mapping of cortical somatosensation, further research is required to uncover the neurophysiological mechanisms of how somatosensory information is encoded in the cortex.

Altered cholesterol metabolism is implicated in brain ageing and Alzheimer’s disease. We examined whether key genes regulating cholesterol metabolism and levels of brain cholesterol are altered in dementia and Alzheimer’s disease neuropathological change (ADNC). Temporal cortex (n = 99) was obtained from the Cognitive Function and Ageing Study. Expression of the cholesterol biosynthesis rate-limiting enzyme HMG-CoA reductase (HMGCR) and its regulator, SREBP2, were detected using immunohistochemistry. Expression of HMGCR, SREBP2, CYP46A1 and ABCA1 were quantified by qPCR in samples enriched for astrocyte and neuronal RNA following laser-capture microdissection. Total cortical cholesterol was measured using the Amplex Red assay. HMGCR and SREBP2 proteins were predominantly expressed in pyramidal neurones, and in glia. Neuronal HMGCR did not vary with ADNC, oxidative stress, neuroinflammation or dementia status. Expression of HMGCR neuronal mRNA decreased with ADNC (p = 0.022) and increased with neuronal DNA damage (p = 0.049), whilst SREBP2 increased with ADNC (p = 0.005). High or moderate tertiles for cholesterol levels were associated with increased dementia risk (OR 1.44, 1.58). APOE ε4 allele was not associated with cortical cholesterol levels. ADNC is associated with gene expression changes that may impair cholesterol biosynthesis in neurones but not astrocytes, whilst levels of cortical cholesterol show a weak relationship to dementia status.

Second language learners and educators often believe that improving one’s listening ability hinges on acquiring an extensive vocabulary and engaging in thorough listening practice. Our previous study suggested that listening comprehension is also impacted by the ability to produce vocabulary. Nevertheless, it remained uncertain whether quick comprehension could be attributed to a simple acceleration of processing or to changes in neural activity. To identify neural activity changes during sentence listening comprehension according to different levels of lexical knowledge (productive, only comprehensive, uncomprehensive), we measured participants’ electrical activity in the brain via electroencephalography (EEG) and conducted a time-frequency-based EEG power analysis. Additionally, we employed a decoding model to verify the predictability of vocabulary knowledge levels based on neural activity. The decoding results showed that EEG activity could discriminate between listening to sentences containing phrases that include productive knowledge and ones without. The positive impact of productive vocabulary knowledge on sentence comprehension, driven by distinctive neural processing during sentence comprehension, was unequivocally evident. Our study emphasizes the importance of productive vocabulary knowledge acquisition to enhance the process of second language listening comprehension.

Neocortical slow waves are critical for memory consolidation. The retrosplenial cortex is thought to facilitate the slow wave propagation to regions beyond the neocortex. However, it remains unclear which population is responsible for the slow wave propagation. To address this issue, we performed in vivo whole-cell recordings to identify neurons that were synchronous and asynchronous with slow waves. By quantifying their intrinsic membrane properties, we observed that the former exhibited regular spiking, whereas the latter exhibited late spiking. Thus, these two cell types transmit information in different directions between the neocortex and subcortical regions.

Repeated cold stress (RCS) can trigger the development of fibromyalgia (FM)-like symptoms, including persistent deep-tissue pain, although nociceptive changes to the skin have not been fully characterized. Using a rat RCS model, we investigated nociceptive behaviors induced by noxious mechanical, thermal, and chemical stimuli applied to plantar skin. Neuronal activation in the spinal dorsal horn was examined using the formalin pain test. In rats exposed to RCS, nociceptive behavioral hypersensitivity was observed in all modalities of cutaneous noxious stimuli: the mechanical withdrawal threshold was decreased, and the heat withdrawal latency was shortened one day after the cessation of stress. The duration of nocifensive behaviors in the formalin test was prolonged in phase II but not in phase I. The number of c-Fos-positive neurons increased in the entire dorsal horn laminae I-VI, ipsilateral, but not contralateral, to formalin injection at the L3-L5 segments. The duration of nocifensive behavior in phase II was significantly and positively correlated with the number of c-Fos-positive neurons in laminae I-II. These results demonstrate that cutaneous nociception is facilitated in rats exposed to RCS for a short time and that the spinal dorsal horn neurons are hyperactivated by cutaneous formalin in the RCS model.

In the present study, we attempted to temporally and quantitatively analyze the functional contributions of Ca²⁺-permeable (CP) α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) during long-term potentiation (LTP) expression using electrophysiological and pharmacological approaches. In hippocampal CA1 neurons, using 1-naphthyl acetyl spermine (NASPM), a CP-AMPAR antagonist, we began by demonstrating that NASPM-sensitive components, probably including the GluA1 homomer, functionally contributed to about 15% of AMPAR-mediated EPSC amplitude in basal conditions. Then, when NASPM was treated at different time points (3–30 min) after LTP induction, it was found that LTP was almost completely impaired at 3 or 10 min but maintained at 20 or 30 min, although its potentiation was reduced. Further temporal and quantitative analysis revealed that the functional expression of CP-AMPARs began increasing approximately 20 min after LTP induction and reached more than twice the basal level at 30 min. These results suggest that CP-AMPARs in the first 3–10 min of LTP might play an important role in LTP maintenance. Moreover, their decay time was also significantly increased at 30 min, suggesting that CP-AMPARs changed not only quantitatively in LTP but also qualitatively.

Neurodevelopment is highly affected by perinatal ethanol exposure (PEE). In the adult brain, neurogenesis takes place in the dentate gyrus (DG) of the hippocampus and in the subventricular zone. This work aimed to analyze the effect of PEE on the cellular types involved in adult dorsal hippocampal neurogenesis phases using a murine model. For this purpose, primiparous female CD1 mice consumed only ethanol 6% v/v from 20 days prior to mating and along pregnancy and lactation to ensure that the pups were exposed to ethanol throughout pre- and early postnatal development. After weaning, pups had no further contact with ethanol. Cell types of the adult male dorsal DG were studied by immunofluorescence. A lower percentage of type 1 cells and immature neurons and a higher percentage of type 2 cells were observed in PEE animals. This decrease in type 1 cells suggests that PEE reduces the population of remnant progenitors of the dorsal DG present in adulthood. The increase in type 2 cells and the decrease in immature neurons indicate that, during neurodevelopment, ethanol alters the capacity of neuroblasts to become neurons in the adult neurogenic niche. These results suggest that pathways implicated in cell determination are affected by PEE and remain affected in adulthood.

How do neurons encode the information that underlies cognition, internal states, and behavior? This review focuses on the neural circuit mechanisms underlying sleep in Drosophila and, to illustrate the power of addressing neural coding in this system, highlights a specific circuit mediating the circadian regulation of sleep quality. This circuit exhibits circadian cycling of sleep quality, which depends solely on the pattern (not the rate) of spiking. During the night, the stability of spike waveforms enhances the reliability of spike timing in these neurons to promote sleep quality. During the day, instability of the spike waveforms leads to uncertainty of spike timing, which remarkably produces synaptic plasticity to induce arousal. Investigation of the molecular and biophysical basis of these changes was greatly facilitated by its study in Drosophila, revealing direct connections between genes, molecules, spike biophysical properties, neural codes, synaptic plasticity, and behavior. Furthermore, because these patterns of neural activity change with aging, this model system holds promise for understanding the interplay between the circadian clock, aging, and sleep quality. It is proposed here that neurophysiological investigations of the Drosophila brain present an exceptional opportunity to tackle some of the most challenging questions related to neural coding.

Structural and functional recovery from stress-induced depression is impaired in the context of aging brain. Since investigating the molecular substrates that facilitate behavioral recovery may have important implications for understanding brain plasticity and resilience of individuals, we studied depressive-like behaviors in young and aged rats 6 weeks after chronic stress exposure as a recovery period and examined the levels of TNF-α and IL-6 inflammatory cytokines, NADH oxidase activity, NADPH oxidase, endoplasmic reticulum (ER) stress markers, and apoptosis in the hippocampus. Young (3 months old) and aged (22 months old) male Wistar rats were divided into four groups; young control (Young), depression model of young rats that received chronic stress procedure followed by a 6-week recovery period (Young+S), aged control (Aged), and depression model of aged rats that received chronic stress procedure followed by a 6-week recovery period (Aged+S). After the recovery period, aged but not young rats showed depression-like behaviors, evaluated by the sucrose preference test (SPT) and forced swimming test (FST), coincided with the altered levels of TNF-α, IL-6, NADH oxidase activity, NADPH oxidase, GRP78, CHOP, and cleaved caspase-12 in the hippocampus of these animals. These data suggested that oxidative and ER stress-induced apoptosis in the aging hippocampus may affect the recovery-related outcomes after the stress paradigm.

Brain health is largely dependent on the metabolic regulation of amino acids. Brain injuries, diseases, and disorders can be detected through alterations in free amino acid (FAA) concentrations; and thus, mapping the changes has high diagnostic potential. Common methods focus on optimizing neurotransmitter quantification; however, recent focus has expanded to investigate the roles of molecular precursors in brain metabolism. An isocratic method using high performance liquid chromatography with electrochemical cell detection was developed to quantify a wide range of molecular precursors and neurotransmitters: alanine, arginine, aspartate, serine, taurine, threonine, tyrosine, glycine, glutamate, glutamine, and γ-Aminobutyric acid (GABA) following traumatic brain injury. First, baseline concentrations were determined in the serum, cerebrospinal fluid, hippocampus, cortex, and cerebellum of naïve male Sprague Dawley rats. A subsequent study was performed investigating acute changes in FAA concentrations following blast-induced traumatic brain injury (bTBI). Molecular precursor associated FAAs decreased in concentration at 4 h after injury in both the cortex and hippocampus while those serving as neurotransmitters remained unchanged. In particular, the influence of oxidative stress on the observed changes within alanine and arginine pathways following bTBI should be further investigated to elucidate the full therapeutic potential of these molecular precursors at acute time points.