Neuroscience Research最新文献

The primary motor cortex (M1) is believed to be a cortical center for the execution of limb movements. Although M1 neurons mainly project to the spinal cord on the contralateral side, some M1 neurons project to the ipsilateral side via the uncrossed corticospinal pathway. Moreover, some M1 neurons are activated during ipsilateral forelimb movements. However, the extent to which M1 neurons are involved in ipsilateral movement execution has not been determined. Therefore, we investigated the involvement of M1 neurons in the initiation of ipsilateral and contralateral hand movements by examining trial-by-trial correlations between premovement neuronal spikes and hand movement reaction times in monkeys. Overall, the activity of M1 neurons was more strongly correlated with the reaction times for contralateral hand movements than those for ipsilateral hand movements. However, the activity of some M1 neurons was correlated with reaction times for ipsilateral hand movements, and these correlations were as strong as those between the activity of other M1 neurons and reaction times for contralateral hand movements. This finding suggests that one subset of M1 neurons sends motor commands for ipsilateral hand movements to the same extent as another subset of M1 neurons sends motor commands for contralateral hand movements.

Sensorineural hearing loss causes cell death in central auditory neurons, but molecular mechanisms of triggering this process are not fully understood. We report here that loss of afferent activity promotes cell death by facilitating proBDNF-p75NTR signals in cochlear nucleus of chicks around hatch. RNA-seq analyses revealed up-regulation of genes related to proBDNF-p75NTR-JNK signals as well as apoptosis at the nucleus within 24hours after unilateral cochlea deprivation. Western blotting confirmed a high level of proBDNF protein at the nucleus. Moreover, FLAG-tagged p75NTR accumulated at the plasma membrane of the neurons within 6hours after the deprivation, well before the upregulation of apoptotic genes. Cell viability assay using propidium iodide in organ culture showed that proBDNF increased the fraction of dying neurons in a dose-dependent manner. In addition, pharmacological blockades of synaptic and spike activities in the culture reproduced the surface accumulation of p75NTR in vivo and increased the fraction of dying neurons, while genetic inhibition of p75NTR signals occluded the cell death during the activity blockades. These results indicate that afferent activity is crucial for suppressing surface accumulation of p75NTR and hence proBDNF-p75NTR signals and that the loss of this suppression would contribute to triggering cell death after deafferentation in the developing brainstem auditory circuit.

Huntingtin-associated protein 1 (HAP1) is an essential constituent of the stigmoid body (STB) and is known as a neuroprotective interactor with causal agents for several neurodegenerative disorders, including huntingtin (HTT) in Huntington's disease. Previous in vitro studies showed that compared to normal HTT, STB/HAP1 exhibited a higher binding affinity for mutant HTT. The detailed in vivo relationships of STB/HAP1 with endogenous HTT, however, have not been clarified yet. This study examined the distribution of endogenous HTT and its relationships with STB/HAP1 in the adult mouse brain and spinal cord using light/fluorescence microscopy. Our results show that HTT immunoreactivity is highly distributed in the striatum, medial septal nucleus (MS), nucleus of the horizontal limb/ vertical limb of the diagonal band of Broca (HDB, VDB), substantia innominata basal part (SIB), pedunculopontine tegmental nucleus (PPTg), laterodorsal tegmental nucleus (LDTg), autonomic preganglionic neurons, and brainstem/spinal motoneurons. More than 90 % of HTT-immunoreactive (ir) neurons contain STB/HAP1 immunoreactivity in MS, VBD/HDB, SIB, PPTg, LDTg, and autonomic preganglionic nuclei. HTT-ir neurons in the striatal and motor nuclei, however, do not exhibit HAP1 immunoreactivity. These suggest that due to the absence of STB/HAP1-protectivity, HTT-ir striatal/motor neurons are more vulnerable to neurodegeneration than other HAP1-expressing HTT neurons. Our current findings might provide a framework for elucidating the pathophysiological functions of endogenous HTT and HAP1 in the central nervous system.

In mammals, lactation is essential for the health and growth of infants and supports the formation of the mother-infant bond. Breastfeeding is mediated by the neurohormone oxytocin (OT), which is released into the bloodstream in a pulsatile manner from OT neurons in the hypothalamus to promote milk ejection into mammary ducts. While classical studies using anesthetized rats have illuminated the activity patterns of putative OT neurons during breastfeeding, the molecular, cellular, and neural circuit mechanisms driving the synchronous pulsatile bursts of OT neurons in response to nipple stimulation remain largely elusive. Only recently have molecular neuroscience techniques for imaging and manipulating specific genetically defined cells been applied to lactating mice. For instance, fiber photometry has revealed the temporal dynamics of the population pulsatile activity of OT neurons in freely moving dams across various lactation stages, while microendoscopy has provided single-cell level insights. In this review, we introduce the neuroscience of lactation with respect to OT neuron activity, discuss findings from molecular neuroscience approaches, and highlight key unresolved questions.

Pronouns create cohesive links in discourse by referring to previously mentioned elements. Here, we focus on pronominalization during speech production in three experiments employing ERP and fMRI methodologies. Participants were asked to produce two short sentences describing a man or woman using an object. In the second sentence, they were instructed to use a pronoun to refer to the same person and a noun to refer to a different person. The first ERP experiment revealed that noun conditions elicited more negative ERPs starting at 220 ms, with significant differences in early and later time windows, particularly in the left hemisphere. The second ERP experiment showed divergence at 280 ms, with significant differences between 300 and 400 ms at midline electrodes, again indicating more negative ERPs for nouns. The fMRI experiment identified greater activations for nouns than pronouns in regions like the superior temporal gyrus (STG) and cerebellar vermis, suggesting higher working memory load and lexical retrieval demands for nouns compared to pronouns. Moreover, pronouns elicited an enhanced centro-parietal positivity, indicating increased attentional demands. These findings suggest that while noun processing requires greater working memory and lexical retrieval, pronoun processing engages more attentional resources. This study advances our understanding of the neural mechanisms underlying pronominalization during speech production, highlighting distinct neural responses for nouns and pronouns.

Sleep bruxism is an involuntary, exaggerated jaw-closing activity during sleep. Selective serotonin reuptake inhibitor (SSRI) use is a risk factor for bruxism. However, the effect of various SSRIs on masseter (jaw-closing) muscle activity remains unclear. Here, we examined the effects of long-term administration of two SSRIs, fluoxetine (FLX) and paroxetine (PRX), for 14 days on masseter muscle activity during wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep for 24 h in mice. Vigilance states were scored based on electroencephalographic, electrooculography and neck electromyographic (EMG) activities. The EMG activity of the masseter muscle was quantified in 6 h periods. FLX and PRX did not affect the duration of the three vigilance states. Both drugs significantly prolonged the REM sleep episode duration while decreasing the number of episodes. FLX significantly increased REM sleep onset latency. Neither FLX nor PRX affected the mean masseter EMG activity during wakefulness. FLX significantly increased the relative time of masseter muscle activity in NREM sleep during 02:00-08:00 and 08:00-14:00, while PRX did not affect three vigilance states. Overall, FLX had a limited but significant effect on masseter muscle activity in NREM sleep during specific periods.

Astrocytes are the most abundant and morphologically complex glial cells that play active roles in the central nervous system (CNS). Recent research has identified shared and region-specific astrocytic genes and functions, elucidated the cellular origins of their regional diversity, and uncovered the molecular networks for astrocyte morphology, which are essential for their functional complexity. Reactive astrocytes exhibit a wide range of functional diversity in a context-specific manner in CNS disorders. This review discusses recent advances in understanding the molecular and morphological diversity of astrocytes in healthy individuals and those with neurodegenerative diseases, such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis.

The superior colliculus (SC) receives inputs from various brain regions in a layer- and radial subregion-specific manner, but whether the SC exhibits subregion-specific dynamics remains unclear. To address this issue, we recorded the spiking activity of single SC neurons while photoactivating cortical areas in awake head-fixed Thy1-ChR2 rats. We classified 309 neurons that responded significantly into 8 clusters according to the response dynamics. Among them, neurons with monophasic excitatory responses (7-12 ms latency) that returned to baseline within 20 ms were commonly observed in the optic and intermediate gray layers of centromedial and centrolateral SC. In contrast, neurons with complex polyphasic responses were commonly observed in the deep layers of the anterolateral SC. Cross-correlation analysis suggested that the complex pattern could be only partly explained by an internal circuit of the deep gray layer. Our results indicate that medial to centrolateral SC neurons simply relay cortical activity, whereas neurons in the deep layers of the anterolateral SC dynamically integrate inputs from the cortex, SNr, CN, and local circuits. These findings suggest a spatial gradient in SC integration, with a division of labor between simple relay circuits and those integrating complex dynamics.

Long-term depression (LTD) is a form of synaptic plasticity thought to be the cellular basis of experience-dependent learning and memory. LTD is caused by an activity-dependent decrease in cell surface α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPA receptors) at the postsynaptic sites. However, the mechanism through which AMPA receptors are removed from the cell surface via neuronal activity is not fully understood. In this study, we showed that small interfering RNA (siRNA)-mediated knockdown of sterile alpha and toll/interleukin receptor motif containing 1 (SARM1) in cultured hippocampal neurons prevented the N-methyl-d-aspartate (NMDA)-induced reduction in cell surface AMPA receptors. However, the control RNA did not affect NMDA-mediated AMPA receptor trafficking. Overexpression of the siRNA-resistant form of SARM1 in SARM1-knocked-down neurons restored AMPA receptor trafficking. However, overexpression of SARM1, which lacks the mitochondrial transport signal, in the SARM1-knocked-down neurons did not restore NMDA-dependent AMPA receptor endocytosis. Moreover, the inhibition of the NADase activity of SARM1 blocked the NMDA-induced reduction of cell surface AMPA receptors. These results suggest that both the mitochondrial localization and NADase activity of SARM1 are essential for NMDA receptor-dependent AMPA receptor internalization in the hippocampal neurons.

This review examines the complex interactions between estrogen receptors α and β (ERα and ERβ) and arginine vasopressin (AVP), delving into their significant roles in modulating empathy, a critical psychological component in human social dynamics. Empathy, integrating affective and cognitive elements, is anchored in neural regions like the amygdala and prefrontal cortex. ERα and ERβ, pivotal in estrogen regulation, influence neurotransmitter dynamics and neural network activities, crucial for empathic development. AVP, key in regulating water balance, blood pressure, and social behaviors, interplays with these receptors, profoundly impacting empathic responses. The study highlights that ERα predominantly enhances empathy, especially affective empathy, by stimulating AVP synthesis and release. In contrast, ERβ may diminish empathy in certain contexts by suppressing AVP expression and activity. The intricate interplay, homeostatic balance, and mutual conversion between ERα and ERβ in AVP regulation are identified as challenging yet crucial areas for future research. These findings provide essential insights into the neurobiological underpinnings of empathy, offering new avenues for therapeutic interventions in social cognitive disorders and emotional dysregulation.