The striatum consists of two anatomically and neurochemically distinct compartments, striosomes and the matrix, which receive dopaminergic inputs from the midbrain and exhibit distinct dopamine release dynamics in acute brain slices. Striosomes comprise approximately 15 % of the striatum by volume and are distributed mosaically. Therefore, it is difficult to selectively record dopamine dynamics in striosomes using traditional neurochemical measurements in behaving animals, and it is unclear whether distinct dynamics play a role in associative learning. In this study, we used transgenic mice selectively expressing Cre in striosomal neurons, combined with a fiber photometry technique, to selectively record dopamine release in striosomes during classical conditioning. Water-restricted mice could distinguish the conditioned stimulus (CS) associated with saccharin water from the air-puff-associated CS. The air-puff-associated CS evoked phasic dopamine release only in striosomes. Furthermore, air puff presentation induced dopamine release to striosomal neurons but suppressed release to striatal neurons non-selectively recorded. These findings suggest that dopamine is released in a differential manner in striosomes and the matrix in behaving animals and that dopamine release in striosomes is preferentially induced by the air-puff-associated CS and air puff presentation. These findings support the hypothesis that striosomal neurons play a dominant role in aversive stimuli prediction.

Chemogenetics uses artificially-engineered proteins to modify the activity of cells, notably neurons, in response to small molecules. Although a common set of chemogenetic tools are the G protein-coupled receptor-based DREADDs, there has been great hope for ligand-gated, ion channel-type chemogenetic tools that directly impact neuronal excitability. We have devised such a technology by exploiting insect Ionotropic Receptors (IRs), a highly divergent subfamily of ionotropic glutamate receptors that evolved to detect diverse environmental chemicals. Here, we review a series of studies developing and applying this "IR-mediated neuronal activation" (IRNA) technology with the Drosophila melanogaster IR84a/IR8a complex, which detects phenyl-containing ligands. We also discuss how variants of IRNA could be produced by modifying the composition of the IR complex, using natural or engineered subunits, which would enable artificial activation of different cell populations in the brain in response to distinct chemicals.

Perform ance decrement under excessive psychological pressure is known as "choking," yet its mechanisms and neural foundations remain underexplored. Hypothesizing that changes in the internal model could induce choking, we conducted a 7T functional MRI introducing excessive pressure through a rare Jackpot condition that offers high rewards for successful performance. Twenty-nine volunteers underwent a visual reaching task. We monitored practice and main sessions to map the task's internal model through learning. Participants were pre-informed of four potential reward conditions upon success at the beginning of the main session task. The success rates in the Jackpot condition were significantly lower than in other conditions, indicative of choking. During the preparation phase, activations in the cerebellum and the middle temporal visual area (hMT+) were associated with Jackpot-specific failures. The cluster in the cerebellar hemisphere overlapped with the internal model regions identified by a learning-related decrease in activation during the practice session. We observed task-specific functional connectivity between the cerebellum and hMT+. These findings suggest a lack of sensory attenuation when an internal model predicting the outcome of one's actions is preloaded during motor preparation. Within the active inference framework of motor control, choking stems from the cerebellum's internal model modulation by psychological pressure, manifested through improper sensory attenuation.

Temperature is a constant environmental factor on Earth, acting as a continuous stimulus that organisms must constantly perceive to survive. Organisms possess neural systems that receive various types of environmental information, including temperature, and mechanisms for adapting to their surroundings. This paper provides insights into the neural circuits and intertissue networks involved in physiological temperature responses, specifically the mechanisms of "cold tolerance" and "temperature acclimation," based on an analysis of the nematode Caenorhabditis elegans as an experimental system for neural and intertissue information processing.

NMDA and AMPA receptors are co-localized at most glutamatergic synapses, where their numbers and distribution undergo dynamic changes. Glutamate binds to both the NMDA and AMPA receptors. Initially, I investigated whether there is competition between AMPA receptors and N-methyl-D-aspartic acid (NMDA) receptors for glutamate. Subsequently, I examined how these dynamic receptor changes affect synaptic response. To test the hypothesis, a synaptic model incorporating coexisting NMDA and AMPA receptors within the postsynaptic density (PSD) was developed. During long-term potentiation (LTP) induction, the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors in the PSD increase. If there is competition for glutamate between AMPA receptors and NMDA receptors, the number of activated NMDA receptor channels will decrease. Since LTP induction relies on the activation of NMDA receptors, reducing their activation will raise the threshold for LTP induction. Consequently, the LTP of the synapse itself can establish negative feedback, preventing excessive dynamics and maintaining the stability of the neural network.

Infrared laser stimulation of the cochlea has been proposed as a possible alternative to conventional auditory prostheses. Whereas previous studies have focused primarily on the short-term effects of laser stimulation, the practical application of this technics requires an investigation into whether prolonged laser exposure can induce neural responses and safely. This study assessed the effect of laser-induced damage to the cochlea on auditory perception using Mongolian gerbils (Meriones unguiculatus) trained with a classical conditioning task. The broadband noise was presented as a conditioned stimulus, and reward licking was recorded as a conditioned response. After training, the subject's cochlea was exposed to a continuous pulsed laser for 15 h. Broadband noise of various intensities was presented without pairing it with water before and after laser exposure to assess the decrease in auditory perception due to laser-induced injury. The licking rate did not change after laser exposure of 6.6 W/cm or weaker but drastically decreased after 26.4 W/cm or higher. These findings showed, for the first time, that the safety margin of long-term, at least several hours, cochlear laser stimulation exists and will contribute to the appropriate delimitation of the safe and effective laser stimulation parameters in future research.

In human walking, the legs and other body parts coordinate to produce a rhythm with appropriate phase relationships. From the point of view for rehabilitating gait disorders, such as Parkinson Disorders, it is important to understand the control mechanism of the gait rhythm. A previous study showed that the antiphase relationship of the two legs during walking is not strictly controlled using the reduction of the motion of the legs during walking to coupled phase oscillators. However, the control mechanisms other than those of the legs remains unknown. In particular, the trunk moves in tandem with the legs and must play an important role in stabilizing walking because it is above the legs and accounts for more than half of the mass of the human body. This study aims to uncover the control mechanism of the leg-trunk coordination in the sagittal plane using the coupled phase oscillators model and Bayesian estimation. We demonstrate that the leg-trunk coordination is not strictly controlled, as well as the interleg coordination.

Previously, the integration of comparative biological and neuroscientific approaches has led to significant advancements in social neuroscience. This review highlights the potential and future directions of evolutionary social neuroscience research utilizing medaka fishes (the family Adrianichthyidae) including Japanese medaka (Oryzias latipes). We focus on medaka social cognitive capabilities and mate choice behavior, particularly emphasizing mate preference using visual cues. Medaka fishes are also advantageous due to their abundant genetic resources, extensive genomic information, and the relative ease of laboratory breeding and genetic manipulation. Here we present some research examples of both the conventional neuroscience approach and evolutionary approach involving medaka fishes and other species. We also discuss the prospects of uncovering the molecular and cellular mechanisms underlying the diversity of visual mate preference among species. Especially, we introduce that the single-cell transcriptome technology, particularly in conjunction with 'Adaptive Circuitry Census', is an innovative tool that bridges comparative biological methods and neuroscientific approaches. Evolutionary social neuroscience research using medaka has the potential to unveil fundamental principles in neuroscience and elucidate the mechanisms responsible for generating diversity in mating strategies.

Huntington's disease (HD) is a neurodegenerative disorder characterized by the presence of abnormally expanded polyglutamine tracts in huntingtin protein (HTT). Mutant HTT disrupts synaptic transmission and plasticity, particularly in the striatum and cortex, leading to early dysfunctions, such as altered neurotransmitter release, impaired synaptic vesicle recycling, and disrupted postsynaptic receptor function. Synaptic loss precedes neuronal degeneration and contributes to disease progression. Neurexin1 (NRXN1), a synaptic cell adhesion molecule primarily located in the presynaptic membrane, plays a crucial role in maintaining synaptic integrity. The present study investigated the role of NRXN1 in HD. This study researched whether the changed level has been related to expanded polyQ stretch and disease progression. Here, we report a reduction in NRXN1 levels in post-symptomatic HD mice and in neuronal cells expressing abnormally expanded polyQ tracts. Mutant HTT was found to decrease NRXN1 levels while increasing LAMP2A levels, which promotes lysosomal degradation of NRXN1. In HD cells expressing Q111, downregulated LAMP2A restored NRXN1 levels and maintained cell proliferation compared with cells expressing Q7. These findings suggest that NRXN1 is regulated by LAMP2A-mediated way and that decreased NRXN1 levels are associated with symptomatic progression and neuronal cell loss in HD.

The pancreatic peptide amylin promotes negative energy balance in part through activation of amylin receptors (AmyRs) expressed in the ventral tegmental area (VTA), but studies have been limited to male rodents. We evaluated whether VTA amylin signaling governs feeding and body weight in female rats. Indeed, pharmacological VTA AmyR activation suppressed chow intake and body weight in females. Viral-mediated knockdown of VTA calcitonin receptor (GPCR of AmyR) supports the physiological relevance of VTA amylin signaling for energy balance control in females. Collectively, these data support the relevance of VTA amylin signaling for energy balance control in both sexes.

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.

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.

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.

Operant learning is a behavioral paradigm where animals learn to associate their actions with consequences, adapting their behavior accordingly. This review delves into the neural circuits that underpin operant learning in rodents, emphasizing the dynamic interplay between neural pathways, synaptic plasticity, and gene expression changes. We explore the cortico-basal ganglia circuits, highlighting the pivotal role of dopamine in modulating these pathways to reinforce behaviors that yield positive outcomes. We include insights from recent studies, which reveals the intricate roles of midbrain dopamine neurons in integrating action initiation and reward feedback, thereby enhancing movement-related activities in the dorsal striatum. Additionally, we discuss the molecular diversity of striatal neurons and their specific roles in reinforcement learning. The review also covers advances in transcriptome analysis techniques, such as single-cell RNA sequencing, which have provided deeper insights into the gene expression profiles associated with different neuronal populations during operant learning.

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 article presents a mini-review about the progress in inferring monosynaptic connections from spike trains of multiple neurons over the past twenty years. First, we explain a variety of meanings of "neuronal connectivity" in different research areas of neuroscience, such as structural connectivity, monosynaptic connectivity, and functional connectivity. Among these, we focus on the methods used to infer the monosynaptic connectivity from spike data. We then summarize the inference methods based on two main approaches, i.e., correlation-based and model-based approaches. Finally, we describe available source codes for connectivity inference and future challenges. Although inference will never be perfect, the accuracy of identifying the monosynaptic connections has improved dramatically in recent years due to continuous efforts.

Epilepsy is a major neurological disorder characterized by recurrent, spontaneous seizures. For patients with drug-resistant epilepsy, treatments include neurostimulation or surgical removal of the epileptogenic zone (EZ), the brain region responsible for seizure generation. Precise targeting of the EZ requires reliable biomarkers. Spike ripples - high-frequency oscillations that co-occur with large amplitude epileptic discharges - have gained prominence as a candidate biomarker. However, spike ripple detection remains a challenge. The gold-standard approach requires an expert manually visualize and interpret brain voltage recordings, which limits reproducibility and high-throughput analysis. Addressing these limitations requires more objective, efficient, and automated methods for spike ripple detection, including approaches that utilize deep neural networks. Despite advancements, dataset heterogeneity and scarcity severely limit machine learning performance. Our study explores long-short term memory (LSTM) neural network architectures for spike ripple detection, leveraging data augmentation to improve classifier performance. We highlight the potential of combining training on augmented and in vivo data for enhanced spike ripple detection and ultimately improving diagnostic accuracy in epilepsy treatment.

Transcription factors (TFs) regulate the establishment and modulation of the transcriptome within cells, thereby playing a crucial role in various aspects of cellular physiology throughout the body. Quantitative measurement of TF activity during the development, function, and dysfunction of the brain is essential for gaining a deeper understanding of the regulatory mechanisms governing gene expression during these processes. Due to their role as regulators of gene expression, assessing and modulating detailed TF activity contributes to the development of practical methods to intervene in these processes, potentially offering more efficient treatments for diseases. Recent methodologies have revealed that TF activity is dynamically regulated within cells and organisms, including the adult brain. This review summarizes the regulatory mechanisms of TF activities and the methodologies used to assess them, emphasizing their importance in both fundamental research and clinical applications.

Environmental factors have well-documented impacts on brain development and mental health. Therefore, it is crucial to employ a reliable assay system to assess the spatial preference of model animals. In this study, we introduced an unbiased quadrant chamber assay system and discovered that parental pup-gathering behavior takes place in a very efficient manner. Furthermore, we found that test mice exhibited preferences for specific environments in both spontaneous and parental pup-gathering behavior contexts. Notably, the spatial preferences of autism spectrum disorder model animals were initially suppressed but later equalized during the spontaneous behavior assay, accompanied by increased time spent in the preferred chamber. In conclusion, our novel quadrant chamber assay system provides an ideal platform for investigating the spatial preference of mice, offering potential applications in studying environmental impacts and exploring neurodevelopmental and psychiatric disorder models.

This study aimed to elucidate the expression patterns of miR-33 and ARC in both a rat model of temporal lobe epilepsy (TLE) and human TLE patients, to explore the role of miR-33 in epilepsy onset through its regulation of ARC expression in the hippocampus. Our findings, supported by a Dual-Luciferase reporter assay, suggest that miR-33 can bind to the 3' UTR region of ARC. We observed that miR-33 levels were reduced at 1 hour and 60 days post-seizure, while ARC expression notably increased at these time points. In the hippocampal CA1 and CA3 regions of post-seizure rats, ARC expression significantly exceeded that of control groups. Following the transfection of HEK cells with a miR-33 mimic, there was a decrease in both ARC mRNA and protein levels, whereas the group treated with a miR-33 inhibitor displayed the opposite effect. RNA sequencing in TLE patients revealed a similar miR-33 and ARC interaction. The regulation of Arc expression by miR-33 suggests that Arc may be a target gene of miR-33 in the context of epilepsy. Our findings indicate that miR-33 downregulation could contribute to the dysregulation of Arc expression observed in TLE, potentially influencing the disease process. Further studies are required to establish the exact role of miR-33-mediated Arc regulation in the development of epilepsy.