{"title":"Dopamine release in striatal striosome compartments in response to rewards and aversive outcomes during classical conditioning in mice","authors":"Tomohiko Yoshizawa, Makoto Funahashi","doi":"10.1016/j.neures.2024.11.002","DOIUrl":"10.1016/j.neures.2024.11.002","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 61-68"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Human induced pluripotent stem cell-derived dopaminergic neurons release alpha-synuclein through neuronal activity","authors":"Maierdanjiang Nuermaimaiti , Kei-ichi Ishikawa , Genko Oyama , Risa Nonaka , Takahiro Shiga , Takayuki Jo , Taiji Tsunemi , Ryota Nakamura , Rejko Krüger , Wado Akamatsu , Nobutaka Hattori","doi":"10.1016/j.neures.2024.11.007","DOIUrl":"10.1016/j.neures.2024.11.007","url":null,"abstract":"<div><div>Lewy body diseases, including Parkinson's disease (PD), are characterized by the spread of alpha-synuclein (αSyn) between neurons across synapses, a process crucial for understanding their pathophysiology and developing effective treatments. In this study, we aimed to investigate the role of neuronal activity in releasing αSyn from human induced pluripotent stem cell-derived dopaminergic neurons. We examined human induced pluripotent stem cell-derived dopaminergic neurons, both healthy and those with the αSyn gene mutation associated with PD. We employed pharmacological agents and optogenetic techniques and demonstrated that increased neuronal activity, induced by bicuculline or optogenetic stimulation, significantly enhances αSyn release. However, suppression of neuronal activity with cyanquixaline reduces αSyn secretion. These findings underscore the pivotal role of neuronal activity in αSyn transmission between neurons, showing its potential impact on the spread of Lewy pathology in patients with neurodegenerative diseases like PD. Therefore, this study advances our understanding of PD and opens new avenues for therapeutic strategies to mitigate Lewy body disease progression.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 105-114"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142770440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatial dynamics of spontaneous activity in the developing and adult cortices","authors":"Tomonari Murakami","doi":"10.1016/j.neures.2024.12.002","DOIUrl":"10.1016/j.neures.2024.12.002","url":null,"abstract":"<div><div>Even in the absence of external stimuli, the brain remains remarkably active, with neurons continuously firing and communicating with each other. It is not merely random firing of individual neurons but rather orchestrated patterns of activity that propagate throughout the intricate network. Over two decades, advancements in neuroscience observation tools for hemodynamics, membrane potential, and neural calcium signals, have allowed researchers to analyze the dynamics of spontaneous activity across different spatial scales, from individual neurons to macroscale brain networks. One of the remarkable findings from these studies is that the spatial patterns of spontaneous activity in the developing brain are vastly different from those in the mature adult brain. Spatial patterns of spontaneous activity during development are essential for connection refinement between brain regions, whereas the functional role in the adult brain is still controversial. In this paper, I review the differences in spatial dynamics of spontaneous activity between developing and adult cortices. Then, I delve into the cellular mechanisms underlying spontaneous activity, especially its generation and propagation manner, to contribute to a deeper understanding of brain function and its development.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 1-10"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142801771","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Aya Okamoto , Miku Uenaka , Yuki Ito , Yuta Kuroki , Tomohiro Miyasaka , Koji Toda , Shizuko Hiryu , Kohta I. Kobayasi , Yuta Tamai
{"title":"Safety evaluations for transtympanic laser stimulation of the cochlea in Mongolian gerbils (Meriones unguiculatus)","authors":"Aya Okamoto , Miku Uenaka , Yuki Ito , Yuta Kuroki , Tomohiro Miyasaka , Koji Toda , Shizuko Hiryu , Kohta I. Kobayasi , Yuta Tamai","doi":"10.1016/j.neures.2024.10.004","DOIUrl":"10.1016/j.neures.2024.10.004","url":null,"abstract":"<div><div>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 (<em>Meriones unguiculatus</em>) 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<sup>2</sup> or weaker but drastically decreased after 26.4 W/cm<sup>2</sup> 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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 31-40"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142504801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tyler J. Gustafson , Lauren E. McGrath , Matthew R. Hayes , Elizabeth G. Mietlicki-Baase
{"title":"Ventral tegmental area amylin / calcitonin receptor signaling suppresses feeding and weight gain in female rats","authors":"Tyler J. Gustafson , Lauren E. McGrath , Matthew R. Hayes , Elizabeth G. Mietlicki-Baase","doi":"10.1016/j.neures.2024.10.001","DOIUrl":"10.1016/j.neures.2024.10.001","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 136-139"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142400833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neurexin1 level in Huntington’s Disease and decreased Neurexin1 in disease progression","authors":"Kyoungjoo Cho , Gyung Whan Kim","doi":"10.1016/j.neures.2024.10.006","DOIUrl":"10.1016/j.neures.2024.10.006","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 97-104"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Quantitative analysis of the interaction between NMDA and AMPA receptors in glutamatergic synapses based on mathematical model","authors":"Qingchen Guo","doi":"10.1016/j.neures.2024.10.003","DOIUrl":"10.1016/j.neures.2024.10.003","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 127-135"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142470822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Neural substrates of choking under pressure: A 7T-fMRI study","authors":"Kanae Ogasawara , Takahiko Koike , Masaki Fukunaga , Ayumi Yoshioka , Tetsuya Yamamoto , Norihiro Sadato","doi":"10.1016/j.neures.2024.11.004","DOIUrl":"10.1016/j.neures.2024.11.004","url":null,"abstract":"<div><div>Performance 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 7 T 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 <strong>(</strong>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.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 41-60"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142639226","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Detailed analysis of drift diffusion model parameters estimated for the ultimatum game","authors":"Shotaro Numano , Masahiko Haruno","doi":"10.1016/j.neures.2024.12.003","DOIUrl":"10.1016/j.neures.2024.12.003","url":null,"abstract":"<div><div>Bargaining is fundamental in human social interactions and often studied using the ultimatum game, where a proposer offers a division of resources, and the responder decides whether to accept or reject it. If accepted, the resources are divided as proposed, but neither party receives anything otherwise. While previous research has typically focused on either the choice or response time, a computational approach that integrates both can provide deeper insights into the cognitive and neural processes involved. Although the drift diffusion model (DDM) has been used for this purpose, few studies have tested it in the context of the ultimatum game. Here, we collected participants' behaviors as a responder during the ultimatum game (n = 71) and analyzed them using a Bayesian version of DDM. The best (estimated) model included parameters for non-decision time, boundary separation, bias, and drift, with drift expressed as a linear combination of self-reward, advantageous inequity, and disadvantageous inequity. This model accurately replicated participants' choices and response times. Our analysis revealed that the drift parameter represents trial-by-trial choices and response times, while other parameters represent average rejection rates and response times. We also found that boundary separation and bias exhibited a more complex interaction than previously recognized. Thus, this study provides important insights into the application of DDM to studies on neural analysis during human bargaining behavior.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 115-126"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142792137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Masatoshi Nishimura , Tomoki Kodera , Shota Adachi , Akinori Y. Sato , Ryosuke F. Takeuchi , Hiroshi Nonaka , Itaru Hamachi , Fumitaka Osakada
{"title":"Conversion of silent synapses to AMPA receptor-mediated functional synapses in human cortical organoids","authors":"Masatoshi Nishimura , Tomoki Kodera , Shota Adachi , Akinori Y. Sato , Ryosuke F. Takeuchi , Hiroshi Nonaka , Itaru Hamachi , Fumitaka Osakada","doi":"10.1016/j.neures.2024.12.008","DOIUrl":"10.1016/j.neures.2024.12.008","url":null,"abstract":"<div><div>Despite the crucial role of synaptic connections and neural activity in the development and organization of cortical circuits, the mechanisms underlying the formation of functional synaptic connections in the developing human cerebral cortex remain unclear. We investigated the development of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR)-mediated synaptic transmission using human cortical organoids (hCOs) derived from induced pluripotent stem cells. Two-photon Ca<sup>2</sup>⁺ imaging revealed an increase in the frequency and amplitude of spontaneous activity in hCOs on day 80 compared to day 50. Additionally, spontaneous neural activity in late-stage hCOs, but not in early-stage hCOs, was blocked by N-methyl-D-aspartate receptor (NMDAR) and AMPAR antagonists. However, transsynaptic circuit tracing with G-deleted rabies viral vectors indicated a similar number of synaptic connections in early- and late-stage hCOs. Notably, chemical labeling demonstrated a significant increase in AMPAR expression on the postsynaptic membrane and colocalization with NMDARs in late-stage hCOs. These results suggest that hCOs progressively organize excitatory synaptic transmission, concurrent with the transition from silent synapses lacking AMPARs to functional synapses containing NMDARs and AMPARs. This <em>in vitro</em> model of human cortical circuits derived from induced pluripotent stem cells reflects the developmental programs underlying physiological transitions, providing valuable insights into human corticogenesis and neurodevelopmental disorders.</div></div>","PeriodicalId":19146,"journal":{"name":"Neuroscience Research","volume":"212 ","pages":"Pages 20-30"},"PeriodicalIF":2.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}