Pub Date : 2026-01-28DOI: 10.1523/JNEUROSCI.1490-25.2025
Emily Wiecek, Luis D Ramirez, Michaela Klimova, Sam Ling
Our visual system can recognize patterns across many spatial scales. A fundamental assumption in visual neuroscience is that this ability relies on the putative scale-invariant properties of receptive fields (RFs) in early vision, whereby the spatial area over which a visual neuron responds is proportional to the spatial scale of information it can encode (i.e., spatial frequency, SF). In other words, the resolution of spatial sampling of a RF is assumed to be constant in the visual cortex. However, this assumption has gone untested in the human visual cortex. To address this, we leveraged model-based fMRI techniques that characterize the spatial tuning and SF preferences of cortical subpopulations sampled within a voxel across eight participants (five females, three males). We find that the voxel-wise ratio between peak SF tuning and RF size-expressed as "cycles per RF"-remains constant across visual areas V1, V2, and V3, suggesting that, at the population level, SF preferences are inversely proportional to the RF size, a tenet of scale invariance in early human vision.
{"title":"Spatial Frequency Tuning Follows Scale Invariance in the Human Visual Cortex.","authors":"Emily Wiecek, Luis D Ramirez, Michaela Klimova, Sam Ling","doi":"10.1523/JNEUROSCI.1490-25.2025","DOIUrl":"10.1523/JNEUROSCI.1490-25.2025","url":null,"abstract":"<p><p>Our visual system can recognize patterns across many spatial scales. A fundamental assumption in visual neuroscience is that this ability relies on the putative scale-invariant properties of receptive fields (RFs) in early vision, whereby the spatial area over which a visual neuron responds is proportional to the spatial scale of information it can encode (i.e., spatial frequency, SF). In other words, the resolution of spatial sampling of a RF is assumed to be constant in the visual cortex. However, this assumption has gone untested in the human visual cortex. To address this, we leveraged model-based fMRI techniques that characterize the spatial tuning and SF preferences of cortical subpopulations sampled within a voxel across eight participants (five females, three males). We find that the voxel-wise ratio between peak SF tuning and RF size-expressed as \"cycles per RF\"-remains constant across visual areas V1, V2, and V3, suggesting that, at the population level, SF preferences are inversely proportional to the RF size, a tenet of scale invariance in early human vision.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853248/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004491","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-28DOI: 10.1523/JNEUROSCI.0180-25.2025
Evan A Kattner, Terrence R Stanford, Emilio Salinas
Visuospatial attention is key for parsing visual information and selecting targets to look at. Based on regimented laboratory tasks, it is now well-established that three types of mechanism determine when and where attention is deployed; these are stimulus-driven (exogenous), goal-driven (endogenous), and history-driven (reflecting recent experience). It is unclear, however, how these distinct attentional signals interact and contribute in visual environments that are more akin to natural scanning, when stimuli may change rapidly and no fixation requirements are imposed. Here, we investigate this via a gamified task in which participants (male and female) make continuous saccadic choices at a rapid pace-and yet, perceptual performance can be accurately tracked over time as the choice process unfolds. The results reveal unequivocal markers of exogenous capture toward salient stimuli; endogenous guidance toward valuable targets and relevant locations; and history-driven effects, which produce large, involuntary modulations in processing capacity. Under dynamic conditions, success probability is dictated by temporally precise interplay between different forms of spatial attention, with recent history making a particularly prominent contribution.
{"title":"Contributions of Distinct Attention Mechanisms to Saccadic Choices in a Gamified, Dynamic Environment.","authors":"Evan A Kattner, Terrence R Stanford, Emilio Salinas","doi":"10.1523/JNEUROSCI.0180-25.2025","DOIUrl":"10.1523/JNEUROSCI.0180-25.2025","url":null,"abstract":"<p><p>Visuospatial attention is key for parsing visual information and selecting targets to look at. Based on regimented laboratory tasks, it is now well-established that three types of mechanism determine when and where attention is deployed; these are stimulus-driven (exogenous), goal-driven (endogenous), and history-driven (reflecting recent experience). It is unclear, however, how these distinct attentional signals interact and contribute in visual environments that are more akin to natural scanning, when stimuli may change rapidly and no fixation requirements are imposed. Here, we investigate this via a gamified task in which participants (male and female) make continuous saccadic choices at a rapid pace-and yet, perceptual performance can be accurately tracked over time as the choice process unfolds. The results reveal unequivocal markers of exogenous capture toward salient stimuli; endogenous guidance toward valuable targets and relevant locations; and history-driven effects, which produce large, involuntary modulations in processing capacity. Under dynamic conditions, success probability is dictated by temporally precise interplay between different forms of spatial attention, with recent history making a particularly prominent contribution.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12853255/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145679289","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-23DOI: 10.1523/jneurosci.1580-25.2026
Thomas M Morin,Jordyn L Cowan,Hsiang-Yu Chen,Jourdan H Parent,Jennifer L Crawford,Claire J Ciampa,Vyoma D Shah,Ming Hsu,William J Jagust,Anne S Berry
Aging is accompanied by the disruption of multiple neural systems including alteration in dopamine neurotransmission as well as through the accumulation of neuropathology. Despite broad appreciation that complex mental function relies on integration across systems, there is a general lack of understanding of how multiple age and disease-related brain features interact to drive variation in performance. To address this gap, we used positron emission tomography in male and female humans to examine independent and combined impacts of dopamine synthesis capacity ([18F]Fluoro-L-m-tyrosine) and Alzheimer's disease (AD)-related pathology (amyloid-β: [11C]Pittsburgh Compound B; tau: [18F]Flortaucipir) on memory for rewarding events, which we assessed using functional magnetic resonance imaging (n = 80 young and older adults). We specifically probed dopamine synthesis capacity given evidence that it is upregulated in older age, and may impart resilience to age-related neural losses. In young adults, higher dopamine synthesis capacity was associated with superior overall memory and greater temporal lobe activation. In older adults, neither dopamine nor AD pathology independently predicted memory performance, though higher dopamine synthesis capacity was associated with memory biases for stimuli associated with rewards rather than losses. Instead, we observed interactions between dopamine synthesis and pathology whereby only older adults with minimal pathology showed preservation of positive dopamine-memory associations. In contrast to resilience accounts, the presence of AD pathology disrupted and even reversed relationships between dopamine synthesis, memory, and temporal lobe activation. These results suggest that AD pathological processes acutely alter the mechanisms by which elevated dopamine synthesis supports optimal memory performance.Significance Statement While there is compelling evidence that aging is associated with concomitant alterations in dopamine function and cognition, studies directly linking individual differences in endogenous dopamine with memory performance in older age have shown mixed results. We find that the presence of amyloid-β and tau pathology significantly alters relationships among in vivo measures of dopamine synthesis capacity, brain activity, and behavior such that episodic memory performance appears to be relatively decoupled from the dopamine system in the context of preclinical Alzheimer's disease. These findings suggest that it is critical to account for pathological disease processes when considering the mechanisms by which dopamine influences cognitive function, and have implications for understanding the efficacy of therapeutic interventions targeting the dopamine system.
衰老伴随着多个神经系统的破坏,包括多巴胺神经传递的改变,以及神经病理学的积累。尽管人们普遍认识到复杂的心理功能依赖于跨系统的整合,但人们普遍缺乏对多种年龄和疾病相关的大脑特征如何相互作用以驱动表现变化的理解。为了解决这一差距,我们使用正电子发射断层扫描技术在男性和女性中检测多巴胺合成能力([18F]氟- l -m-酪氨酸)和阿尔茨海默病(AD)相关病理(淀粉样蛋白-β: [11C]匹兹堡化合物B; tau: [18F]Flortaucipir)对奖励事件记忆的独立和联合影响,我们使用功能磁共振成像(n = 80名年轻人和老年人)对其进行了评估。我们特别研究了多巴胺合成能力,因为有证据表明,多巴胺合成能力在老年人中上调,并可能赋予与年龄相关的神经损失的弹性。在年轻人中,更高的多巴胺合成能力与更好的整体记忆和更大的颞叶激活有关。在老年人中,多巴胺和AD病理都不能独立预测记忆表现,尽管较高的多巴胺合成能力与奖励相关的刺激的记忆偏差有关,而不是损失。相反,我们观察到多巴胺合成和病理之间的相互作用,只有最小病理的老年人表现出积极的多巴胺-记忆关联的保存。与恢复力的说法相反,阿尔茨海默病的存在破坏甚至逆转了多巴胺合成、记忆和颞叶激活之间的关系。这些结果表明,阿尔茨海默病的病理过程急剧改变了多巴胺合成升高支持最佳记忆表现的机制。虽然有令人信服的证据表明,衰老与多巴胺功能和认知的伴随改变有关,但直接将内源性多巴胺的个体差异与老年人的记忆表现联系起来的研究显示,结果好坏参半。我们发现淀粉样蛋白-β和tau病理的存在显著改变了体内多巴胺合成能力、大脑活动和行为之间的关系,因此在临床前阿尔茨海默病的背景下,情景记忆表现似乎与多巴胺系统相对脱钩。这些发现表明,在考虑多巴胺影响认知功能的机制时,考虑病理疾病过程是至关重要的,并且对理解针对多巴胺系统的治疗干预的有效性具有重要意义。
{"title":"Alzheimer's disease pathologies affect dopaminergic neural mechanisms of memory.","authors":"Thomas M Morin,Jordyn L Cowan,Hsiang-Yu Chen,Jourdan H Parent,Jennifer L Crawford,Claire J Ciampa,Vyoma D Shah,Ming Hsu,William J Jagust,Anne S Berry","doi":"10.1523/jneurosci.1580-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1580-25.2026","url":null,"abstract":"Aging is accompanied by the disruption of multiple neural systems including alteration in dopamine neurotransmission as well as through the accumulation of neuropathology. Despite broad appreciation that complex mental function relies on integration across systems, there is a general lack of understanding of how multiple age and disease-related brain features interact to drive variation in performance. To address this gap, we used positron emission tomography in male and female humans to examine independent and combined impacts of dopamine synthesis capacity ([18F]Fluoro-L-m-tyrosine) and Alzheimer's disease (AD)-related pathology (amyloid-β: [11C]Pittsburgh Compound B; tau: [18F]Flortaucipir) on memory for rewarding events, which we assessed using functional magnetic resonance imaging (n = 80 young and older adults). We specifically probed dopamine synthesis capacity given evidence that it is upregulated in older age, and may impart resilience to age-related neural losses. In young adults, higher dopamine synthesis capacity was associated with superior overall memory and greater temporal lobe activation. In older adults, neither dopamine nor AD pathology independently predicted memory performance, though higher dopamine synthesis capacity was associated with memory biases for stimuli associated with rewards rather than losses. Instead, we observed interactions between dopamine synthesis and pathology whereby only older adults with minimal pathology showed preservation of positive dopamine-memory associations. In contrast to resilience accounts, the presence of AD pathology disrupted and even reversed relationships between dopamine synthesis, memory, and temporal lobe activation. These results suggest that AD pathological processes acutely alter the mechanisms by which elevated dopamine synthesis supports optimal memory performance.Significance Statement While there is compelling evidence that aging is associated with concomitant alterations in dopamine function and cognition, studies directly linking individual differences in endogenous dopamine with memory performance in older age have shown mixed results. We find that the presence of amyloid-β and tau pathology significantly alters relationships among in vivo measures of dopamine synthesis capacity, brain activity, and behavior such that episodic memory performance appears to be relatively decoupled from the dopamine system in the context of preclinical Alzheimer's disease. These findings suggest that it is critical to account for pathological disease processes when considering the mechanisms by which dopamine influences cognitive function, and have implications for understanding the efficacy of therapeutic interventions targeting the dopamine system.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"1 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/JNEUROSCI.0929-25.2025
James Bigelow, Toshiaki Suzuki, Yulang Wu, Ying Hu, Andrea R Hasenstaub
Recent studies suggest some hippocampal (HC) neurons respond to passively presented sounds in naive subjects, but the specificity and prevalence of these responses remain unclear. We used Neuropixels probes to record unit activity across layers in mid-ventral HC and auditory cortex (ACtx) of awake, untrained mice (male and female) while presenting diverse sounds at typical environmental levels (65-70 dB SPL). A subset of HC neurons exhibited reliable, short latency responses to passive sounds, including tones and broadband noise. HC units showed evidence of tuning for tone frequency but not spectrotemporal features in continuous dynamic moving ripples. Across sound types, HC responses overwhelmingly occurred at stimulus onset; they quickly adapted to continuous sounds and did not respond at sound offset. Among all sounds tested, broadband noise was most effective at driving HC activity. Spectral manipulations indicated response prevalence scaled with increasing spectral bandwidth and density. Similar responses were also observed for visual flash and contrast-modulated noise movies, although these were less common than for broadband noise. Sound-evoked face movements, quantified by total face motion energy (FME), correlated with population-level HC activity. However, many individual units responded regardless of FME strength, suggesting both auditory and motor-correlated inputs. Together, our results show that abrupt sound onsets are sufficient to activate many HC neurons in the absence of learning or behavioral engagement. This supports a role for HC in detecting salient environmental changes and supports the idea that auditory inputs contribute directly to HC function.
最近的研究表明,在naïve受试者中,一些海马(HC)神经元对被动呈现的声音有反应,但这些反应的特异性和普遍性尚不清楚。在典型环境水平(65-70 dB SPL)下呈现不同声音时,我们使用神经像素探针记录醒着的未训练小鼠(雄性和雌性)中腹侧HC和听觉皮层(ACtx)各层的单位活动。HC神经元的一个子集对被动声音(包括音调和宽带噪声)表现出可靠的、短延迟的反应。HC单元在连续动态移动的波纹中显示音调频率调谐的证据,而不是光谱时间特征。在各种声音类型中,HC反应绝大多数发生在刺激开始时;它们很快适应了连续的声音,对声音偏移没有反应。在所有被测试的声音中,宽带噪声对驱动HC活动最有效。光谱操作表明,响应率随光谱带宽和密度的增加而增加。类似的反应也被观察到视觉闪光和对比度调制噪声电影,尽管这些不像宽带噪声那么常见。声音诱发的面部运动,通过总面部运动能量(FME)量化,与人群水平的HC活动相关。然而,无论FME强度如何,许多个体单位都做出了反应,这表明听觉和运动相关的输入都存在。总之,我们的研究结果表明,在没有学习或行为参与的情况下,突然的声音发作足以激活许多HC神经元。这支持了HC在检测显著环境变化中的作用,并支持了听觉输入直接促进HC功能的观点。海马体对学习和记忆至关重要,但其在感觉加工中的作用尚不清楚。在这里,我们展示了清醒的、未经训练的老鼠的许多海马神经元对被动声音,尤其是宽带噪声有反应。声音启动-从沉默到声音的过渡-对这些反应至关重要,这表明它在检测突然的,显著的环境变化方面起作用。与这种可能性相一致的是,一些单位也对视觉事件做出反应,尽管对噪音的反应较少。与听觉皮层相比,海马体单元不可靠地调谐光谱时间调制特征,表明独立的功能角色。海马体中被动听觉加工的普遍存在建立在先前的研究基础上,该研究表明听力可能与一般认知健康相互作用。
{"title":"Survey of Hippocampal Responses to Sound in Naive Mice Reveals Widespread Activation by Broadband Noise Onsets.","authors":"James Bigelow, Toshiaki Suzuki, Yulang Wu, Ying Hu, Andrea R Hasenstaub","doi":"10.1523/JNEUROSCI.0929-25.2025","DOIUrl":"10.1523/JNEUROSCI.0929-25.2025","url":null,"abstract":"<p><p>Recent studies suggest some hippocampal (HC) neurons respond to passively presented sounds in naive subjects, but the specificity and prevalence of these responses remain unclear. We used Neuropixels probes to record unit activity across layers in mid-ventral HC and auditory cortex (ACtx) of awake, untrained mice (male and female) while presenting diverse sounds at typical environmental levels (65-70 dB SPL). A subset of HC neurons exhibited reliable, short latency responses to passive sounds, including tones and broadband noise. HC units showed evidence of tuning for tone frequency but not spectrotemporal features in continuous dynamic moving ripples. Across sound types, HC responses overwhelmingly occurred at stimulus onset; they quickly adapted to continuous sounds and did not respond at sound offset. Among all sounds tested, broadband noise was most effective at driving HC activity. Spectral manipulations indicated response prevalence scaled with increasing spectral bandwidth and density. Similar responses were also observed for visual flash and contrast-modulated noise movies, although these were less common than for broadband noise. Sound-evoked face movements, quantified by total face motion energy (FME), correlated with population-level HC activity. However, many individual units responded regardless of FME strength, suggesting both auditory and motor-correlated inputs. Together, our results show that abrupt sound onsets are sufficient to activate many HC neurons in the absence of learning or behavioral engagement. This supports a role for HC in detecting salient environmental changes and supports the idea that auditory inputs contribute directly to HC function.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145726765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/JNEUROSCI.0898-25.2025
Evan Weiss, Yuxiang Liu, Qi Wang
Understanding how pupil-linked arousal couples with cortical state is crucial for uncovering the neural mechanisms underlying brain state-dependent cognitive and sensory processing. Pupil size fluctuations reflect rapid changes of the pupil-linked arousal system, indexing brain states as well as the activity of neuromodulatory systems, including the locus ceruleus-norepinephrine (LC-NE) system. We investigated the relationship among phasic pupil dilation, cortical state, and neuromodulation by combining optogenetic LC stimulation with electroencephalogram (EEG) recordings and pupillometry in awake mice of both sexes. A comparison between EEG signals during spontaneous phasic pupil dilation and those during phasic pupil dilation evoked by LC stimulation revealed distinct cortical states. Using machine learning techniques, we trained a convolutional neural network classifier to distinguish between types of pupil dilation based on the power dynamics of individual EEG frequency bands. The results confirmed that all EEG bands, but most significantly gamma, differ markedly between spontaneous phasic arousal and LC stimulation-evoked arousal. Moreover, pharmacological manipulations to either block α- or β-adrenergic receptors or agonize α-2-adrenergic receptors were employed to explore how adrenergic receptors could influence the coupling between phasic pupil dilation and cortical state. With each manipulation uniquely modulating EEG power and pupil size, our results highlight the differentiated role of adrenergic receptors in moderating the coupling between pupil-linked arousal and cortical state. This study provides new insights into the complex relationship between pupil-linked arousal and cortical arousal state, underscoring the significant role of the LC-NE system in influencing these arousal states.
{"title":"The Contribution of the Locus Ceruleus-Norepinephrine System to the Coupling between Pupil-Linked Arousal and Cortical State.","authors":"Evan Weiss, Yuxiang Liu, Qi Wang","doi":"10.1523/JNEUROSCI.0898-25.2025","DOIUrl":"10.1523/JNEUROSCI.0898-25.2025","url":null,"abstract":"<p><p>Understanding how pupil-linked arousal couples with cortical state is crucial for uncovering the neural mechanisms underlying brain state-dependent cognitive and sensory processing. Pupil size fluctuations reflect rapid changes of the pupil-linked arousal system, indexing brain states as well as the activity of neuromodulatory systems, including the locus ceruleus-norepinephrine (LC-NE) system. We investigated the relationship among phasic pupil dilation, cortical state, and neuromodulation by combining optogenetic LC stimulation with electroencephalogram (EEG) recordings and pupillometry in awake mice of both sexes. A comparison between EEG signals during spontaneous phasic pupil dilation and those during phasic pupil dilation evoked by LC stimulation revealed distinct cortical states. Using machine learning techniques, we trained a convolutional neural network classifier to distinguish between types of pupil dilation based on the power dynamics of individual EEG frequency bands. The results confirmed that all EEG bands, but most significantly gamma, differ markedly between spontaneous phasic arousal and LC stimulation-evoked arousal. Moreover, pharmacological manipulations to either block α- or β-adrenergic receptors or agonize α-2-adrenergic receptors were employed to explore how adrenergic receptors could influence the coupling between phasic pupil dilation and cortical state. With each manipulation uniquely modulating EEG power and pupil size, our results highlight the differentiated role of adrenergic receptors in moderating the coupling between pupil-linked arousal and cortical state. This study provides new insights into the complex relationship between pupil-linked arousal and cortical arousal state, underscoring the significant role of the LC-NE system in influencing these arousal states.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828892/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145662070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/jneurosci.1636-25.2026
Melissa Malvaez,Andrea Suarez,Nicholas K Griffin,Kathia Ramírez-Armenta,Sean B Ostlund,Kate M Wassum
Reward predictions not only promote reward pursuit, they also shape how reward is pursed. Such predictions are supported by environmental cues that signal reward availability and probability. Such cues trigger dopamine release in the nucleus accumbens core (NAc). Thus, here we used dopamine sensor fiber photometry, cell-type and pathway-specific optogenetic inhibition, Pavlovian cue-reward conditioning, and test of cue-induced reward-pursuit strategy in male and female rats, to ask whether cue-evoked phasic dopamine release is shaped by reward prediction to support reward pursuit. We found that cue-evoked NAc core dopamine is positively shaped by reward prediction and inversely relates to and predicts instrumental reward seeking. Cues that predicted imminent reward with high probability triggered a large NAc dopamine response and this was associated checking for the expected reward in the delivery location, rather than instrumental reward seeking. Cues that predicted reward with low probability elicited less dopamine and this was associated with a bias towards seeking, rather than check for reward. Correspondingly, inhibition of cue-evoked NAc dopamine increased instrumental reward-seeking and decreased reward-checking behavior. Thus, transient, cue-evoked NAc core dopamine release supports reward prediction to shape reward-pursuit strategy.Significance statement Cues that signal reward availability promote reward pursuit. To ensure this is adaptive, we use the predictions these cues enable to select how to pursue reward. When reward prediction is low, we'll seek out new reward opportunities. When it is high, we'll check for the reward it in its usual location. Here we discovered that cue-evoked nucleus accumbens dopamine supports reward predictions to shape how reward is pursued. The data show that dopamine can actually constrain reward seeking and promote reward checking when reward is predicted strongly and imminently. These results provide new information on how dopamine shapes behavior in the moment and help understand the link between motivational and dopamine disruptions in psychiatric conditions such as addictions and depression.
{"title":"Dopamine supports reward prediction to shape reward-pursuit strategy.","authors":"Melissa Malvaez,Andrea Suarez,Nicholas K Griffin,Kathia Ramírez-Armenta,Sean B Ostlund,Kate M Wassum","doi":"10.1523/jneurosci.1636-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1636-25.2026","url":null,"abstract":"Reward predictions not only promote reward pursuit, they also shape how reward is pursed. Such predictions are supported by environmental cues that signal reward availability and probability. Such cues trigger dopamine release in the nucleus accumbens core (NAc). Thus, here we used dopamine sensor fiber photometry, cell-type and pathway-specific optogenetic inhibition, Pavlovian cue-reward conditioning, and test of cue-induced reward-pursuit strategy in male and female rats, to ask whether cue-evoked phasic dopamine release is shaped by reward prediction to support reward pursuit. We found that cue-evoked NAc core dopamine is positively shaped by reward prediction and inversely relates to and predicts instrumental reward seeking. Cues that predicted imminent reward with high probability triggered a large NAc dopamine response and this was associated checking for the expected reward in the delivery location, rather than instrumental reward seeking. Cues that predicted reward with low probability elicited less dopamine and this was associated with a bias towards seeking, rather than check for reward. Correspondingly, inhibition of cue-evoked NAc dopamine increased instrumental reward-seeking and decreased reward-checking behavior. Thus, transient, cue-evoked NAc core dopamine release supports reward prediction to shape reward-pursuit strategy.Significance statement Cues that signal reward availability promote reward pursuit. To ensure this is adaptive, we use the predictions these cues enable to select how to pursue reward. When reward prediction is low, we'll seek out new reward opportunities. When it is high, we'll check for the reward it in its usual location. Here we discovered that cue-evoked nucleus accumbens dopamine supports reward predictions to shape how reward is pursued. The data show that dopamine can actually constrain reward seeking and promote reward checking when reward is predicted strongly and imminently. These results provide new information on how dopamine shapes behavior in the moment and help understand the link between motivational and dopamine disruptions in psychiatric conditions such as addictions and depression.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"31 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/jneurosci.1743-25.2026
Jessica T Jacobs,Mikaela L Aholt,Taylor Lineberry,Magdalene P Adjei,Elana Qasem,Sophia Aaflaq,Sandria W Athul,Buffy S Ellsworth,Jacob C Nordman
Social novelty preference-the tendency to interact more with unfamiliar than familiar conspecifics-is conserved across species and disrupted in disorders such as autism spectrum disorder, schizophrenia, and social anxiety. While the hippocampus and related circuits are known to encode social recognition memory, the mechanisms that translate familiarity signals into behavioral differences remain unclear. Here, we show that male mice exhibit a robust preference for engaging with unfamiliar over familiar conspecifics. Using c-Fos labeling, RNAscope, immunohistochemistry, and fiber photometry, we found that inhibitory and DRD1-expressing neurons in the dorsal subdivision of the anterior bed nucleus of the stria terminalis (BNSTa) are broadly activated during social and novel-object interaction. However, chemogenetic inhibition of the BNSTa selectively suppressed interaction with unfamiliar conspecifics while leaving familiar and novel-object interactions unaffected. These findings identify the BNSTa as a critical node that promotes novelty-driven social engagement, revealing a circuit mechanism for social novelty preference. Because deficits in novelty processing are central to multiple neuropsychiatric disorders, our results highlight the BNST as a potential locus of dysfunction linking social recognition to behavior.Significance statement Recognizing whether a social partner is familiar or unfamiliar is fundamental for survival, yet most research has overlooked how familiarity shapes social behavior. Here we identify the anterior bed nucleus of the stria terminalis (BNSTa) as a critical regulator of interactions with unfamiliar conspecifics. Although BNSTa inhibitory neurons are broadly engaged during social encounters, chemogenetic inhibition selectively suppresses social engagement with strangers while leaving interactions with familiar conspecifics and objects intact. These findings reveal a previously unexplored role for the BNSTa in promoting novelty-driven social interaction. Because disruptions in social novelty processing are a hallmark of conditions such as autism spectrum disorder, schizophrenia, and social anxiety, our results provide insight into how BNST dysfunction may contribute to psychiatric social deficits.
{"title":"The anterior BNST is required for novelty-driven social interaction.","authors":"Jessica T Jacobs,Mikaela L Aholt,Taylor Lineberry,Magdalene P Adjei,Elana Qasem,Sophia Aaflaq,Sandria W Athul,Buffy S Ellsworth,Jacob C Nordman","doi":"10.1523/jneurosci.1743-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1743-25.2026","url":null,"abstract":"Social novelty preference-the tendency to interact more with unfamiliar than familiar conspecifics-is conserved across species and disrupted in disorders such as autism spectrum disorder, schizophrenia, and social anxiety. While the hippocampus and related circuits are known to encode social recognition memory, the mechanisms that translate familiarity signals into behavioral differences remain unclear. Here, we show that male mice exhibit a robust preference for engaging with unfamiliar over familiar conspecifics. Using c-Fos labeling, RNAscope, immunohistochemistry, and fiber photometry, we found that inhibitory and DRD1-expressing neurons in the dorsal subdivision of the anterior bed nucleus of the stria terminalis (BNSTa) are broadly activated during social and novel-object interaction. However, chemogenetic inhibition of the BNSTa selectively suppressed interaction with unfamiliar conspecifics while leaving familiar and novel-object interactions unaffected. These findings identify the BNSTa as a critical node that promotes novelty-driven social engagement, revealing a circuit mechanism for social novelty preference. Because deficits in novelty processing are central to multiple neuropsychiatric disorders, our results highlight the BNST as a potential locus of dysfunction linking social recognition to behavior.Significance statement Recognizing whether a social partner is familiar or unfamiliar is fundamental for survival, yet most research has overlooked how familiarity shapes social behavior. Here we identify the anterior bed nucleus of the stria terminalis (BNSTa) as a critical regulator of interactions with unfamiliar conspecifics. Although BNSTa inhibitory neurons are broadly engaged during social encounters, chemogenetic inhibition selectively suppresses social engagement with strangers while leaving interactions with familiar conspecifics and objects intact. These findings reveal a previously unexplored role for the BNSTa in promoting novelty-driven social interaction. Because disruptions in social novelty processing are a hallmark of conditions such as autism spectrum disorder, schizophrenia, and social anxiety, our results provide insight into how BNST dysfunction may contribute to psychiatric social deficits.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"142 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/JNEUROSCI.1221-25.2025
Esteban Bullón Tarrasó, Fabian Schwimmbeck, Marit Petzka, Tobias Staudigl, Bernhard P Staresina, Thomas Schreiner
Respiration has been shown to impact memory retrieval, yet the neural dynamics underlying this effect remain unclear. Here, we investigated how respiration shapes both behavioral and neural expressions of memory retrieval by reanalyzing an existing dataset where scalp electroencephalography and respiration recordings were acquired while participants (N = 18, 15 females) performed an episodic memory task. Our results unveil that respiration influences retrieval-related power fluctuations in the α/β band and concomitant memory reactivation. Specifically, we found that both key neural signatures of successful remembering were comodulated during exhalation, with the strength of the interaction between respiration and reactivation processes being associated with memory performance. Together, these findings suggest that respiration may act as a scaffold for episodic memory retrieval in humans by coordinating the neural conditions that support effective remembering.
{"title":"Respiration Shapes the Neural Dynamics of Successful Remembering in Humans.","authors":"Esteban Bullón Tarrasó, Fabian Schwimmbeck, Marit Petzka, Tobias Staudigl, Bernhard P Staresina, Thomas Schreiner","doi":"10.1523/JNEUROSCI.1221-25.2025","DOIUrl":"10.1523/JNEUROSCI.1221-25.2025","url":null,"abstract":"<p><p>Respiration has been shown to impact memory retrieval, yet the neural dynamics underlying this effect remain unclear. Here, we investigated how respiration shapes both behavioral and neural expressions of memory retrieval by reanalyzing an existing dataset where scalp electroencephalography and respiration recordings were acquired while participants (<i>N</i> = 18, 15 females) performed an episodic memory task. Our results unveil that respiration influences retrieval-related power fluctuations in the α/β band and concomitant memory reactivation. Specifically, we found that both key neural signatures of successful remembering were comodulated during exhalation, with the strength of the interaction between respiration and reactivation processes being associated with memory performance. Together, these findings suggest that respiration may act as a scaffold for episodic memory retrieval in humans by coordinating the neural conditions that support effective remembering.</p>","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12828881/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145670709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/jneurosci.0015-25.2026
Charlotte Seng,Bálint Tamás,Rashmit Kaur,Wenshu Luo,Csaba Földy
While circuit formation is generally thought to be absent in the adult brain, there is evidence that the adult brain retains a considerable capacity for neuronal wiring. Among other findings, molecular programming by basic helix-loop-helix (bHLH) proteins can reactivate axon growth in adult neurons, allowing the investigation of the mechanisms and potential of adult brain rewiring. Here, we analyzed proteomic and transcriptomic changes during Id2- (a bHLH transcriptional regulator) and Ascl4- (a bHLH transcription factor) induced feedback and feedforward wiring in the hippocampus of adult male and female mice. We find that Id2 and Ascl4 share a molecular cascade through the transcription factor Stat1 and co-regulate a set of proteins that may constitute a core program for adult wiring. Unexpectedly, we also identify shared molecular changes that do not originate directly from the programmed neurons, but from endothelial cells and microglia. Taken together, our results suggest that adult brain wiring is regulated by specific molecular programs and dynamic interactions between the wiring neurons and the circuit environment.Significance statement Contrary to conventional views, axonal wiring and circuit formation is not limited to the developing brain but can also occur in the adult brain. Although this area of research remains largely unexplored in the naive brain, technologies to rewire the adult brain have the potential to help overcome severe limitations imposed by brain disease, injury, or aging. In this study, we investigate the signatures of adult brain wiring induced by molecular cell programming using different factors and reveal common molecular changes to better understand the underlying biological mechanisms.
{"title":"Molecular signatures of Id2- and Ascl4-induced wiring of adult hippocampal neurons.","authors":"Charlotte Seng,Bálint Tamás,Rashmit Kaur,Wenshu Luo,Csaba Földy","doi":"10.1523/jneurosci.0015-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.0015-25.2026","url":null,"abstract":"While circuit formation is generally thought to be absent in the adult brain, there is evidence that the adult brain retains a considerable capacity for neuronal wiring. Among other findings, molecular programming by basic helix-loop-helix (bHLH) proteins can reactivate axon growth in adult neurons, allowing the investigation of the mechanisms and potential of adult brain rewiring. Here, we analyzed proteomic and transcriptomic changes during Id2- (a bHLH transcriptional regulator) and Ascl4- (a bHLH transcription factor) induced feedback and feedforward wiring in the hippocampus of adult male and female mice. We find that Id2 and Ascl4 share a molecular cascade through the transcription factor Stat1 and co-regulate a set of proteins that may constitute a core program for adult wiring. Unexpectedly, we also identify shared molecular changes that do not originate directly from the programmed neurons, but from endothelial cells and microglia. Taken together, our results suggest that adult brain wiring is regulated by specific molecular programs and dynamic interactions between the wiring neurons and the circuit environment.Significance statement Contrary to conventional views, axonal wiring and circuit formation is not limited to the developing brain but can also occur in the adult brain. Although this area of research remains largely unexplored in the naive brain, technologies to rewire the adult brain have the potential to help overcome severe limitations imposed by brain disease, injury, or aging. In this study, we investigate the signatures of adult brain wiring induced by molecular cell programming using different factors and reveal common molecular changes to better understand the underlying biological mechanisms.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"180 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015268","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-21DOI: 10.1523/jneurosci.1939-25.2026
Xuetong Li,Meng Xie,Carlos F Ibáñez
The p75 neurotrophin receptor (p75NTR) contributes to the development of Alzheimer's Disease (AD) pathology by enhancing amyloid precursor protein (APP) cleavage and amyloid plaque formation. However, the cell type-specific and temporal roles of p75NTR in AD progression remain unclear. Here, we report that conditional knock-in of functionally impaired p75NTR variants lacking the death domain (ΔDD) or transmembrane Cys259 (C259A) specifically in forebrain excitatory neurons of male and female 5xFAD mice significantly attenuated multiple AD-associated pathologies, including amyloid plaque accumulation, gliosis, neurite dystrophy, as well as learning and memory deficits. Hippocampal amyloid plaque burden was reduced to levels comparable to those found in whole-body knock-in mice. Strikingly, delaying introduction of p75NTR variants until advanced disease stages produced comparable beneficial effects, and rescued behavior performance in cognitively impaired animals. These findings suggest that blunting p75NTR function can have beneficial effects even during symptomatic stages of AD, offering a potential therapeutic approach complementary to passive vaccination.Significance Statement Inactivation of p75NTR has been reported to show various degrees of neuroprotection in Aβ-based mouse models of AD. As p75NTR is expressed in several different cell types in the brain, it has been unclear whether the beneficial effects afforded arose from all cell types or only one. For therapeutic approaches to be viable in AD patients, any form of interference with its activity needs to demonstrate beneficial effects during symptomatic stages of the disease. Here, we show that replacement of native p75NTR with signaling-impaired variants in forebrain excitatory neurons is sufficient to significantly alleviate neuropathological and behavioral outcomes in 5xFAD mice. Moreover, significant amelioration of neuropathology and cognitive deficits were achieved after acute disruption of p75NTR during symptomatic AD stages.
{"title":"Amelioration of symptomatic Alzheimer's Disease after selective impairment of p75NTR function in adult forebrain excitatory neurons.","authors":"Xuetong Li,Meng Xie,Carlos F Ibáñez","doi":"10.1523/jneurosci.1939-25.2026","DOIUrl":"https://doi.org/10.1523/jneurosci.1939-25.2026","url":null,"abstract":"The p75 neurotrophin receptor (p75NTR) contributes to the development of Alzheimer's Disease (AD) pathology by enhancing amyloid precursor protein (APP) cleavage and amyloid plaque formation. However, the cell type-specific and temporal roles of p75NTR in AD progression remain unclear. Here, we report that conditional knock-in of functionally impaired p75NTR variants lacking the death domain (ΔDD) or transmembrane Cys259 (C259A) specifically in forebrain excitatory neurons of male and female 5xFAD mice significantly attenuated multiple AD-associated pathologies, including amyloid plaque accumulation, gliosis, neurite dystrophy, as well as learning and memory deficits. Hippocampal amyloid plaque burden was reduced to levels comparable to those found in whole-body knock-in mice. Strikingly, delaying introduction of p75NTR variants until advanced disease stages produced comparable beneficial effects, and rescued behavior performance in cognitively impaired animals. These findings suggest that blunting p75NTR function can have beneficial effects even during symptomatic stages of AD, offering a potential therapeutic approach complementary to passive vaccination.Significance Statement Inactivation of p75NTR has been reported to show various degrees of neuroprotection in Aβ-based mouse models of AD. As p75NTR is expressed in several different cell types in the brain, it has been unclear whether the beneficial effects afforded arose from all cell types or only one. For therapeutic approaches to be viable in AD patients, any form of interference with its activity needs to demonstrate beneficial effects during symptomatic stages of the disease. Here, we show that replacement of native p75NTR with signaling-impaired variants in forebrain excitatory neurons is sufficient to significantly alleviate neuropathological and behavioral outcomes in 5xFAD mice. Moreover, significant amelioration of neuropathology and cognitive deficits were achieved after acute disruption of p75NTR during symptomatic AD stages.","PeriodicalId":50114,"journal":{"name":"Journal of Neuroscience","volume":"39 1","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146015310","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}