Pub Date : 2024-09-20Print Date: 2024-09-01DOI: 10.1523/ENEURO.0206-24.2024
Robert Botelho, Rex M Philpot
Chemotherapy-related cognitive impairments (CRCIs) encompass cognitive deficits in memory, attention, and executive function that arise during and following chemotherapy. CRCI symptoms are predominantly reported by female cancer patients but also occur in males. These impairments may involve reduced estradiol levels, which then increases vulnerability to the impact of tumors and chemotherapy on cognition. This study utilized the MMTV-PyVT mouse model of breast cancer to test the hypothesis that impaired ovarian function and associated estradiol levels play a critical role in CRCI susceptibility. Mice were either ovariectomized (OVX) or underwent sham surgery. The OVX group then received supplemental estradiol (E2) ad libitum in the drinking water to maintain physiological hormone levels. After tumor development, mice were trained in the Morris water maze to assess spatial memory, and subsequently, they received weekly injections of either saline or a combination of cyclophosphamide (CYP; 66.7 mg/kg, i.v.) and doxorubicin (DOX; 6.7 mg/kg, i.v.) for 4 weeks. Spatial memory was reassessed 10 d and then 35 d, after the final injections. Results demonstrated a significant disruption of normal ovarian cycling in sham-operated mice treated with CYP + DOX, as well as significant spatial memory impairments when compared with OVX mice supplemented with E2 This study suggests that chemotherapy-induced ovarian damage and the consequent drop in circulating estrogens significantly contribute to vulnerability to CRCIs, underscoring the importance of estradiol in mitigating CRCI risks.
{"title":"Ovariectomy and Estradiol Supplementation Prevents Cyclophosphamide- and Doxorubicin-Induced Spatial Memory Impairment in Tumor-Bearing MMTV-PyVT Mice.","authors":"Robert Botelho, Rex M Philpot","doi":"10.1523/ENEURO.0206-24.2024","DOIUrl":"10.1523/ENEURO.0206-24.2024","url":null,"abstract":"<p><p>Chemotherapy-related cognitive impairments (CRCIs) encompass cognitive deficits in memory, attention, and executive function that arise during and following chemotherapy. CRCI symptoms are predominantly reported by female cancer patients but also occur in males. These impairments may involve reduced estradiol levels, which then increases vulnerability to the impact of tumors and chemotherapy on cognition. This study utilized the MMTV-PyVT mouse model of breast cancer to test the hypothesis that impaired ovarian function and associated estradiol levels play a critical role in CRCI susceptibility. Mice were either ovariectomized (OVX) or underwent sham surgery. The OVX group then received supplemental estradiol (E<sup>2</sup>) <i>ad libitum</i> in the drinking water to maintain physiological hormone levels. After tumor development, mice were trained in the Morris water maze to assess spatial memory, and subsequently, they received weekly injections of either saline or a combination of cyclophosphamide (CYP; 66.7 mg/kg, i.v.) and doxorubicin (DOX; 6.7 mg/kg, i.v.) for 4 weeks. Spatial memory was reassessed 10 d and then 35 d, after the final injections. Results demonstrated a significant disruption of normal ovarian cycling in sham-operated mice treated with CYP + DOX, as well as significant spatial memory impairments when compared with OVX mice supplemented with E<sup>2</sup> This study suggests that chemotherapy-induced ovarian damage and the consequent drop in circulating estrogens significantly contribute to vulnerability to CRCIs, underscoring the importance of estradiol in mitigating CRCI risks.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419695/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20Print Date: 2024-09-01DOI: 10.1523/ENEURO.0266-24.2024
Michelle P Awh, Kenneth W Latimer, Nan Zhou, Zachary M Leveroni, Anna G Poon, Zoe M Stephens, Jai Y Yu
Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.
{"title":"Persistent Impact of Prior Experience on Spatial Learning.","authors":"Michelle P Awh, Kenneth W Latimer, Nan Zhou, Zachary M Leveroni, Anna G Poon, Zoe M Stephens, Jai Y Yu","doi":"10.1523/ENEURO.0266-24.2024","DOIUrl":"10.1523/ENEURO.0266-24.2024","url":null,"abstract":"<p><p>Learning to solve a new problem involves identifying the operating rules, which can be accelerated if known rules generalize in the new context. We ask how prior experience affects learning a new rule that is distinct from known rules. We examined how rats learned a new spatial navigation task after having previously learned tasks with different navigation rules. The new task differed from the previous tasks in spatial layout and navigation rule. We found that experience history did not impact overall performance. However, by examining navigation choice sequences in the new task, we found experience-dependent differences in exploration patterns during early stages of learning, as well as differences in the types of errors made during stable performance. The differences were consistent with the animals adopting experience-dependent memory strategies to discover and implement the new rule. Our results indicate prior experience shapes the strategies for solving novel problems, and the impact of prior experience remains persistent.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419697/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282200","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-20Print Date: 2024-09-01DOI: 10.1523/ENEURO.0365-24.2024
Braden N Maxwell, Afagh Farhadi, Marc A Brennan, Adam Svec, Laurel H Carney
Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.
以往的生理和心理物理研究探讨了传出系统对耳蜗的反馈是否会影响前向遮蔽。本研究提出,在听觉神经(AN)纤维中观察到的有限掩蔽增长(GOM)可能被误解了,即这种限制可能是由于麻醉对传出系统的影响。在未麻醉的听觉神经元可能表现出与更多中心核类似的 GOM 的前提下,本计算模型研究证明,来自内侧橄榄耳(MOC)传出的反馈可能有助于在耳蜗核和下丘(IC)的起始型神经元中观察到的生理性 GOM。此外,本文所使用的 MOC 传出因子计算模型会随着掩蔽器-信号延迟时间的延长而降低掩蔽程度,这与 IC 生理和心理物理研究中观察到的情况相似。与其他生理学解释(例如,前向掩蔽需要来自睑上核的抑制)相比,这一解释的优势在于,该理论可以解释在脑干、上升通路早期观察到的前向掩蔽。在解释心理声学结果方面,该模型的一个优点是它可以解释当掩蔽器水平在间隔与间隔之间随机变化时阈值不升高的现象,而这一结果是很难用心理物理前向掩蔽的传统时间窗模型来解释的。本文讨论了评估传出机制作为心理声学结果的促成机制的未来方向。 意义声明 本文的模拟证明,最近建立的听觉皮层下计算模型包括内侧-耳蜗传出,该模型可产生前向掩蔽,即在前一个声音之后,短探头音的检测阈值升高。该模型解释了生理记录的结果,并提出了与心理声学实验的潜在联系。耳蜗增益的传出控制是前向掩蔽的一个促成机制,这一理论解释了耳蜗核神经元表现出的掩蔽强度(生理学理论无法解释,在生理学理论中,前向掩蔽的强度是在上升通路的后期增加的),也解释了掩蔽水平随机变化的心理声学任务的结果(持续的掩蔽能量干扰探头检测的理论无法解释)。
{"title":"A Subcortical Model for Auditory Forward Masking with Efferent Control of Cochlear Gain.","authors":"Braden N Maxwell, Afagh Farhadi, Marc A Brennan, Adam Svec, Laurel H Carney","doi":"10.1523/ENEURO.0365-24.2024","DOIUrl":"10.1523/ENEURO.0365-24.2024","url":null,"abstract":"<p><p>Previous physiological and psychophysical studies have explored whether feedback to the cochlea from the efferent system influences forward masking. The present work proposes that the limited growth-of-masking (GOM) observed in auditory nerve (AN) fibers may have been misunderstood; namely, that this limitation may be due to the influence of anesthesia on the efferent system. Building on the premise that the unanesthetized AN may exhibit GOM similar to more central nuclei, the present computational modeling study demonstrates that feedback from the medial olivocochlear (MOC) efferents may contribute to GOM observed physiologically in onset-type neurons in both the cochlear nucleus and inferior colliculus (IC). Additionally, the computational model of MOC efferents used here generates a decrease in masking with longer masker-signal delays similar to that observed in IC physiology and in psychophysical studies. An advantage of this explanation over alternative physiological explanations (e.g., that forward masking requires inhibition from the superior paraolivary nucleus) is that this theory can explain forward masking observed in the brainstem, early in the ascending pathway. For explaining psychoacoustic results, one strength of this model is that it can account for the lack of elevation in thresholds observed when masker level is randomly varied from interval-to-interval, a result that is difficult to explain using the conventional temporal window model of psychophysical forward masking. Future directions for evaluating the efferent mechanism as a contributing mechanism for psychoacoustic results are discussed.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11419694/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the "bystander" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.
{"title":"Human NGF \"Painless\" Ocular Delivery for Retinitis Pigmentosa: An In Vivo Study.","authors":"Debora Napoli, Noemi Orsini, Giulia Salamone, Maria Antonietta Calvello, Simona Capsoni, Antonino Cattaneo, Enrica Strettoi","doi":"10.1523/ENEURO.0096-24.2024","DOIUrl":"https://doi.org/10.1523/ENEURO.0096-24.2024","url":null,"abstract":"<p><p>Retinitis pigmentosa (RP) is a family of genetically heterogeneous diseases still without a cure. Despite the causative genetic mutation typically not expressed in cone photoreceptors, these cells inevitably degenerate following the primary death of rods, causing blindness. The reasons for the \"bystander\" degeneration of cones are presently unknown but decrement of survival factors, oxidative stress, and inflammation all play a role. Targeting these generalized biological processes represents a strategy to develop mutation-agnostic therapies for saving vision in large populations of RP individuals. A classical method to support neuronal survival is by employing neurotrophic factors, such as NGF. This study uses painless human NGF (hNGFp), a TrkA receptor-biased variant of the native molecule with lower affinity for nociceptors and limited activity as a pain inducer; the molecule has identical neurotrophic power of the native form but a reduced affinity for the p75NTR receptors, known to trigger apoptosis. hNGFp has a recognized activity on brain microglial cells, which are induced to a phenotype switch from a highly activated to a more homeostatic configuration. hNGFp was administered to RP-like mice in vivo with the aim of decreasing retinal inflammation and also providing retinal neuroprotection. However, the ability of this treatment to counteract the bystander degeneration of cones remained limited.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-18Print Date: 2024-09-01DOI: 10.1523/ENEURO.0058-24.2024
Manal S Abdelaal, Tomonobu Kato, Akiyo Natsubori, Kenji F Tanaka
Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico-thalamo-cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited Pvalb-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.
{"title":"Temporal and Potential Predictive Relationships between Sleep Spindle Density and Spike-and-Wave Discharges.","authors":"Manal S Abdelaal, Tomonobu Kato, Akiyo Natsubori, Kenji F Tanaka","doi":"10.1523/ENEURO.0058-24.2024","DOIUrl":"https://doi.org/10.1523/ENEURO.0058-24.2024","url":null,"abstract":"<p><p>Spike-and-wave discharges (SWDs) and sleep spindles are characteristic electroencephalographic (EEG) hallmarks of absence seizures and nonrapid eye movement sleep, respectively. They are commonly generated by the cortico-thalamo-cortical network including the thalamic reticular nucleus (TRN). It has been reported that SWD development is accompanied by a decrease in sleep spindle density in absence seizure patients and animal models. However, whether the decrease in sleep spindle density precedes, coincides with, or follows, the SWD development remains unknown. To clarify this, we exploited <i>Pvalb</i>-tetracycline transactivator (tTA)::tetO-ArchT (PV-ArchT) double-transgenic mouse, which can induce an absence seizure phenotype in a time-controllable manner by expressing ArchT in PV neurons of the TRN. In these mice, EEG recordings demonstrated that a decrease in sleep spindle density occurred 1 week before the onset of typical SWDs, with the expression of ArchT. To confirm such temporal relationship observed in these genetic model mice, we used a gamma-butyrolactone (GBL) pharmacological model of SWDs. Prior to GBL administration, we administered caffeine to wild-type mice for 3 consecutive days to induce a decrease in sleep spindle density. We then administered low-dose GBL, which cannot induce SWDs in normally conditioned mice but led to the occurrence of SWDs in caffeine-conditioned mice. These findings indicate a temporal relationship in which the decrease in sleep spindle density consistently precedes SWD development. Furthermore, the decrease in sleep spindle activity may have a role in facilitating the development of SWDs. Our findings suggest that sleep spindle reductions could serve as early indicators of seizure susceptibility.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-16Print Date: 2024-09-01DOI: 10.1523/ENEURO.0013-24.2024
Keri Gladhill, Rose De Kock, Weiwei Zhou, Wilsaan Joiner, Martin Wiener
Contemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates. However, a critical test of this framework is that by introducing "noise" into movements, sensory estimates of time should similarly become noisier. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities (n = 24, ea.). Crucially, we introduced an artificial "tremor" in the arm while subjects were moving, that varied across three levels of amplitude (1-3 N) or frequency (4-12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration. Further, the effect of noise varied with the base precision of the interval, such that a naturally less precise timing (i.e., visual) was more influenced by the tremor than a naturally more precise modality (i.e., auditory). To explain these findings, we fit the data with a recently developed drift-diffusion model of perceptual decision-making, in which the momentary, within-trial variance was allowed to vary across conditions. Here, we found that the model could recapitulate the observed findings, further supporting the theory that movements influence perception directly. Overall, our findings support the proposed framework, and demonstrate the utility of inducing motor noise via artificial tremors.
{"title":"Mechanically Induced Motor Tremors Disrupt the Perception of Time.","authors":"Keri Gladhill, Rose De Kock, Weiwei Zhou, Wilsaan Joiner, Martin Wiener","doi":"10.1523/ENEURO.0013-24.2024","DOIUrl":"10.1523/ENEURO.0013-24.2024","url":null,"abstract":"<p><p>Contemporary research has begun to show a strong relationship between movements and the perception of time. More specifically, concurrent movements serve to both bias and enhance time estimates. To explain these effects, we recently proposed a mechanism by which movements provide a secondary channel for estimating duration that is combined optimally with sensory estimates. However, a critical test of this framework is that by introducing \"noise\" into movements, sensory estimates of time should similarly become noisier. To accomplish this, we had human participants move a robotic arm while estimating intervals of time in either auditory or visual modalities (<i>n</i> = 24, ea.). Crucially, we introduced an artificial \"tremor\" in the arm while subjects were moving, that varied across three levels of amplitude (1-3 N) or frequency (4-12 Hz). The results of both experiments revealed that increasing the frequency of the tremor led to noisier estimates of duration. Further, the effect of noise varied with the base precision of the interval, such that a naturally less precise timing (i.e., visual) was more influenced by the tremor than a naturally more precise modality (i.e., auditory). To explain these findings, we fit the data with a recently developed drift-diffusion model of perceptual decision-making, in which the momentary, within-trial variance was allowed to vary across conditions. Here, we found that the model could recapitulate the observed findings, further supporting the theory that movements influence perception directly. Overall, our findings support the proposed framework, and demonstrate the utility of inducing motor noise via artificial tremors.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11412164/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13Print Date: 2024-09-01DOI: 10.1523/ENEURO.0360-24.2024
{"title":"Erratum: Bruentgens et al., \"The Lack of Synapsin Alters Presynaptic Plasticity at Hippocampal Mossy Fibers in Male Mice\".","authors":"","doi":"10.1523/ENEURO.0360-24.2024","DOIUrl":"https://doi.org/10.1523/ENEURO.0360-24.2024","url":null,"abstract":"","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142282197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13Print Date: 2024-09-01DOI: 10.1523/ENEURO.0257-24.2024
Preston C Withers, Hunter J Morrill, R Ryley Parrish
Much of what has been discovered concerning neurophysiological mechanisms can be credited to ex vivo biomedical experiments. Beyond these discoveries, ex vivo research techniques have enhanced the global understanding of human physiology and pathology in almost every biomedical specialty. Naturally, ex vivo experiments are among the most desired methods of research, particularly in the field of neuroscience. Ex vivo experiment platforms may be purchased commercially. However, their substantial cost and sometimes limited availability can render them inaccessible to many research labs. Moreover, these manufactured systems are often rigid in function with no possibility of customization, severely narrowing their capabilities. However, developing essential components for ex vivo laboratory systems with a fused deposition modeling printer provides a practical solution to each of these obstacles. Here, we provide the designs and construction process for an easily accessible, highly adaptable recording stage with modifiable submersion chambers using a 3D printer for a total cost under $15.00. With the versatility afforded by the exchangeable custom chambers, the system may be used to conduct research on a variety of ex vivo tissue preparations, paving the way for novel research.
{"title":"An Open-Source 3D-Printed Recording Stage with Customizable Chambers for Ex Vivo Experiments.","authors":"Preston C Withers, Hunter J Morrill, R Ryley Parrish","doi":"10.1523/ENEURO.0257-24.2024","DOIUrl":"10.1523/ENEURO.0257-24.2024","url":null,"abstract":"<p><p>Much of what has been discovered concerning neurophysiological mechanisms can be credited to ex vivo biomedical experiments. Beyond these discoveries, ex vivo research techniques have enhanced the global understanding of human physiology and pathology in almost every biomedical specialty. Naturally, ex vivo experiments are among the most desired methods of research, particularly in the field of neuroscience. Ex vivo experiment platforms may be purchased commercially. However, their substantial cost and sometimes limited availability can render them inaccessible to many research labs. Moreover, these manufactured systems are often rigid in function with no possibility of customization, severely narrowing their capabilities. However, developing essential components for ex vivo laboratory systems with a fused deposition modeling printer provides a practical solution to each of these obstacles. Here, we provide the designs and construction process for an easily accessible, highly adaptable recording stage with modifiable submersion chambers using a 3D printer for a total cost under $15.00. With the versatility afforded by the exchangeable custom chambers, the system may be used to conduct research on a variety of ex vivo tissue preparations, paving the way for novel research.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-13Print Date: 2024-09-01DOI: 10.1523/ENEURO.0148-24.2024
Bas Lendemeijer, Maurits Unkel, Hilde Smeenk, Britt Mossink, Sara Hijazi, Sara Gordillo-Sampedro, Guy Shpak, Denise E Slump, Mirjam C G N van den Hout, Wilfred F J van IJcken, Eric M J Bindels, Witte J G Hoogendijk, Nael Nadif Kasri, Femke M S de Vrij, Steven A Kushner
Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± 0.44 min-1 (hPSC-derived), 2.86 ± 0.64 min-1 (rat); p = 0.19]. In comparison, we found increased spike frequency within network bursts of human neurons cocultured with hPSC-derived astrocytes [56.31 ± 8.56 Hz (hPSC-derived), 24.77 ± 4.04 Hz (rat); p < 0.01], and whole-cell patch-clamp recordings revealed an increase of postsynaptic currents [2.76 ± 0.39 Hz (hPSC-derived), 1.07 ± 0.14 Hz (rat); p < 0.001], consistent with a corresponding increase in synapse density [14.90 ± 1.27/100 μm2 (hPSC-derived), 8.39 ± 0.63/100 μm2 (rat); p < 0.001]. Taken together, we show that hPSC-derived astrocytes compare favorably with rat astrocytes in supporting human neural network activity and maturation, providing a fully human platform for investigating astrocyte function and neuronal-glial interactions.
{"title":"Human Pluripotent Stem Cell-Derived Astrocyte Functionality Compares Favorably with Primary Rat Astrocytes.","authors":"Bas Lendemeijer, Maurits Unkel, Hilde Smeenk, Britt Mossink, Sara Hijazi, Sara Gordillo-Sampedro, Guy Shpak, Denise E Slump, Mirjam C G N van den Hout, Wilfred F J van IJcken, Eric M J Bindels, Witte J G Hoogendijk, Nael Nadif Kasri, Femke M S de Vrij, Steven A Kushner","doi":"10.1523/ENEURO.0148-24.2024","DOIUrl":"10.1523/ENEURO.0148-24.2024","url":null,"abstract":"<p><p>Astrocytes are essential for the formation and maintenance of neural networks. However, a major technical challenge for investigating astrocyte function and disease-related pathophysiology has been the limited ability to obtain functional human astrocytes. Despite recent advances in human pluripotent stem cell (hPSC) techniques, primary rodent astrocytes remain the gold standard in coculture with human neurons. We demonstrate that a combination of leukemia inhibitory factor (LIF) and bone morphogenetic protein-4 (BMP4) directs hPSC-derived neural precursor cells to a highly pure population of astroglia in 28 d. Using single-cell RNA sequencing, we confirm the astroglial identity of these cells and highlight profound transcriptional adaptations in cocultured hPSC-derived astrocytes and neurons, consistent with their further maturation. In coculture with human neurons, multielectrode array recordings revealed robust network activity of human neurons in a coculture with hPSC-derived or rat astrocytes [3.63 ± 0.44 min<sup>-1</sup> (hPSC-derived), 2.86 ± 0.64 min<sup>-1</sup> (rat); <i>p </i>= 0.19]. In comparison, we found increased spike frequency within network bursts of human neurons cocultured with hPSC-derived astrocytes [56.31 ± 8.56 Hz (hPSC-derived), 24.77 ± 4.04 Hz (rat); <i>p </i>< 0.01], and whole-cell patch-clamp recordings revealed an increase of postsynaptic currents [2.76 ± 0.39 Hz (hPSC-derived), 1.07 ± 0.14 Hz (rat); <i>p </i>< 0.001], consistent with a corresponding increase in synapse density [14.90 ± 1.27/100 μm<sup>2</sup> (hPSC-derived), 8.39 ± 0.63/100 μm<sup>2</sup> (rat); <i>p </i>< 0.001]. Taken together, we show that hPSC-derived astrocytes compare favorably with rat astrocytes in supporting human neural network activity and maturation, providing a fully human platform for investigating astrocyte function and neuronal-glial interactions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11404293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142125160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Contrast sensitivity (CS), which constrains human vision, decreases from fovea to periphery, from the horizontal to the vertical meridian, and from the lower vertical to the upper vertical meridian. It also depends on spatial frequency (SF), and the contrast sensitivity function (CSF) depicts this relation. To compensate for these visual constraints, we constantly make saccades and foveate on relevant objects in the scene. Already before saccade onset, presaccadic attention shifts to the saccade target and enhances perception. However, it is unknown whether and how it modulates the interplay between CS and SF, and if this effect varies around polar angle meridians. CS enhancement may result from a horizontal or vertical shift of the CSF, increase in bandwidth, or any combination. In addition, presaccadic attention could enhance CS similarly around the visual field, or it could benefit perception more at locations with poorer performance (i.e., vertical meridian). Here, we investigated these possibilities by extracting key attributes of the CSF of human observers. The results reveal that presaccadic attention (1) increases CS across SF, (2) increases the most preferred and the highest discernable SF, and (3) narrows the bandwidth. Therefore, presaccadic attention helps bridge the gap between presaccadic and postsaccadic input by increasing visibility at the saccade target. Counterintuitively, this CS enhancement was more pronounced where perception is better-along the horizontal than the vertical meridian-exacerbating polar angle asymmetries. Our results call for an investigation of the differential neural modulations underlying presaccadic perceptual changes for different saccade directions.
对比敏感度制约着人类的视觉,从眼窝到周边,从水平经线到垂直经线,以及从垂直下经线到垂直上经线,对比敏感度都在下降。对比敏感度函数(CSF)描述了对比敏感度如何取决于空间频率(SF)。为了弥补这些视觉上的限制,我们会不断地进行眼球移动,以聚焦于场景中的相关物体。在囊回开始之前,前囊回注意力就已经转移到囊回目标上,从而增强了感知。然而,人们还不知道它是否以及如何调节对比敏感度和 SF 之间的相互作用,也不知道这种效应是否会随着极角位置的变化而变化。对比敏感度的增强可能是 CSF 水平或垂直移动、带宽增加或任何组合的结果。此外,累积前注意也可能在视野周围同样增强对比敏感度,或者在表现较差的位置(即垂直子午线)更有利于感知。在这里,我们通过提取人类观察者 CSF 的关键属性来研究这些可能性。研究结果表明,前积聚注意(1)增加了各SF的对比敏感度;(2)增加了最偏好和可辨别度最高的SF;(3)缩小了带宽。因此,前摄动注意通过增加囊状目标的能见度,有助于弥合前摄动和后摄动输入之间的差距。与直觉相反的是,在水平经线比垂直经线感知更好的地方,对比敏感度的前摄动增强更为明显,从而加剧了极角不对称。我们的研究结果要求对不同囊回方向的囊回前知觉变化背后的不同神经调制进行研究。 意义说明 对比敏感度函数(CSF)描述了我们感知对比的能力如何取决于空间频率。对比敏感度在眼窝处最高,而在外围则会降低,尤其是在沿垂直子午线的位置。因此,我们会通过眼球移动来观察物体的细节。在我们移动眼睛之前,预视注意就已经增强了对目标位置的感知。但是,它如何影响对比敏感度和空间频率之间的相互作用?通过使用层次贝叶斯建模,我们发现前注视会增强和重塑 CSF,使外围为即将到来的固定做好准备。有趣的是,在视力较强的水平位置,前积聚注意的作用更大,这表明水平方向的眼球运动比垂直方向的眼球运动更平滑。
{"title":"Presaccadic Attention Enhances and Reshapes the Contrast Sensitivity Function Differentially around the Visual Field.","authors":"Yuna Kwak, Yukai Zhao, Zhong-Lin Lu, Nina Maria Hanning, Marisa Carrasco","doi":"10.1523/ENEURO.0243-24.2024","DOIUrl":"10.1523/ENEURO.0243-24.2024","url":null,"abstract":"<p><p>Contrast sensitivity (CS), which constrains human vision, decreases from fovea to periphery, from the horizontal to the vertical meridian, and from the lower vertical to the upper vertical meridian. It also depends on spatial frequency (SF), and the contrast sensitivity function (CSF) depicts this relation. To compensate for these visual constraints, we constantly make saccades and foveate on relevant objects in the scene. Already before saccade onset, presaccadic attention shifts to the saccade target and enhances perception. However, it is unknown whether and how it modulates the interplay between CS and SF, and if this effect varies around polar angle meridians. CS enhancement may result from a horizontal or vertical shift of the CSF, increase in bandwidth, or any combination. In addition, presaccadic attention could enhance CS similarly around the visual field, or it could benefit perception more at locations with poorer performance (i.e., vertical meridian). Here, we investigated these possibilities by extracting key attributes of the CSF of human observers. The results reveal that presaccadic attention (1) increases CS across SF, (2) increases the most preferred and the highest discernable SF, and (3) narrows the bandwidth. Therefore, presaccadic attention helps bridge the gap between presaccadic and postsaccadic input by increasing visibility at the saccade target. Counterintuitively, this CS enhancement was more pronounced where perception is better-along the horizontal than the vertical meridian-exacerbating polar angle asymmetries. Our results call for an investigation of the differential neural modulations underlying presaccadic perceptual changes for different saccade directions.</p>","PeriodicalId":11617,"journal":{"name":"eNeuro","volume":null,"pages":null},"PeriodicalIF":2.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11397507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142092508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}