Pub Date : 2025-02-21DOI: 10.1016/j.pneurobio.2025.102730
Yu Zhang , Jianfei Long , Jian Xu , Ping Zhong , Bin Wang
Vestibular schwannoma (VS), characterized by the absence of merlin expression, is the most prevalent benign tumor located at the cerebellopontine angle, lacking approved pharmaceutical interventions except for off-label utilization of bevacizumab. The role of Tumor stiffness-Focal adhesion kinase (FAK) activation in fueling tumor progression is well-established, with merlin deficiency serving as a biomarker for tumor sensitivity to FAK inhibitors. In this context, we investigated whether Tumor stiffness-FAK contributes to VS progression. Single-cell RNA sequencing revealed associations between VS progression and gene sets related to “Response to mechanical stimulus” and “Neurotrophin signaling pathway”. Histological studies indicated a potential involvement of neurotrophins in early stages of VS tumorigenesis, while enhanced Extracellular matrix (ECM) remodeling-Tumor stiffness-FAK signaling accompanies later stages of VS progression. In vitro experiments demonstrated that elevated matrix stiffness induces cytoskeletal remodeling, cell proliferation, and metalloproteinase expression in VS cells by activating FAK. Conversely, FAK inhibition diminishes these effects. Collectively, this study suggests that ECM remodeling-Tumor stiffness contributes to VS progression via FAK activation, positioning FAK as a promising therapeutic target in treating VS.
{"title":"Single-cell RNA sequencing reveals ECM remodeling-tumor stiffness-FAK as a key driver of vestibular schwannoma progression","authors":"Yu Zhang , Jianfei Long , Jian Xu , Ping Zhong , Bin Wang","doi":"10.1016/j.pneurobio.2025.102730","DOIUrl":"10.1016/j.pneurobio.2025.102730","url":null,"abstract":"<div><div>Vestibular schwannoma (VS), characterized by the absence of merlin expression, is the most prevalent benign tumor located at the cerebellopontine angle, lacking approved pharmaceutical interventions except for off-label utilization of bevacizumab. The role of Tumor stiffness-Focal adhesion kinase (FAK) activation in fueling tumor progression is well-established, with merlin deficiency serving as a biomarker for tumor sensitivity to FAK inhibitors. In this context, we investigated whether Tumor stiffness-FAK contributes to VS progression. Single-cell RNA sequencing revealed associations between VS progression and gene sets related to “Response to mechanical stimulus” and “Neurotrophin signaling pathway”. Histological studies indicated a potential involvement of neurotrophins in early stages of VS tumorigenesis, while enhanced Extracellular matrix (ECM) remodeling-Tumor stiffness-FAK signaling accompanies later stages of VS progression. <em>In vitro</em> experiments demonstrated that elevated matrix stiffness induces cytoskeletal remodeling, cell proliferation, and metalloproteinase expression in VS cells by activating FAK. Conversely, FAK inhibition diminishes these effects. Collectively, this study suggests that ECM remodeling-Tumor stiffness contributes to VS progression via FAK activation, positioning FAK as a promising therapeutic target in treating VS.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102730"},"PeriodicalIF":6.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143479472","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 : 2025-02-20DOI: 10.1016/j.pneurobio.2025.102731
Andrea Alcaide Martin , Reinhard Bauer , Dagmar Führer-Sakel , Heike Heuer , Steffen Mayerl
Thyroid hormone (TH) transporters such as the monocarboxylate transporter Mct8 and the organic anion transporting protein Oatp1c1 facilitate TH transport into target cells. In humans, inactivating mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), a severe psychomotor retardation with hallmarks of a central TH deficit and frequently observed seizures of unknown etiology. Here, we aimed to investigate seizure susceptibility in AHDS by using Mct8/Oatp1c1 double-knockout (Dko) mice, a well-established AHDS model. We tested seizure susceptibility using the pilocarpine model and observed a significantly faster occurrence of status epilepticus (SE) and more severe responses to seizure induction in Dko animals. We analyzed neuronal alterations in the hippocampus, an area central in seizure pathology, 12 h after SE by immuno-fluorescence and in situ hybridization (ISH). Dko mice presented increased cFos immunoreactivity, and ectopic expression of somatostatin in CA3 neurons. To unravel underlying mechanisms, we studied neurotransmitter systems in murine hippocampi during development at P12 and in adulthood. Employing immuno-fluorescence, ISH and qPCR analyses, we revealed an abnormal development of the inhibitory GABAergic, excitatory glutamatergic and cholinergic systems in Dko mice. Together, our data point to an altered inhibition/excitation balance in the Dko hippocampus that may explain the increased seizure susceptibility.
{"title":"Increased seizure susceptibility in thyroid hormone transporter Mct8/Oatp1c1 knockout mice is associated with altered neurotransmitter systems development","authors":"Andrea Alcaide Martin , Reinhard Bauer , Dagmar Führer-Sakel , Heike Heuer , Steffen Mayerl","doi":"10.1016/j.pneurobio.2025.102731","DOIUrl":"10.1016/j.pneurobio.2025.102731","url":null,"abstract":"<div><div>Thyroid hormone (TH) transporters such as the monocarboxylate transporter Mct8 and the organic anion transporting protein Oatp1c1 facilitate TH transport into target cells. In humans, inactivating mutations in MCT8 result in Allan-Herndon-Dudley syndrome (AHDS), a severe psychomotor retardation with hallmarks of a central TH deficit and frequently observed seizures of unknown etiology. Here, we aimed to investigate seizure susceptibility in AHDS by using Mct8/Oatp1c1 double-knockout (Dko) mice, a well-established AHDS model. We tested seizure susceptibility using the pilocarpine model and observed a significantly faster occurrence of status epilepticus (SE) and more severe responses to seizure induction in Dko animals. We analyzed neuronal alterations in the hippocampus, an area central in seizure pathology, 12 h after SE by immuno-fluorescence and in situ hybridization (ISH). Dko mice presented increased cFos immunoreactivity, and ectopic expression of somatostatin in CA3 neurons. To unravel underlying mechanisms, we studied neurotransmitter systems in murine hippocampi during development at P12 and in adulthood. Employing immuno-fluorescence, ISH and qPCR analyses, we revealed an abnormal development of the inhibitory GABAergic, excitatory glutamatergic and cholinergic systems in Dko mice. Together, our data point to an altered inhibition/excitation balance in the Dko hippocampus that may explain the increased seizure susceptibility.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"247 ","pages":"Article 102731"},"PeriodicalIF":6.7,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143477095","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 : 2025-02-15DOI: 10.1016/j.pneurobio.2025.102728
Noémie Depret , Marie Gleizes , Maïté Marie Moreau , Sonia Poirault-Chassac , Anne Quiedeville , Steve Dos Santos Carvalho , Vasika Venugopal , Alice Shaam Al Abed , Jérôme Ezan , Gael Barthet , Christophe Mulle , Aline Desmedt , Aline Marighetto , Claudia Racca , Mireille Montcouquiol , Nathalie Sans
In the hippocampus, dentate gyrus granule cells connect to CA3 pyramidal cells via their axons, the mossy fibers (Mf). The synaptic terminals of Mfs (Mf boutons, MfBs) form large and complex synapses with thorny excrescences (TE) on the proximal dendrites of CA3 pyramidal cells (PCs). MfB/TE synapses have distinctive “detonator” properties due to low initial release probability and large presynaptic facilitation. The molecular mechanisms shaping the morpho-functional properties of MfB/TE synapses are still poorly understood, though alterations in their morphology are associated with Down syndrome, intellectual disabilities, and Alzheimer’s disease. Here, we identify the core PCP gene Vangl2 as essential to the morphogenesis and function of MfB/TE synapses. Vangl2 colocalises with the presynaptic heparan sulfate proteoglycan glypican 4 (GPC4) to stabilise the postsynaptic orphan receptor GPR158. Embryonic loss of Vangl2 disrupts the morphology of MfBs and TEs, impairs ultrastructural and molecular organisation, resulting in defective synaptic transmission and plasticity. In adult, the early loss of Vangl2 results in a number of hippocampus-dependent memory deficits including characteristic flexibility of declarative memory, organisation and retention of working / everyday-like memory. These deficits also lead to abnormal generalisation of memories to salient cues and diminished ability to form detailed contextual memories. Together, these results establish Vangl2 as a key regulator of DG-CA3 connectivity and functions.
{"title":"The correct connectivity of the DG-CA3 circuits involved in declarative memory processes depends on Vangl2-dependent planar cell polarity signaling","authors":"Noémie Depret , Marie Gleizes , Maïté Marie Moreau , Sonia Poirault-Chassac , Anne Quiedeville , Steve Dos Santos Carvalho , Vasika Venugopal , Alice Shaam Al Abed , Jérôme Ezan , Gael Barthet , Christophe Mulle , Aline Desmedt , Aline Marighetto , Claudia Racca , Mireille Montcouquiol , Nathalie Sans","doi":"10.1016/j.pneurobio.2025.102728","DOIUrl":"10.1016/j.pneurobio.2025.102728","url":null,"abstract":"<div><div>In the hippocampus, dentate gyrus granule cells connect to CA3 pyramidal cells via their axons, the mossy fibers (Mf). The synaptic terminals of Mfs (Mf boutons, MfBs) form large and complex synapses with thorny excrescences (TE) on the proximal dendrites of CA3 pyramidal cells (PCs). MfB/TE synapses have distinctive “detonator” properties due to low initial release probability and large presynaptic facilitation. The molecular mechanisms shaping the morpho-functional properties of MfB/TE synapses are still poorly understood, though alterations in their morphology are associated with Down syndrome, intellectual disabilities, and Alzheimer’s disease. Here, we identify the core PCP gene <em>Vangl2</em> as essential to the morphogenesis and function of MfB/TE synapses. Vangl2 colocalises with the presynaptic heparan sulfate proteoglycan glypican 4 (GPC4) to stabilise the postsynaptic orphan receptor GPR158. Embryonic loss of Vangl2 disrupts the morphology of MfBs and TEs, impairs ultrastructural and molecular organisation, resulting in defective synaptic transmission and plasticity. In adult, the early loss of Vangl2 results in a number of hippocampus-dependent memory deficits including characteristic flexibility of declarative memory, organisation and retention of working / everyday-like memory. These deficits also lead to abnormal generalisation of memories to salient cues and diminished ability to form detailed contextual memories. Together, these results establish Vangl2 as a key regulator of DG-CA3 connectivity and functions.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"246 ","pages":"Article 102728"},"PeriodicalIF":6.7,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143433567","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 : 2025-02-01DOI: 10.1016/j.pneurobio.2024.102704
Ling Zhao , Menno P. Witter , Nicola Palomero-Gallagher
Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative in vivo receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes. We provide a novel and comprehensive characterization of the cyto-, gene, and multireceptor architecture of the developing mouse hippocampal and subicular regions during the developmental period, which typically differs from that in the adult brain. High-density receptor expressions with distinct regional and laminar distributions were observed for AMPA, Kainate, mGluR2/3, GABAA, GABAA/BZ, α2, and A1 receptors during this specific period, whereas NMDA, GABAB, α1, M1, M2, M3, nicotinic α4β2, 5-HT1A, 5-HT2, D1 and D2/D3 receptors exhibited relatively low and homogeneous expressions. This specific balance of multiple receptors aligns with regional cytoarchitecture, neurotransmitter distributions, and gene expressions. Moreover, contrasting with previous findings, we detected a high α2 receptor density, with distinct regional and laminar distribution patterns. A non-covariation differentiation phenomenon between α2 receptor distributions and corresponding gene expressions is also demonstrated in this early developmental period. The multimodal data provides new insights into understanding the hippocampal development from the perspective of cell, gene, and multireceptor levels, and contributes important resources for further interdisciplinary analyses.
{"title":"Cyto-, gene, and multireceptor architecture of the early postnatal mouse hippocampal complex","authors":"Ling Zhao , Menno P. Witter , Nicola Palomero-Gallagher","doi":"10.1016/j.pneurobio.2024.102704","DOIUrl":"10.1016/j.pneurobio.2024.102704","url":null,"abstract":"<div><div>Neurotransmitter receptors are key molecules in signal transmission in the adult brain, and their precise spatial and temporal balance expressions also play a critical role in normal brain development. However, the specific balance expression of multiple receptors during hippocampal development is not well characterized. In this study, we used quantitative <em>in vivo</em> receptor autoradiography to measure the distributions and densities of 18 neurotransmitter receptor types in the mouse hippocampal complex at postnatal day 7, and compared them with the expressions of their corresponding encoding genes. We provide a novel and comprehensive characterization of the cyto-, gene, and multireceptor architecture of the developing mouse hippocampal and subicular regions during the developmental period, which typically differs from that in the adult brain. High-density receptor expressions with distinct regional and laminar distributions were observed for AMPA, Kainate, mGluR2/3, GABA<sub>A</sub>, GABA<sub>A</sub>/BZ, α<sub>2</sub>, and A<sub>1</sub> receptors during this specific period, whereas NMDA, GABA<sub>B</sub>, α<sub>1</sub>, M<sub>1</sub>, M<sub>2</sub>, M<sub>3</sub>, nicotinic α<sub>4</sub>β<sub>2</sub>, 5-HT<sub>1A</sub>, 5-HT<sub>2</sub>, D<sub>1</sub> and D<sub>2</sub>/D<sub>3</sub> receptors exhibited relatively low and homogeneous expressions. This specific balance of multiple receptors aligns with regional cytoarchitecture, neurotransmitter distributions, and gene expressions. Moreover, contrasting with previous findings, we detected a high α<sub>2</sub> receptor density, with distinct regional and laminar distribution patterns. A non-covariation differentiation phenomenon between α<sub>2</sub> receptor distributions and corresponding gene expressions is also demonstrated in this early developmental period. The multimodal data provides new insights into understanding the hippocampal development from the perspective of cell, gene, and multireceptor levels, and contributes important resources for further interdisciplinary analyses.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102704"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872814","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 : 2025-02-01DOI: 10.1016/j.pneurobio.2024.102708
Emma Robson , Margaret M. Donahue , Alexandra J. Mably , Peyton G. Demetrovich , Lauren T. Hewitt , Laura Lee Colgin
Hippocampal region CA2 is essential for social memory processing. Interaction with social stimuli induces changes in CA2 place cell firing during active exploration and sharp wave-ripples during rest following a social interaction. However, it is unknown whether these changes in firing patterns are caused by integration of multimodal social stimuli or by a specific sensory modality associated with a social interaction. Rodents rely heavily on chemosensory cues in the form of olfactory signals for social recognition processes. To determine the extent to which social olfactory signals contribute to CA2 place cell responses to social stimuli, we recorded CA2 place cells in rats freely exploring environments containing stimuli that included or lacked olfactory content. We found that CA2 place cell firing patterns significantly changed only when social odors were prominent. Also, place cells that increased their firing in the presence of social odors alone preferentially increased their firing during subsequent sharp wave-ripples. Our results suggest that social olfactory cues are essential for changing CA2 place cell firing patterns during and after social interactions. These results support prior work suggesting CA2 performs social functions and shed light on processes underlying CA2 responses to social stimuli.
{"title":"Social odors drive hippocampal CA2 place cell responses to social stimuli","authors":"Emma Robson , Margaret M. Donahue , Alexandra J. Mably , Peyton G. Demetrovich , Lauren T. Hewitt , Laura Lee Colgin","doi":"10.1016/j.pneurobio.2024.102708","DOIUrl":"10.1016/j.pneurobio.2024.102708","url":null,"abstract":"<div><div>Hippocampal region CA2 is essential for social memory processing. Interaction with social stimuli induces changes in CA2 place cell firing during active exploration and sharp wave-ripples during rest following a social interaction. However, it is unknown whether these changes in firing patterns are caused by integration of multimodal social stimuli or by a specific sensory modality associated with a social interaction. Rodents rely heavily on chemosensory cues in the form of olfactory signals for social recognition processes. To determine the extent to which social olfactory signals contribute to CA2 place cell responses to social stimuli, we recorded CA2 place cells in rats freely exploring environments containing stimuli that included or lacked olfactory content. We found that CA2 place cell firing patterns significantly changed only when social odors were prominent. Also, place cells that increased their firing in the presence of social odors alone preferentially increased their firing during subsequent sharp wave-ripples. Our results suggest that social olfactory cues are essential for changing CA2 place cell firing patterns during and after social interactions. These results support prior work suggesting CA2 performs social functions and shed light on processes underlying CA2 responses to social stimuli.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102708"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142915351","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 : 2025-02-01DOI: 10.1016/j.pneurobio.2025.102717
Rose Nasrawi, Mika Mautner-Rohde, Freek van Ede
It is well established that when we hold more content in working memory, we are slower to act upon part of that content when it becomes relevant for behavior. Here, we asked whether this load-related slowing is due to slower access to the sensory representations held in working memory (as predicted by serial working-memory search), or by a reduced preparedness to act upon those sensory representations once accessed. To address this, we designed a visual-motor working-memory task in which participants memorized the orientation of two or four colored bars, of which one was cued for reproduction. We independently tracked EEG markers associated with the selection of visual (cued item location) and motor (relevant manual action) information from the EEG time-frequency signal, and compared their latencies as a function of memory load. We confirm slower memory-guided behavior with higher working-memory load and show that this is associated with delayed motor selection. In contrast, we find no evidence for a concomitant delay in the latency of visual selection. Moreover, we show that variability in decision times within each memory-load condition is associated with corresponding changes in the latency of motor, but not visual selection. These results reveal how memory load affects our preparedness to act on sensory representations in working memory, while leaving sensory access itself unaffected. This posits action readiness as a key factor that shapes the speed of memory-guided behavior and that underlies delayed responding with higher working-memory load.
{"title":"Memory load influences our preparedness to act on visual representations in working memory without affecting their accessibility","authors":"Rose Nasrawi, Mika Mautner-Rohde, Freek van Ede","doi":"10.1016/j.pneurobio.2025.102717","DOIUrl":"10.1016/j.pneurobio.2025.102717","url":null,"abstract":"<div><div>It is well established that when we hold more content in working memory, we are slower to act upon part of that content when it becomes relevant for behavior. Here, we asked whether this load-related slowing is due to slower access to the sensory representations held in working memory (as predicted by serial working-memory search), or by a reduced preparedness to act upon those sensory representations once accessed. To address this, we designed a visual-motor working-memory task in which participants memorized the orientation of two or four colored bars, of which one was cued for reproduction. We independently tracked EEG markers associated with the selection of visual (cued item location) and motor (relevant manual action) information from the EEG time-frequency signal, and compared their latencies as a function of memory load. We confirm slower memory-guided behavior with higher working-memory load and show that this is associated with delayed motor selection. In contrast, we find no evidence for a concomitant delay in the latency of visual selection. Moreover, we show that variability in decision times within each memory-load condition is associated with corresponding changes in the latency of motor, but not visual selection. These results reveal how memory load affects our preparedness to act on sensory representations in working memory, while leaving sensory access itself unaffected. This posits action readiness as a key factor that shapes the speed of memory-guided behavior and that underlies delayed responding with higher working-memory load.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102717"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953557","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 : 2025-02-01DOI: 10.1016/j.pneurobio.2024.102709
Kenji W. Koyano , Jessica Taubert , William Robison , Elena N. Waidmann , David A. Leopold
The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces. This phenomenon is known as face pareidolia. Behavioral experiments have suggested that macaques, like humans, perceive illusory faces in such objects. However, it is an open question whether such stimuli would naturally stimulate neurons residing in cortical face patches. To address this question, we recorded single unit activity from four fMRI-defined face-selective regions: the anterior medial (AM), anterior fundus (AF), prefrontal orbital (PO), and perirhinal cortex (PRh) face patches. We compared neural responses elicited by images of real macaque faces, pareidolia-evoking objects, and matched control objects. Contrary to expectations, we found no evidence of a general preference for pareidolia-evoking objects over control objects. Although a subset of neurons exhibited stronger responses to pareidolia-evoking objects, the population responses to both categories of objects were similar, and collectively much less than to real macaque faces. These results suggest that neural responses in the four regions we tested are principally concerned with the analysis of realistic facial characteristics, whereas the special attention afforded to face-like pareidolia stimuli is supported by activity elsewhere in the brain.
{"title":"Face pareidolia minimally engages macaque face selective neurons","authors":"Kenji W. Koyano , Jessica Taubert , William Robison , Elena N. Waidmann , David A. Leopold","doi":"10.1016/j.pneurobio.2024.102709","DOIUrl":"10.1016/j.pneurobio.2024.102709","url":null,"abstract":"<div><div>The macaque cerebral cortex contains concentrations of neurons that prefer faces over inanimate objects. Although these so-called face patches are thought to be specialized for the analysis of facial signals, their exact tuning properties remain unclear. For example, what happens when an object by chance resembles a face? Everyday objects can sometimes, through the accidental positioning of their internal components, appear as faces. This phenomenon is known as face pareidolia. Behavioral experiments have suggested that macaques, like humans, perceive illusory faces in such objects. However, it is an open question whether such stimuli would naturally stimulate neurons residing in cortical face patches. To address this question, we recorded single unit activity from four fMRI-defined face-selective regions: the anterior medial (AM), anterior fundus (AF), prefrontal orbital (PO), and perirhinal cortex (PRh) face patches. We compared neural responses elicited by images of real macaque faces, pareidolia-evoking objects, and matched control objects. Contrary to expectations, we found no evidence of a general preference for pareidolia-evoking objects over control objects. Although a subset of neurons exhibited stronger responses to pareidolia-evoking objects, the population responses to both categories of objects were similar, and collectively much less than to real macaque faces. These results suggest that neural responses in the four regions we tested are principally concerned with the analysis of realistic facial characteristics, whereas the special attention afforded to face-like pareidolia stimuli is supported by activity elsewhere in the brain.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"245 ","pages":"Article 102709"},"PeriodicalIF":6.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142927966","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}
The brain faces the challenging task of preserving a consistent portrayal of the external world in the face of disruptive sensory inputs. What alterations occur in sensory representation amidst noise, and how does brain activity adapt to it? Although it has previously been shown that background white noise (WN) decreases responses to salient sounds, a mechanistic understanding of the brain processes responsible for such changes is lacking. We investigated the effect of background WN on neuronal spiking activity, membrane potential, and network oscillations in the mouse central auditory system. We found that, in addition to increasing background spiking activity in the auditory cortex and thalamus, background WN decreases neural activity fluctuations, as reflected in the membrane potential of single neurons and the local field potential. Blocking acetylcholine signaling in the auditory cortex eliminated the WN-dependent increase in background activity as well as the shift in slow-wave oscillations. Together, our observations show that background WN is not filtered away along the auditory pathway, but rather drives sustained changes in cortical activity that can be reverted by blocking cholinergic inputs.
{"title":"Background white noise increases neuronal activity by reducing membrane fluctuations and slow-wave oscillations in auditory cortex","authors":"Rasmus Kordt Christensen , Florian Studer, Tania Rinaldi Barkat","doi":"10.1016/j.pneurobio.2025.102720","DOIUrl":"10.1016/j.pneurobio.2025.102720","url":null,"abstract":"<div><div>The brain faces the challenging task of preserving a consistent portrayal of the external world in the face of disruptive sensory inputs. What alterations occur in sensory representation amidst noise, and how does brain activity adapt to it? Although it has previously been shown that background white noise (WN) decreases responses to salient sounds, a mechanistic understanding of the brain processes responsible for such changes is lacking. We investigated the effect of background WN on neuronal spiking activity, membrane potential, and network oscillations in the mouse central auditory system. We found that, in addition to increasing background spiking activity in the auditory cortex and thalamus, background WN decreases neural activity fluctuations, as reflected in the membrane potential of single neurons and the local field potential. Blocking acetylcholine signaling in the auditory cortex eliminated the WN-dependent increase in background activity as well as the shift in slow-wave oscillations. Together, our observations show that background WN is not filtered away along the auditory pathway, but rather drives sustained changes in cortical activity that can be reverted by blocking cholinergic inputs.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"246 ","pages":"Article 102720"},"PeriodicalIF":6.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041482","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 : 2025-01-22DOI: 10.1016/j.pneurobio.2025.102718
Odra Santander , Sebastián B. Arredondo , Francisca García-Rojas , Sebastián F. Estay , Juan E. Belforte , Andrés E. Chávez , Lorena Varela-Nallar , Marco Fuenzalida
Ketamine administration during adolescence affects cognitive performance; however, its long-term impact on synaptic function and neuronal integration in the hippocampus a brain region critical for cognition remains unclear. Using functional and molecular analyses, we found that chronic ketamine administration during adolescence exerts long-term effects on synaptic integration, expanding the temporal window in an input-specific manner affecting the inner molecular layer but not the medial perforant path inputs in the adult mouse dorsal hippocampal dentate gyrus. Ketamine also alters the excitatory/inhibitory balance by reducing the efficacy of inhibitory inputs likely due to a reduction in parvalbumin-positive interneurons number and function. These findings indicate that during adolescence, ketamine exerts a strong effect on inhibitory synaptic function mediated by parvalbumin-positive neurons that ultimately impact synaptic integration in the dorsal adult dentate gyrus, which could help to understand the neurobiological and functional bases that confer greater vulnerability to the adolescent brain.
{"title":"Ketamine administration during adolescence impairs synaptic integration and inhibitory synaptic transmission in the adult dentate gyrus","authors":"Odra Santander , Sebastián B. Arredondo , Francisca García-Rojas , Sebastián F. Estay , Juan E. Belforte , Andrés E. Chávez , Lorena Varela-Nallar , Marco Fuenzalida","doi":"10.1016/j.pneurobio.2025.102718","DOIUrl":"10.1016/j.pneurobio.2025.102718","url":null,"abstract":"<div><div>Ketamine administration during adolescence affects cognitive performance; however, its long-term impact on synaptic function and neuronal integration in the hippocampus a brain region critical for cognition remains unclear. Using functional and molecular analyses, we found that chronic ketamine administration during adolescence exerts long-term effects on synaptic integration, expanding the temporal window in an input-specific manner affecting the inner molecular layer but not the medial perforant path inputs in the adult mouse dorsal hippocampal dentate gyrus. Ketamine also alters the excitatory/inhibitory balance by reducing the efficacy of inhibitory inputs likely due to a reduction in parvalbumin-positive interneurons number and function. These findings indicate that during adolescence, ketamine exerts a strong effect on inhibitory synaptic function mediated by parvalbumin-positive neurons that ultimately impact synaptic integration in the dorsal adult dentate gyrus, which could help to understand the neurobiological and functional bases that confer greater vulnerability to the adolescent brain.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"246 ","pages":"Article 102718"},"PeriodicalIF":6.7,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143041485","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 : 2025-01-21DOI: 10.1016/j.pneurobio.2025.102719
Joana Covelo , Alessandra Camassa , Jose Manuel Sanchez-Sanchez , Arnau Manasanch , Leonardo Dalla Porta , Nathalia Cancino-Fuentes , Almudena Barbero-Castillo , Rita M. Robles , Miquel Bosch , Silvia Tapia-Gonzalez , Paula Merino-Serrais , Mar Carreño , Estefania Conde-Blanco , Jordi Rumià Arboix , Pedro Roldán , Javier DeFelipe , Maria V. Sanchez-Vives
Elucidating human cerebral cortex function is essential for understanding the physiological basis of both healthy and pathological brain states. We obtained extracellular local field potential recordings from slices of neocortical tissue from refractory epilepsy patients. Multi-electrode recordings were combined with histological information, providing a two-dimensional spatiotemporal characterization of human cortical dynamics in control conditions and following modulation of the excitation/inhibition balance. Slices expressed spontaneous rhythmic activity consistent with slow wave activity, comprising alternating active (Up) and silent (Down) states (Up-duration: 0.08 ± 0.03 s, Down-duration: 2.62 ± 2.12 s, frequency: 0.75 ± 0.39 Hz). Up states propagated from deep to superficial layers, with faster propagation speeds than in other species (vertical: 64.6 mm/s; horizontal: 65.9 mm/s). GABAA blockade progressively transformed the emergent activity into epileptiform discharges, marked by higher firing rates, faster network recruitment and propagation, and infraslow rhythmicity (0.01 Hz). This dynamical characterization broadens our understanding of the mechanistic organization of the human cortical network at the micro- and mesoscale.
{"title":"Spatiotemporal network dynamics and structural correlates in the human cerebral cortex in vitro","authors":"Joana Covelo , Alessandra Camassa , Jose Manuel Sanchez-Sanchez , Arnau Manasanch , Leonardo Dalla Porta , Nathalia Cancino-Fuentes , Almudena Barbero-Castillo , Rita M. Robles , Miquel Bosch , Silvia Tapia-Gonzalez , Paula Merino-Serrais , Mar Carreño , Estefania Conde-Blanco , Jordi Rumià Arboix , Pedro Roldán , Javier DeFelipe , Maria V. Sanchez-Vives","doi":"10.1016/j.pneurobio.2025.102719","DOIUrl":"10.1016/j.pneurobio.2025.102719","url":null,"abstract":"<div><div>Elucidating human cerebral cortex function is essential for understanding the physiological basis of both healthy and pathological brain states. We obtained extracellular local field potential recordings from slices of neocortical tissue from refractory epilepsy patients. Multi-electrode recordings were combined with histological information, providing a two-dimensional spatiotemporal characterization of human cortical dynamics in control conditions and following modulation of the excitation/inhibition balance<em>.</em> Slices expressed spontaneous rhythmic activity consistent with slow wave activity, comprising alternating active (Up) and silent (Down) states (Up-duration: 0.08 ± 0.03 s, Down-duration: 2.62 ± 2.12 s, frequency: 0.75 ± 0.39 Hz). Up states propagated from deep to superficial layers, with faster propagation speeds than in other species (vertical: 64.6 mm/s; horizontal: 65.9 mm/s). GABA<sub>A</sub> blockade progressively transformed the emergent activity into epileptiform discharges, marked by higher firing rates, faster network recruitment and propagation, and infraslow rhythmicity (0.01 Hz). This dynamical characterization broadens our understanding of the mechanistic organization of the human cortical network at the micro- and mesoscale.</div></div>","PeriodicalId":20851,"journal":{"name":"Progress in Neurobiology","volume":"246 ","pages":"Article 102719"},"PeriodicalIF":6.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143029408","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}
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