Pub Date : 2022-05-11DOI: 10.3389/fnsyn.2022.851015
Wenlong Shi, Yuan Fu, Tian-yao Shi, Wenxia Zhou
Post-traumatic stress disorder (PTSD) can be triggered not only in people who have personally experienced traumatic events but also in those who witness them. Physiological and psychological stress can have different effects on neural activity, but little is known about the underlying mechanisms. There is ample evidence that the insular cortex, especially the anterior insular cortex (aIC), is critical to both the sensory and emotional experience of pain. It is therefore worthwhile to explore the effects of direct and indirect stress on the synaptic plasticity of the aIC. Here, we used a mouse model of observational fear to mimic direct suffering (Demonstrator, DM) and witnessing (Observer, OB) of traumatic events. After observational fear training, using a 64-channel recording system, we showed that both DM and OB mice exhibited a decreased ratio of paired-pulse with intervals of 50 ms in the superficial layers of the aIC but not in the deep layers. We found that theta-burst stimulation (TBS)–induced long-term potentiation (LTP) in OB mice was significantly higher than in DM mice, and the recruitment of synaptic responses occurred only in OB mice. Compared with naive mice, OB mice showed stronger recruitment and higher amplitude in the superficial layers of the aIC. We also used low-frequency stimulation (LFS) to induce long-term depression (LTD). OB mice showed greater LTD in both the superficial and deep layers of the aIC than naive mice, but no significant difference was found between OB and DM mice. These results provide insights into the changes in synaptic plasticity in the aIC after physiological and psychological stress, and suggest that different types of stress may have different mechanisms. Furthermore, identification of the possible causes of the differences in stress could help treat stress-related disorders.
{"title":"Different Synaptic Plasticity After Physiological and Psychological Stress in the Anterior Insular Cortex in an Observational Fear Mouse Model","authors":"Wenlong Shi, Yuan Fu, Tian-yao Shi, Wenxia Zhou","doi":"10.3389/fnsyn.2022.851015","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.851015","url":null,"abstract":"Post-traumatic stress disorder (PTSD) can be triggered not only in people who have personally experienced traumatic events but also in those who witness them. Physiological and psychological stress can have different effects on neural activity, but little is known about the underlying mechanisms. There is ample evidence that the insular cortex, especially the anterior insular cortex (aIC), is critical to both the sensory and emotional experience of pain. It is therefore worthwhile to explore the effects of direct and indirect stress on the synaptic plasticity of the aIC. Here, we used a mouse model of observational fear to mimic direct suffering (Demonstrator, DM) and witnessing (Observer, OB) of traumatic events. After observational fear training, using a 64-channel recording system, we showed that both DM and OB mice exhibited a decreased ratio of paired-pulse with intervals of 50 ms in the superficial layers of the aIC but not in the deep layers. We found that theta-burst stimulation (TBS)–induced long-term potentiation (LTP) in OB mice was significantly higher than in DM mice, and the recruitment of synaptic responses occurred only in OB mice. Compared with naive mice, OB mice showed stronger recruitment and higher amplitude in the superficial layers of the aIC. We also used low-frequency stimulation (LFS) to induce long-term depression (LTD). OB mice showed greater LTD in both the superficial and deep layers of the aIC than naive mice, but no significant difference was found between OB and DM mice. These results provide insights into the changes in synaptic plasticity in the aIC after physiological and psychological stress, and suggest that different types of stress may have different mechanisms. Furthermore, identification of the possible causes of the differences in stress could help treat stress-related disorders.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47137046","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-09DOI: 10.3389/fnsyn.2022.857675
Thomas M. Sanderson, Liam Ralph, M. Amici, Ai Na Ng, B. Kaang, M. Zhuo, S. Kim, J. Georgiou, G. Collingridge
In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG. We found that 30 μM DHPG generated presynaptic LTD that required the co-activation of NMDA receptors, whereas 100 μM DHPG resulted in postsynaptic LTD that was independent of the activation of NMDA receptors. We found that both forms of LTD occur at the same synapses and that these may constitute the population with the lowest basal P(r). Our results reveal an unexpected complexity to mGluR-mediated synaptic plasticity in the hippocampus.
{"title":"Selective Recruitment of Presynaptic and Postsynaptic Forms of mGluR-LTD","authors":"Thomas M. Sanderson, Liam Ralph, M. Amici, Ai Na Ng, B. Kaang, M. Zhuo, S. Kim, J. Georgiou, G. Collingridge","doi":"10.3389/fnsyn.2022.857675","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.857675","url":null,"abstract":"In area CA1 of the hippocampus, long-term depression (LTD) can be induced by activating group I metabotropic glutamate receptors (mGluRs), with the selective agonist DHPG. There is evidence that mGluR-LTD can be expressed by either a decrease in the probability of neurotransmitter release [P(r)] or by a change in postsynaptic AMPA receptor number. However, what determines the locus of expression is unknown. We investigated the expression mechanisms of mGluR-LTD using either a low (30 μM) or a high (100 μM) concentration of (RS)-DHPG. We found that 30 μM DHPG generated presynaptic LTD that required the co-activation of NMDA receptors, whereas 100 μM DHPG resulted in postsynaptic LTD that was independent of the activation of NMDA receptors. We found that both forms of LTD occur at the same synapses and that these may constitute the population with the lowest basal P(r). Our results reveal an unexpected complexity to mGluR-mediated synaptic plasticity in the hippocampus.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41411082","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-09DOI: 10.3389/fnsyn.2022.898090
J. G. Edwards, L. Cristino, Dan P Covey
Endocannabinoids (eCBs) are lipid-signaling molecules that often work in a retrograde fashion. Themost common eCBs are 2-arachidonoylglycerol (2-AG) and anandamide, which bind receptors such as cannabinoid receptor 1 (CB1) and CB2. Endocannabinoid signaling controls synaptic transmission throughout the central nervous system, and is important in modulating activity and behavior in the mesolimbic reward circuit, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and lateral habenula (LHb). In these regions, the eCB system is essential for normal reward learning and for some maladaptive behaviors underlying drug abuse and addiction. Recently identified lipid-signaling eCB-like molecules are also now understood to shape mesolimbic system function and reward-related behaviors. Further elucidating how the eCB system contributes to reward and addiction is especially pertinent given the recent legalization ofmedicinal or recreationalmarijuana throughout the world. Themajor psychoactive component inmarijuana is1-9-tetrahydrocannabinol (THC), which binds CB1. Common effects of THC are short-termmemory loss, appetite stimulation, and reward. There is still much to investigate concerning THC use, particularly the impact of adolescent use, with a focus on long-term alterations in eCB system function and behavioral changes. Further research is required to clarify the role of the endogenous eCB system, and the effect of exogenous CB1 or CB2targeting drugs on mesolimbic function, including synaptic plasticity, to support reward behaviors and addiction. This Research Topic focuses on endogenous eCB system function in the mesolimbic circuit with an emphasis on synaptic plasticity, reward behavior, novel eCB-like molecules, and pain.
{"title":"Editorial: The Emerging Role of Endocannabinoids in Synaptic Plasticity, Reward, and Addiction","authors":"J. G. Edwards, L. Cristino, Dan P Covey","doi":"10.3389/fnsyn.2022.898090","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.898090","url":null,"abstract":"Endocannabinoids (eCBs) are lipid-signaling molecules that often work in a retrograde fashion. Themost common eCBs are 2-arachidonoylglycerol (2-AG) and anandamide, which bind receptors such as cannabinoid receptor 1 (CB1) and CB2. Endocannabinoid signaling controls synaptic transmission throughout the central nervous system, and is important in modulating activity and behavior in the mesolimbic reward circuit, including the ventral tegmental area (VTA), nucleus accumbens (NAc), and lateral habenula (LHb). In these regions, the eCB system is essential for normal reward learning and for some maladaptive behaviors underlying drug abuse and addiction. Recently identified lipid-signaling eCB-like molecules are also now understood to shape mesolimbic system function and reward-related behaviors. Further elucidating how the eCB system contributes to reward and addiction is especially pertinent given the recent legalization ofmedicinal or recreationalmarijuana throughout the world. Themajor psychoactive component inmarijuana is1-9-tetrahydrocannabinol (THC), which binds CB1. Common effects of THC are short-termmemory loss, appetite stimulation, and reward. There is still much to investigate concerning THC use, particularly the impact of adolescent use, with a focus on long-term alterations in eCB system function and behavioral changes. Further research is required to clarify the role of the endogenous eCB system, and the effect of exogenous CB1 or CB2targeting drugs on mesolimbic function, including synaptic plasticity, to support reward behaviors and addiction. This Research Topic focuses on endogenous eCB system function in the mesolimbic circuit with an emphasis on synaptic plasticity, reward behavior, novel eCB-like molecules, and pain.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42234825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-05-06DOI: 10.3389/fnsyn.2022.891740
Rei Yamada, H. Kuba
Binaural coincidence detection is the initial step in encoding interaural time differences (ITDs) for sound-source localization. In birds, neurons in the nucleus laminaris (NL) play a central role in this process. These neurons receive excitatory synaptic inputs on dendrites from both sides of the cochlear nucleus and compare their coincidences at the soma. The NL is tonotopically organized, and individual neurons receive a pattern of synaptic inputs that are specific to their tuning frequency. NL neurons differ in their dendritic morphology along the tonotopic axis; their length increases with lower tuning frequency. In addition, our series of studies have revealed several frequency-dependent refinements in the morphological and biophysical characteristics of NL neurons, such as the amount and subcellular distribution of ion channels and excitatory and inhibitory synapses, which enable the neurons to process the frequency-specific pattern of inputs appropriately and encode ITDs at each frequency band. In this review, we will summarize these refinements of NL neurons and their implications for the ITD coding. We will also discuss the similarities and differences between avian and mammalian coincidence detectors.
{"title":"Cellular Strategies for Frequency-Dependent Computation of Interaural Time Difference","authors":"Rei Yamada, H. Kuba","doi":"10.3389/fnsyn.2022.891740","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.891740","url":null,"abstract":"Binaural coincidence detection is the initial step in encoding interaural time differences (ITDs) for sound-source localization. In birds, neurons in the nucleus laminaris (NL) play a central role in this process. These neurons receive excitatory synaptic inputs on dendrites from both sides of the cochlear nucleus and compare their coincidences at the soma. The NL is tonotopically organized, and individual neurons receive a pattern of synaptic inputs that are specific to their tuning frequency. NL neurons differ in their dendritic morphology along the tonotopic axis; their length increases with lower tuning frequency. In addition, our series of studies have revealed several frequency-dependent refinements in the morphological and biophysical characteristics of NL neurons, such as the amount and subcellular distribution of ion channels and excitatory and inhibitory synapses, which enable the neurons to process the frequency-specific pattern of inputs appropriately and encode ITDs at each frequency band. In this review, we will summarize these refinements of NL neurons and their implications for the ITD coding. We will also discuss the similarities and differences between avian and mammalian coincidence detectors.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42075057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-25DOI: 10.3389/fnsyn.2022.862704
Yi Yang, Jinliang Bai, Jianyuan Sun, Ting Ye, Lu Zhang, Fengfeng Wu, Jun Nan, Yan Lan
μ-opioid receptors (MOR) are widely expressed in the brain, varying in density in different areas. Activation of MORs underlies analgesia, euphoria, but may lead to tolerance, dependence, and ultimately opioid addiction. The Purkinje cell (PC) is the only efferent neuron in the cerebellar cortex and receives glutamatergic synaptic inputs from the parallel fibers formed by the axons of granule cells. Studies have shown that MORs are expressed during the development of cerebellar cells. However, the distribution of MOR and their effects on PF-PC synaptic transmission remain unclear. To examine these questions, we used whole-cell patch clamp recordings and pharmacological methods to determine the effects and mechanisms of MOR activation on synaptic transmission at PF-PC synapses. The MOR-selective agonist DAMGO significantly reduced the amplitude and area under the curve (AUC) of PF-PC evoked (e) EPSCs, and increased the paired-pulse ratio (PPR).DAMGO-induced inhibitory effects on PF-PC eEPSCs and PPR were abolished by MOR specific blocker CTOP. Further, DAMGO significantly reduced the frequency of PF-PC mEPSCs, but had no obvious effect on their amplitude, suggesting a presynaptic site of action. The DAMGO-induced reduction in the frequency of PF-PC mEPSCs also was blocked by CTOP. A protein kinase A (PKA) inhibitor PKI added in the pipette solution did not affect the inhibitory effects on PF-PC mEPSCs induced by DAMGO. Both the PKA inhibitor K5720 and MEK inhibitor U0126 in artificial cerebrospinal fluid (ACSF) prevented the inhibitory effects of DAMGO on PF-PC mEPSCs. These findings reveal that MORs are expressed in presynaptic PF axon terminals, where DAMGO can activate presynaptic MORs to inhibit PF-PC synaptic transmission by regulating the release of glutamate. G-protein-dependent cAMP-PKA signaling pathway may be involved in this process.
{"title":"Mechanisms Underlying Mu Opioid Receptor Effects on Parallel Fiber-Purkinje Cell Synaptic Transmission in Mouse Cerebellar Cortex","authors":"Yi Yang, Jinliang Bai, Jianyuan Sun, Ting Ye, Lu Zhang, Fengfeng Wu, Jun Nan, Yan Lan","doi":"10.3389/fnsyn.2022.862704","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.862704","url":null,"abstract":"μ-opioid receptors (MOR) are widely expressed in the brain, varying in density in different areas. Activation of MORs underlies analgesia, euphoria, but may lead to tolerance, dependence, and ultimately opioid addiction. The Purkinje cell (PC) is the only efferent neuron in the cerebellar cortex and receives glutamatergic synaptic inputs from the parallel fibers formed by the axons of granule cells. Studies have shown that MORs are expressed during the development of cerebellar cells. However, the distribution of MOR and their effects on PF-PC synaptic transmission remain unclear. To examine these questions, we used whole-cell patch clamp recordings and pharmacological methods to determine the effects and mechanisms of MOR activation on synaptic transmission at PF-PC synapses. The MOR-selective agonist DAMGO significantly reduced the amplitude and area under the curve (AUC) of PF-PC evoked (e) EPSCs, and increased the paired-pulse ratio (PPR).DAMGO-induced inhibitory effects on PF-PC eEPSCs and PPR were abolished by MOR specific blocker CTOP. Further, DAMGO significantly reduced the frequency of PF-PC mEPSCs, but had no obvious effect on their amplitude, suggesting a presynaptic site of action. The DAMGO-induced reduction in the frequency of PF-PC mEPSCs also was blocked by CTOP. A protein kinase A (PKA) inhibitor PKI added in the pipette solution did not affect the inhibitory effects on PF-PC mEPSCs induced by DAMGO. Both the PKA inhibitor K5720 and MEK inhibitor U0126 in artificial cerebrospinal fluid (ACSF) prevented the inhibitory effects of DAMGO on PF-PC mEPSCs. These findings reveal that MORs are expressed in presynaptic PF axon terminals, where DAMGO can activate presynaptic MORs to inhibit PF-PC synaptic transmission by regulating the release of glutamate. G-protein-dependent cAMP-PKA signaling pathway may be involved in this process.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47781928","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-04DOI: 10.3389/fnsyn.2022.861215
Meishar Shahoha, Ronni Cohen, Yoav Ben-Simon, U. Ashery
Cyclic adenosine monophosphate (cAMP) is a crucial second messenger involved in both pre- and postsynaptic plasticity in many neuronal types across species. In the hippocampal mossy fiber (MF) synapse, cAMP mediates presynaptic long-term potentiation and depression. The main cAMP-dependent signaling pathway linked to MF synaptic plasticity acts via the activation of the protein kinase A (PKA) molecular cascade. Accordingly, various downstream putative synaptic PKA target proteins have been linked to cAMP-dependent MF synaptic plasticity, such as synapsin, rabphilin, synaptotagmin-12, RIM1a, tomosyn, and P/Q-type calcium channels. Regulating the expression of some of these proteins alters synaptic release probability and calcium channel clustering, resulting in short- and long-term changes to synaptic efficacy. However, despite decades of research, the exact molecular mechanisms by which cAMP and PKA exert their influences in MF terminals remain largely unknown. Here, we review current knowledge of different cAMP catalysts and potential downstream PKA-dependent molecular cascades, in addition to non-canonical cAMP-dependent but PKA-independent cascades, which might serve as alternative, compensatory or competing pathways to the canonical PKA cascade. Since several other central synapses share a similar form of presynaptic plasticity with the MF, a better description of the molecular mechanisms governing MF plasticity could be key to understanding the relationship between the transcriptional and computational levels across brain regions.
{"title":"cAMP-Dependent Synaptic Plasticity at the Hippocampal Mossy Fiber Terminal","authors":"Meishar Shahoha, Ronni Cohen, Yoav Ben-Simon, U. Ashery","doi":"10.3389/fnsyn.2022.861215","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.861215","url":null,"abstract":"Cyclic adenosine monophosphate (cAMP) is a crucial second messenger involved in both pre- and postsynaptic plasticity in many neuronal types across species. In the hippocampal mossy fiber (MF) synapse, cAMP mediates presynaptic long-term potentiation and depression. The main cAMP-dependent signaling pathway linked to MF synaptic plasticity acts via the activation of the protein kinase A (PKA) molecular cascade. Accordingly, various downstream putative synaptic PKA target proteins have been linked to cAMP-dependent MF synaptic plasticity, such as synapsin, rabphilin, synaptotagmin-12, RIM1a, tomosyn, and P/Q-type calcium channels. Regulating the expression of some of these proteins alters synaptic release probability and calcium channel clustering, resulting in short- and long-term changes to synaptic efficacy. However, despite decades of research, the exact molecular mechanisms by which cAMP and PKA exert their influences in MF terminals remain largely unknown. Here, we review current knowledge of different cAMP catalysts and potential downstream PKA-dependent molecular cascades, in addition to non-canonical cAMP-dependent but PKA-independent cascades, which might serve as alternative, compensatory or competing pathways to the canonical PKA cascade. Since several other central synapses share a similar form of presynaptic plasticity with the MF, a better description of the molecular mechanisms governing MF plasticity could be key to understanding the relationship between the transcriptional and computational levels across brain regions.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":"14 1","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69623064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-21DOI: 10.3389/fnsyn.2022.833782
T. Chater, Y. Goda
Neurotransmission is critically dependent on the number, position, and composition of receptor proteins on the postsynaptic neuron. Of these, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are responsible for the majority of postsynaptic depolarization at excitatory mammalian synapses following glutamate release. AMPARs are continually trafficked to and from the cell surface, and once at the surface, AMPARs laterally diffuse in and out of synaptic domains. Moreover, the subcellular distribution of AMPARs is shaped by patterns of activity, as classically demonstrated by the synaptic insertion or removal of AMPARs following the induction of long-term potentiation (LTP) and long-term depression (LTD), respectively. Crucially, there are many subtleties in the regulation of AMPARs, and exactly how local and global synaptic activity drives the trafficking and retention of synaptic AMPARs of different subtypes continues to attract attention. Here we will review how activity can have differential effects on AMPAR distribution and trafficking along with its subunit composition and phosphorylation state, and we highlight some of the controversies and remaining questions. As the AMPAR field is extensive, to say the least, this review will focus primarily on cellular and molecular studies in the hippocampus. We apologise to authors whose work could not be cited directly owing to space limitations.
{"title":"The Shaping of AMPA Receptor Surface Distribution by Neuronal Activity","authors":"T. Chater, Y. Goda","doi":"10.3389/fnsyn.2022.833782","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.833782","url":null,"abstract":"Neurotransmission is critically dependent on the number, position, and composition of receptor proteins on the postsynaptic neuron. Of these, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors (AMPARs) are responsible for the majority of postsynaptic depolarization at excitatory mammalian synapses following glutamate release. AMPARs are continually trafficked to and from the cell surface, and once at the surface, AMPARs laterally diffuse in and out of synaptic domains. Moreover, the subcellular distribution of AMPARs is shaped by patterns of activity, as classically demonstrated by the synaptic insertion or removal of AMPARs following the induction of long-term potentiation (LTP) and long-term depression (LTD), respectively. Crucially, there are many subtleties in the regulation of AMPARs, and exactly how local and global synaptic activity drives the trafficking and retention of synaptic AMPARs of different subtypes continues to attract attention. Here we will review how activity can have differential effects on AMPAR distribution and trafficking along with its subunit composition and phosphorylation state, and we highlight some of the controversies and remaining questions. As the AMPAR field is extensive, to say the least, this review will focus primarily on cellular and molecular studies in the hippocampus. We apologise to authors whose work could not be cited directly owing to space limitations.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"42936576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-18DOI: 10.3389/fnsyn.2022.875904
F. Rubio, E. Valjent, B. Hope
{"title":"Editorial: Activated Synapses","authors":"F. Rubio, E. Valjent, B. Hope","doi":"10.3389/fnsyn.2022.875904","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.875904","url":null,"abstract":"","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43669739","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-09DOI: 10.3389/fnsyn.2022.846099
Hansen Wang, R. Balice-Gordon
Mutations in genes encoding synaptic or synapse-related proteins that affect the structure and/or function of synapses are responsible for various forms of synaptopathies, including neurodevelopmental, neurodegenerative and psychiatric diseases (Lepeta et al., 2016; Lima Caldeira et al., 2019; Bonnycastle et al., 2021; Germann et al., 2021). Understanding how disease causing genes affect synapse structure and function, and cause circuit and behavioral dysfunction, has been a focus of neuroscience research over several decades. Many challenges remain to be addressed, from identifying rare disease-associated genes, defining the molecular and cellular mechanisms by which the genetic mutations confer disease risk and manifest as phenotypes, understanding how thesemutations affect circuit function, plasticity and behavior, to whether therapeutic interventions can restore function. Studying the pathophysiologic mechanisms underlying synaptopathies will lead to a better understanding of the molecular and cellular mechanisms that govern normal nervous system function, and may eventually help to discover impactful therapeutics (Wang and Doering, 2015; Lepeta et al., 2016; Lima Caldeira et al., 2019; Carroll et al., 2021). This Research Topic has focused on advances in studying common synaptopathies, collecting 31 research and review articles ranging from new insights into fundamental synapse biology to potential therapeutic strategies. Here we summarize each of these articles as a guide to the Research Topic, and highlight the many new research questions stimulated by the work.
{"title":"Editorial: Synaptic Diseases: From Biology to Potential Therapy","authors":"Hansen Wang, R. Balice-Gordon","doi":"10.3389/fnsyn.2022.846099","DOIUrl":"https://doi.org/10.3389/fnsyn.2022.846099","url":null,"abstract":"Mutations in genes encoding synaptic or synapse-related proteins that affect the structure and/or function of synapses are responsible for various forms of synaptopathies, including neurodevelopmental, neurodegenerative and psychiatric diseases (Lepeta et al., 2016; Lima Caldeira et al., 2019; Bonnycastle et al., 2021; Germann et al., 2021). Understanding how disease causing genes affect synapse structure and function, and cause circuit and behavioral dysfunction, has been a focus of neuroscience research over several decades. Many challenges remain to be addressed, from identifying rare disease-associated genes, defining the molecular and cellular mechanisms by which the genetic mutations confer disease risk and manifest as phenotypes, understanding how thesemutations affect circuit function, plasticity and behavior, to whether therapeutic interventions can restore function. Studying the pathophysiologic mechanisms underlying synaptopathies will lead to a better understanding of the molecular and cellular mechanisms that govern normal nervous system function, and may eventually help to discover impactful therapeutics (Wang and Doering, 2015; Lepeta et al., 2016; Lima Caldeira et al., 2019; Carroll et al., 2021). This Research Topic has focused on advances in studying common synaptopathies, collecting 31 research and review articles ranging from new insights into fundamental synapse biology to potential therapeutic strategies. Here we summarize each of these articles as a guide to the Research Topic, and highlight the many new research questions stimulated by the work.","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":" ","pages":""},"PeriodicalIF":3.7,"publicationDate":"2022-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47757253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-03-08DOI: 10.3389/fnsyn.2022.854956
T. Dankovich, S. Rizzoli
In the adult brain, synapses are tightly enwrapped by lattices of the extracellular matrix that consist of extremely long-lived molecules. These lattices are deemed to stabilize synapses, restrict the reorganization of their transmission machinery, and prevent them from undergoing structural or morphological changes. At the same time, they are expected to retain some degree of flexibility to permit occasional events of synaptic plasticity. The recent understanding that structural changes to synapses are significantly more frequent than previously assumed (occurring even on a timescale of minutes) has called for a mechanism that allows continual and energy-efficient remodeling of the extracellular matrix (ECM) at synapses. Here, we review recent evidence for such a process based on the constitutive recycling of synaptic ECM molecules. We discuss the key characteristics of this mechanism, focusing on its roles in mediating synaptic transmission and plasticity, and speculate on additional potential functions in neuronal signaling.
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