Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neu...Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.展开更多
The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other ...The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other brain regions,revealing the crucial role of this area in integrating sensory,emotional,and cognitive information.The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain.We summarize its role in interoceptive and exteroceptive sensory processing,illustrating insular function as a bridge connecting internal and external experiences.Drawing on recent research,we delineate the insular involvement in emotional processes,highlighting its implications in psychiatric conditions,such as anxiety,depression,and addiction.We further discuss the insular contributions to cognition,focusing on its significant roles in time perception and decision-making.Collectively,the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes.Through this review,we hope to highlight the importance of the insula as an interface between sensation,emotion,and cognition,and to inspire further research into this fascinating brain region.展开更多
BACKGROUND： The insular cortex and habenular nucleus may be a regulatory center for obstructive sleep apnea syndrome, and dyspnea may be caused by insular cortex activity. The insular cortex is a cortical representat...BACKGROUND： The insular cortex and habenular nucleus may be a regulatory center for obstructive sleep apnea syndrome, and dyspnea may be caused by insular cortex activity. The insular cortex is a cortical representation of obstructive sleep apnea syndrome. The habenular nucleus is a station for descending insular cortex activity. OBJECTIVE： Through actively stimulating the rat insular cortex, to observe rat respiratory movement, myoelectric activities of genioglossus, arterial partial pressure of oxygen, partial pressure of carbon dioxide and acidity-alkalinity, and to verify a hypothesis that the insular cortex is a superior-position regulation center, and the habenular nucleus is an inferior-position nervous nuclei of the insular cortex in patients with obstructive sleep apnea syndrome. DESIGN, TIME AND SETTING： The randomized, controlled animal study was performed at the Laboratory of Electrophysiology, Department of Physiology, Norman Bathune College of Medicine, Jilin University, China from September 2004 to June 2008. MATERIALS： We used L-glutamic acid （Dingguo Biological Product Research Center, Beijing, China）, lidocaine hydrochloride （Seventh Pharmacy Co., Ltd., Wuxi, China）, electric stimulator （Nihon Kohden, Japan）, and an AVL-OPTI blood gas analyzer （AVL Scientific Co., Roswell, GA, USA）. METHODS： The insular cortex of healthy adult Wistar rats underwent electrostimulation and L-glutamic acid stimulation to record changes in the myoelectric activity of genioglossus and respiratory movement. Some rats were injected with lidocaine to block the habenular nucleus before electrostimulation or L-glutamic acid stimulation. L-glutamic acid and lidocaine were injected by microelectrodes embedded in nuclear groups. MAIN OUTCOME MEASURES： Myoelectric activities of genioglossus, arterial partial pressure of oxygen, partial pressure of carbon dioxide and acidity-alkalinity were measured following apnea in rats undergoing electrostimulation in the insular cortex and following blockade of the habenular nucleus. RESULTS： Following electrostimulation and L-glutamic acid stimulation, rats developed apnea or respiratory rhythm disorders. Simultaneously, the amplitude of myoelectric activity of the genioglossus was reduced （P 〈 0.01 ）, and the electromyogram integral was decreased （P 〈 0.01）. Arterial blood gas analysis showed arterial blood acidosis, a decrease in pH （P 〈 0.05）, and an increase in the negative value of alkaline reserve （P 〈 0.01）. Lidocaine in the habenular nuclear blocked respiratory and other index changes after insular cortex stimulation. CONCLUSION： Dyspnea induced by stimulating the insular cortex may require the habenular nucleus. Paralysis of the habenular nucleus can completely eliminate insular cortex stimulation-induced dyspnea.展开更多
An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to ...An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to create conscious interoception. Especially with regard to pain experience, the IC has been supposed to participate in both sensory-discriminative and affective-motivational aspects of pain. In this review, we discuss the latest data proposing that subregions of the IC are involved in isolated pain networks： the posterior sensory circuit and the anterior emotional network. Due to abundant connections with other brain areas, the IC is likely to serve as an interface where cross-modal shaping of pain occurs. In chronic pain,however, this mode of emotional awareness and the modulation of pain are disrupted. We highlight some of the molecular mechanisms underlying the changes of the pain modulation system that contribute to the transition from acute to chronic pain in the IC.展开更多
The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive un...The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain state.Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve(CPN)ligation.The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral methods.The E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice.Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice.The analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the RAIC.Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.展开更多
Serotonin (5HT) in the central nervous system has been associated with pain processing and modulation. The insular cortex (IC) plays an important role in the development and perception of the inflammatory and chronic ...Serotonin (5HT) in the central nervous system has been associated with pain processing and modulation. The insular cortex (IC) plays an important role in the development and perception of the inflammatory and chronic pain. The role of the serotoninergic system in IC has not been completely studied. We used micro-dialysis in freely moving rats to determine the extracellular release of 5HT and its main metabolite (5HIAA) in the IC during an inflammatory process. Results showed an increase of extracellular levels of 5HT and 5HIAA in the IC during carrageenan-induced inflammation and this augmentation correlates with a decrease of behavioral mechanonociceptive response. Furthermore, the exogenous administration of 5HT and 5HIAA in the IC increases the nociceptive response. Our current data imply that the serotoninergic system in the IC participates in the long-term pain process.展开更多
OBJECTIVE Exposure to stressful events can be differently perceived by individuals depending on the level of stress resilience or vulnerability.The neural processes that underlie such clinical y and social y important...OBJECTIVE Exposure to stressful events can be differently perceived by individuals depending on the level of stress resilience or vulnerability.The neural processes that underlie such clinical y and social y important differences are largely unknown.As insula cortex is important in emotional processing,we have examined whether the changes in synaptic plasticity in the insula cortex involved in stress resilience or vulnerability.METHODS Mice were divided into two groups:control and stress group.Stress group was treated by foot electric shock twice daily(0.8 mA,2 s,ten times in 1 min) in continuous two weeks.Then we used fear conditioning test to detect re-experiencing of traumatic experience,open field test to detect avoidance,pre-pulse inhibition experiment to detect hyper arousal.The changes of synaptic plasticity in the insular cortex were recorded by the multiple channels electrophysiology and whole cell patch.RESULTS According to the behavioral scores,it was divided into resilient and vulnerable group.In the fear conditioning test,the vulnerable group showed the significant freezing time decreased than that of the resilient group(P<0.01).In the open field test,the time that enter the center zone of vulnerable group is increased than that resilient group(P<0.01);In the pre-pulse inhibition experiment,there are not significant difference of PPI value in both groups(P=0.4239).And then electrophysiological experiments are performed to detect the synaptic plasticity of the insular cortex.Compared with the resilient group,the LTP level was decreased(P<0.05) and the mEPSC was increased(P<0.01) in vulnerable group.CONCLUSION The impairment of synaptic plasticity in the insular cortex may be one of the neural mechanisms for the vulnerability to chronic stress.展开更多
Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aime...Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aimed to compare the add-on analgesic efficacy of concentric electrode transcranial direct current stimulation (CE-tDCS) stimulation over the primary motor cortex versus the insular cortex on the management of chronic postmastectomy pain. Method: Prospective randomized double-blind sham-controlled study enrolled eighty patients with chronic postmastectomy pain that were randomly assigned to four groups: active motor (AM), sham motor (SM), active insula (AI) and sham insula (SI) group, each received 5 sessions for 20-minute duration with 2 mA tDCS over the targeted area of the contralateral side of pain. Our primary outcome was VAS score, the secondary outcomes were VDS score, LANSS score and depression symptoms by HAM-D scores, assessment was done at 4 time points (prestimulation, after 5<sup>th</sup> session, 15<sup>th</sup> day and one month after the last session). Results: Both active tDCS groups (motor and insula) showed reduction of VAS (P Conclusion: Active tDCS stimulation either targeting the primary motor cortex or the insula cortex has add-on analgesic effect for controlling neuropathic chronic post mastectomy pain and the maximum effect was at 15 days after the last session.展开更多
Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that...Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear memory.The brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear.Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory.In this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.展开更多
文摘Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.
基金supported by grants from the National Natural Science Foundation of China(32371060 and 32271065)the Lingang Laboratory(LG-QS-202203-06 and LG-QS-202203-02)the Chinese Academy of Sciences,and Benyuan Charity Foundation.
文摘The insula is a complex brain region central to the orchestration of taste perception,interoception,emotion,and decision-making.Recent research has shed light on the intricate connections between the insula and other brain regions,revealing the crucial role of this area in integrating sensory,emotional,and cognitive information.The unique anatomical position and extensive connectivity allow the insula to serve as a critical hub in the functional network of the brain.We summarize its role in interoceptive and exteroceptive sensory processing,illustrating insular function as a bridge connecting internal and external experiences.Drawing on recent research,we delineate the insular involvement in emotional processes,highlighting its implications in psychiatric conditions,such as anxiety,depression,and addiction.We further discuss the insular contributions to cognition,focusing on its significant roles in time perception and decision-making.Collectively,the evidence underscores the insular function as a dynamic interface that synthesizes diverse inputs into coherent subjective experiences and decision-making processes.Through this review,we hope to highlight the importance of the insula as an interface between sensation,emotion,and cognition,and to inspire further research into this fascinating brain region.
基金the National Natural Science Foundation of China,No.V30270502,C010703
文摘BACKGROUND： The insular cortex and habenular nucleus may be a regulatory center for obstructive sleep apnea syndrome, and dyspnea may be caused by insular cortex activity. The insular cortex is a cortical representation of obstructive sleep apnea syndrome. The habenular nucleus is a station for descending insular cortex activity. OBJECTIVE： Through actively stimulating the rat insular cortex, to observe rat respiratory movement, myoelectric activities of genioglossus, arterial partial pressure of oxygen, partial pressure of carbon dioxide and acidity-alkalinity, and to verify a hypothesis that the insular cortex is a superior-position regulation center, and the habenular nucleus is an inferior-position nervous nuclei of the insular cortex in patients with obstructive sleep apnea syndrome. DESIGN, TIME AND SETTING： The randomized, controlled animal study was performed at the Laboratory of Electrophysiology, Department of Physiology, Norman Bathune College of Medicine, Jilin University, China from September 2004 to June 2008. MATERIALS： We used L-glutamic acid （Dingguo Biological Product Research Center, Beijing, China）, lidocaine hydrochloride （Seventh Pharmacy Co., Ltd., Wuxi, China）, electric stimulator （Nihon Kohden, Japan）, and an AVL-OPTI blood gas analyzer （AVL Scientific Co., Roswell, GA, USA）. METHODS： The insular cortex of healthy adult Wistar rats underwent electrostimulation and L-glutamic acid stimulation to record changes in the myoelectric activity of genioglossus and respiratory movement. Some rats were injected with lidocaine to block the habenular nucleus before electrostimulation or L-glutamic acid stimulation. L-glutamic acid and lidocaine were injected by microelectrodes embedded in nuclear groups. MAIN OUTCOME MEASURES： Myoelectric activities of genioglossus, arterial partial pressure of oxygen, partial pressure of carbon dioxide and acidity-alkalinity were measured following apnea in rats undergoing electrostimulation in the insular cortex and following blockade of the habenular nucleus. RESULTS： Following electrostimulation and L-glutamic acid stimulation, rats developed apnea or respiratory rhythm disorders. Simultaneously, the amplitude of myoelectric activity of the genioglossus was reduced （P 〈 0.01 ）, and the electromyogram integral was decreased （P 〈 0.01）. Arterial blood gas analysis showed arterial blood acidosis, a decrease in pH （P 〈 0.05）, and an increase in the negative value of alkaline reserve （P 〈 0.01）. Lidocaine in the habenular nuclear blocked respiratory and other index changes after insular cortex stimulation. CONCLUSION： Dyspnea induced by stimulating the insular cortex may require the habenular nucleus. Paralysis of the habenular nucleus can completely eliminate insular cortex stimulation-induced dyspnea.
基金supported by the National Natural Science Foundation of China(31371120)the Foundation for Returned Overseas Students of Ministry of Education,China(HG3503)
文摘An increasing body of neuroimaging and electrophysiological studies of the brain suggest that the insular cortex（IC） integrates multimodal salient information ranging from sensation to cognitive-affective events to create conscious interoception. Especially with regard to pain experience, the IC has been supposed to participate in both sensory-discriminative and affective-motivational aspects of pain. In this review, we discuss the latest data proposing that subregions of the IC are involved in isolated pain networks： the posterior sensory circuit and the anterior emotional network. Due to abundant connections with other brain areas, the IC is likely to serve as an interface where cross-modal shaping of pain occurs. In chronic pain,however, this mode of emotional awareness and the modulation of pain are disrupted. We highlight some of the molecular mechanisms underlying the changes of the pain modulation system that contribute to the transition from acute to chronic pain in the IC.
基金This work was supported by the National Natural Science Foundation of China(32271056,81671081,and 81701095)University Science and Technology Fund Planning Projects(2022XC002 and 2019XB006).
文摘The rostral agranular insular cortex(RAIC)has been associated with pain modulation.Although the endogenous cannabinoid system(eCB)has been shown to regulate chronic pain,the roles of eCBs in the RAIC remain elusive under the neuropathic pain state.Neuropathic pain was induced in C57BL/6 mice by common peroneal nerve(CPN)ligation.The roles of the eCB were tested in the RAIC of ligated CPN C57BL/6J mice,glutamatergic,or GABAergic neuron cannabinoid receptor 1(CB1R)knockdown mice with the whole-cell patch-clamp and pain behavioral methods.The E/I ratio(amplitude ratio between mEPSCs and mIPSCs)was significantly increased in layer V pyramidal neurons of the RAIC in CPN-ligated mice.Depolarization-induced suppression of inhibition but not depolarization-induced suppression of excitation in RAIC layer V pyramidal neurons were significantly increased in CPN-ligated mice.The analgesic effect of ACEA(a CB1R agonist)was alleviated along with bilateral dorsolateral funiculus lesions,with the administration of AM251(a CB1R antagonist),and in CB1R knockdown mice in GABAergic neurons,but not glutamatergic neurons of the RAIC.Our results suggest that CB1R activation reinforces the function of the descending pain inhibitory pathway via reducing the inhibition of glutamatergic layer V neurons by GABAergic neurons in the RAIC to induce an analgesic effect in neuropathic pain.
文摘Serotonin (5HT) in the central nervous system has been associated with pain processing and modulation. The insular cortex (IC) plays an important role in the development and perception of the inflammatory and chronic pain. The role of the serotoninergic system in IC has not been completely studied. We used micro-dialysis in freely moving rats to determine the extracellular release of 5HT and its main metabolite (5HIAA) in the IC during an inflammatory process. Results showed an increase of extracellular levels of 5HT and 5HIAA in the IC during carrageenan-induced inflammation and this augmentation correlates with a decrease of behavioral mechanonociceptive response. Furthermore, the exogenous administration of 5HT and 5HIAA in the IC increases the nociceptive response. Our current data imply that the serotoninergic system in the IC participates in the long-term pain process.
基金National Natural Science Foundation of China(81402912).
文摘OBJECTIVE Exposure to stressful events can be differently perceived by individuals depending on the level of stress resilience or vulnerability.The neural processes that underlie such clinical y and social y important differences are largely unknown.As insula cortex is important in emotional processing,we have examined whether the changes in synaptic plasticity in the insula cortex involved in stress resilience or vulnerability.METHODS Mice were divided into two groups:control and stress group.Stress group was treated by foot electric shock twice daily(0.8 mA,2 s,ten times in 1 min) in continuous two weeks.Then we used fear conditioning test to detect re-experiencing of traumatic experience,open field test to detect avoidance,pre-pulse inhibition experiment to detect hyper arousal.The changes of synaptic plasticity in the insular cortex were recorded by the multiple channels electrophysiology and whole cell patch.RESULTS According to the behavioral scores,it was divided into resilient and vulnerable group.In the fear conditioning test,the vulnerable group showed the significant freezing time decreased than that of the resilient group(P<0.01).In the open field test,the time that enter the center zone of vulnerable group is increased than that resilient group(P<0.01);In the pre-pulse inhibition experiment,there are not significant difference of PPI value in both groups(P=0.4239).And then electrophysiological experiments are performed to detect the synaptic plasticity of the insular cortex.Compared with the resilient group,the LTP level was decreased(P<0.05) and the mEPSC was increased(P<0.01) in vulnerable group.CONCLUSION The impairment of synaptic plasticity in the insular cortex may be one of the neural mechanisms for the vulnerability to chronic stress.
文摘Background: Transcranial direct current stimulation (tDCS) across cortical brain areas appears to improve various forms of pain, yet evidence of tDCS efficiency and ideal stimulation target is lacking. This study aimed to compare the add-on analgesic efficacy of concentric electrode transcranial direct current stimulation (CE-tDCS) stimulation over the primary motor cortex versus the insular cortex on the management of chronic postmastectomy pain. Method: Prospective randomized double-blind sham-controlled study enrolled eighty patients with chronic postmastectomy pain that were randomly assigned to four groups: active motor (AM), sham motor (SM), active insula (AI) and sham insula (SI) group, each received 5 sessions for 20-minute duration with 2 mA tDCS over the targeted area of the contralateral side of pain. Our primary outcome was VAS score, the secondary outcomes were VDS score, LANSS score and depression symptoms by HAM-D scores, assessment was done at 4 time points (prestimulation, after 5<sup>th</sup> session, 15<sup>th</sup> day and one month after the last session). Results: Both active tDCS groups (motor and insula) showed reduction of VAS (P Conclusion: Active tDCS stimulation either targeting the primary motor cortex or the insula cortex has add-on analgesic effect for controlling neuropathic chronic post mastectomy pain and the maximum effect was at 15 days after the last session.
基金supported by grants from the STI2030-Major Projects(2021ZD0202800)the National Natural Science Foundation of China(32071023 and 32371078)+2 种基金the Program of Shanghai Academic/Technology Research Leader(22XD1420700)the Shanghai Municipal Health Commission(2022XD046)Innovative Research Team of High-Level Local Universities in Shanghai.
文摘Fear extinction is a biological process in which learned fear behavior diminishes without anticipated reinforcement,allowing the organism to re-adapt to ever-changing situations.Based on the behavioral hypothesis that extinction is new learning and forms an extinction memory,this new memory is more readily forgettable than the original fear memory.The brain’s cellular and synaptic traces underpinning this inherently fragile yet reinforceable extinction memory remain unclear.Intriguing questions are about the whereabouts of the engram neurons that emerged during extinction learning and how they constitute a dynamically evolving functional construct that works in concert to store and express the extinction memory.In this review,we discuss recent advances in the engram circuits and their neural connectivity plasticity for fear extinction,aiming to establish a conceptual framework for understanding the dynamic competition between fear and extinction memories in adaptive control of conditioned fear responses.
