Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of sufferin...Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.展开更多
Objective To investigate the gustatory neural response of the neurons to five basic taste stimuli in the parabrachial nucleus (PBN). Methods Evoked responses from PBN taste neurons to tastants were recorded using st...Objective To investigate the gustatory neural response of the neurons to five basic taste stimuli in the parabrachial nucleus (PBN). Methods Evoked responses from PBN taste neurons to tastants were recorded using standard extracellular microelectrode technique. Results 46 taste neurons were recorded in PBN, and most of them were broadly responsive. On the basis of their most effective taste stimuli, these taste neurons were classified into five types. Those are NaCl-, HCl-, quinine-, sucrose-, and monosodium glutamate (MSG)-best neurons. Except for the quinine-best neurons, the responses of each best-stimulus category to its best stimulus were significantly stronger than those of others (P<0.01). The results of correlation analysis showed that the correlations between sucrose and each of the other 4 tastants were smaller than those among others. Conclusion The results suggest that PBN taste neurons probably play an important role in discriminating for hedonic taste.展开更多
This study examined the stimulus specificity of external lateral parabrachial (LPBe) rewarding stimulation by using two identical learning procedures that may dissociate conditioned reinforcement to either the place o...This study examined the stimulus specificity of external lateral parabrachial (LPBe) rewarding stimulation by using two identical learning procedures that may dissociate conditioned reinforcement to either the place or the flavor stimulus. Animals were presented with two distinct flavors in two different positions (left and right) that were varied throughout the experimental sessions. In the first experiment, LPBe stimulation was associated with one or other flavor, while in the second it was conditioned to one or other place in which these flavors were offered. The results show that, despite stimulus interferences, the animals develop specific conditioned preferences for the flavor stimuli (experiment 2A), and also for the place of their presentation (experiment 2B). These data are discussed in the context of brain reward systems and the biological constraints that characterize some learning modalities.展开更多
Pre-and neonatal fasting in the rat has been used as an experimental model to obtain information on how the newborn gustatory system can be damaged, in- terfering with the basic sensory and hedonic proc- esses to diff...Pre-and neonatal fasting in the rat has been used as an experimental model to obtain information on how the newborn gustatory system can be damaged, in- terfering with the basic sensory and hedonic proc- esses to different tastants. Fasting during the prenatal period and for 24 days postnatally results in signifi- cant reductions of body and brain weight, number of branches, dendritic density, and cross-sectional area of the PBN multipolar neurons in the central lateral and central medial subnucleus particularly at post- natal days 20 and 30. Furthermore, the underfeeding paradigm affected more the middle portions of the dendritic tree than other parts of the neurons possibly disturbing the afferent characteristics of neuronal acti- vity propagation that may partly disrupt the elabora- tion of synaptic plasticity at later ages. These findings may play a role in the development of complex physio- logical phenomena such as food intake, taste discrimi- nation, learning taste aversion, and appetitive beha- vior.展开更多
Aim:Sleep disorders are common in Alzheimer’s disease(AD)and assumed to directly influence cognitive function and progression of the disease.The present study evaluated sleep characteristics in a rat model of AD that...Aim:Sleep disorders are common in Alzheimer’s disease(AD)and assumed to directly influence cognitive function and progression of the disease.The present study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular administration of streptozocin,and we assessed the possible underlying mechanisms.Methods:The cognition ability of rats was assessed by Morris water maze(MWM)trails.Sleep parameters were analyzed by electroencephalographic(EEG)and electromyographic(EMG)recordings.The neuronal activity in sleep-wake regulating brain areas was evaluated by double-staining immunohistochemistry test.High performance liquid chromatograph-electrochemical detection(HPLC-ECD)was used for the detection of neurotransmitters.Results:On day 14 after STZ injection,the rats exhibited sleep disorders that are similar to those in AD patients as evidenced by significant increase in wakefulness and decrease in rapid-eye movement sleep(REMS)and non-REMS.The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ rats.In the ventrolateral preoptic nucleus(VLPO),the activity ofγ-aminobutyric acid(GABA)neurons was suppressed.In the arousal-driving parabrachial nucleus(PBN),GABAergic activity was suppressed,whereas glutamatergic activity was promoted.The neurotransmitter analysis revealed a reduction of GABA in the VLPO and PBN and elevations of glutamate in the PBN.A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar sleep disorder pattern as in STZ rats.Furthermore,a microinjection of GABA in the PBN improved sleep disorders induced by STZ.Conclusion:These results suggest that the reduction of GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders induced by STZ.Our novel findings encourage further study aimed at investigating the new mechanisms of sleep regulation in sporadic AD.展开更多
The lateral parabrachial nucleus(PBL)is implicated in the regulation of respiratory activity.Sodium leak channel(NALCN)mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and ...The lateral parabrachial nucleus(PBL)is implicated in the regulation of respiratory activity.Sodium leak channel(NALCN)mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans.Here,we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia.Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency(RF)in mice;whereas chemogenetic inhibition suppressed RF.NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia.NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine.Under sevoflurane anesthesia,painful stimuli rapidly increased the RF,which was not affected by NALCN knockdown in PBL glutamatergic neurons.This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.展开更多
The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural ci...The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons comprise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.展开更多
Studies have shown that there are strong interactions between gustatory and visceral sensations the central nervous system when rats ingest sweet foods or solutions. To investigate the role of th subdiaphragmatic vagi...Studies have shown that there are strong interactions between gustatory and visceral sensations the central nervous system when rats ingest sweet foods or solutions. To investigate the role of th subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats depriv~ of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water II E展开更多
The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to...The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.展开更多
To examine whether the activation of brainstem neurons during intake of a sweet tastant is due to orosensory signals or post-ingestive factors,we compared the distribution of c-Fos-like immunoreactivity(c-FLI)in the n...To examine whether the activation of brainstem neurons during intake of a sweet tastant is due to orosensory signals or post-ingestive factors,we compared the distribution of c-Fos-like immunoreactivity(c-FLI)in the nucleus of the solitary tract(NST)and parabrachial nucleus(PBN)of brainstem following ingestion of 0.25 M sucrose or 0.005 M saccharin solutions.Immunopositive neurons were localized mainly in the middle zone of the PBN and four rostral-caudal subregions of the NST.Intake of sucrose increased the number of FLI neurons in almost every subnucleus of the PBN(F_((2,13))=7.610,P=0.023),in addition to the caudal NST at the level of the area postrema(F_((2,13))=10.777,P=0.003)and the NST intermediate zone(F_((2,13))=7.193,P=0.014).No significant increase in the number of c-Fos positive neurons was detected in response to saccharin ingestion,although there was a trend towards a modest increase in a few select NST and PBN nuclei.These results suggest that the PBN and NST may be involved in sweet taste perception and modulation of sweet tastant intake,but the significantly enhanced intensity of Fos expression induced by sucrose indicates that PBN/NST neuronal activity is driven by the integrated effects of sweet taste sensation and post-ingestive signals.展开更多
基金supported by the Shenzhen Key Laboratory of Drug Addiction (ZDSYS20190902093601675)CAS Key Laboratory of Brain Connectome and Manipulation (2019DP173024)+2 种基金National Natural Science Foundation of China (82274358)Shenzhen-Hong Kong Institute of Brain ScienceGuangdong Basic and Applied Basic Research Foundation (2023B1515040009)
文摘Painful stimuli elicit first-line reflexive defensive reactions and,in many cases,also evoke second-line recuperative behaviors,the latter of which reflects the sensing of tissue damage and the alleviation of suffering.The lateral parabrachial nucleus(lPBN),composed of external-(elPBN),dorsal-(dlPBN),and central/superior-subnuclei(jointly referred to as slPBN),receives sensory inputs from spinal projection neurons and plays important roles in processing affective information from external threats and body integrity disruption.However,the organizational rules of lPBN neurons that provoke diverse behaviors in response to different painful stimuli from cutaneous and deep tissues remain unclear.In this study,we used region-specific neuronal depletion or silencing approaches combined with a battery of behavioral assays to show that slPBN neurons expressing substance P receptor(NK1R)(lPBNNK1R)are crucial for driving pain-associated self-care behaviors evoked by sustained noxious thermal and mechanical stimuli applied to skin or bone/muscle,while elPBN neurons are dispensable for driving such reactions.Notably,lPBNNK1R neurons are specifically required for forming sustained somatic pain-induced negative teaching signals and aversive memory but are not necessary for fear-learning or escape behaviors elicited by external threats.Lastly,both lPBNNK1R and elPBN neurons contribute to chemical irritant-induced nocifensive reactions.Our results reveal the functional organization of parabrachial substrates that drive distinct behavioral outcomes in response to sustained pain versus external danger under physiological conditions.
基金ThisresearchwassupportedbytheNationalNaturalScienceFoundationofChina (No .39870 2 71)
文摘Objective To investigate the gustatory neural response of the neurons to five basic taste stimuli in the parabrachial nucleus (PBN). Methods Evoked responses from PBN taste neurons to tastants were recorded using standard extracellular microelectrode technique. Results 46 taste neurons were recorded in PBN, and most of them were broadly responsive. On the basis of their most effective taste stimuli, these taste neurons were classified into five types. Those are NaCl-, HCl-, quinine-, sucrose-, and monosodium glutamate (MSG)-best neurons. Except for the quinine-best neurons, the responses of each best-stimulus category to its best stimulus were significantly stronger than those of others (P<0.01). The results of correlation analysis showed that the correlations between sucrose and each of the other 4 tastants were smaller than those among others. Conclusion The results suggest that PBN taste neurons probably play an important role in discriminating for hedonic taste.
文摘This study examined the stimulus specificity of external lateral parabrachial (LPBe) rewarding stimulation by using two identical learning procedures that may dissociate conditioned reinforcement to either the place or the flavor stimulus. Animals were presented with two distinct flavors in two different positions (left and right) that were varied throughout the experimental sessions. In the first experiment, LPBe stimulation was associated with one or other flavor, while in the second it was conditioned to one or other place in which these flavors were offered. The results show that, despite stimulus interferences, the animals develop specific conditioned preferences for the flavor stimuli (experiment 2A), and also for the place of their presentation (experiment 2B). These data are discussed in the context of brain reward systems and the biological constraints that characterize some learning modalities.
文摘Pre-and neonatal fasting in the rat has been used as an experimental model to obtain information on how the newborn gustatory system can be damaged, in- terfering with the basic sensory and hedonic proc- esses to different tastants. Fasting during the prenatal period and for 24 days postnatally results in signifi- cant reductions of body and brain weight, number of branches, dendritic density, and cross-sectional area of the PBN multipolar neurons in the central lateral and central medial subnucleus particularly at post- natal days 20 and 30. Furthermore, the underfeeding paradigm affected more the middle portions of the dendritic tree than other parts of the neurons possibly disturbing the afferent characteristics of neuronal acti- vity propagation that may partly disrupt the elabora- tion of synaptic plasticity at later ages. These findings may play a role in the development of complex physio- logical phenomena such as food intake, taste discrimi- nation, learning taste aversion, and appetitive beha- vior.
文摘Aim:Sleep disorders are common in Alzheimer’s disease(AD)and assumed to directly influence cognitive function and progression of the disease.The present study evaluated sleep characteristics in a rat model of AD that was induced by intracerebroventricular administration of streptozocin,and we assessed the possible underlying mechanisms.Methods:The cognition ability of rats was assessed by Morris water maze(MWM)trails.Sleep parameters were analyzed by electroencephalographic(EEG)and electromyographic(EMG)recordings.The neuronal activity in sleep-wake regulating brain areas was evaluated by double-staining immunohistochemistry test.High performance liquid chromatograph-electrochemical detection(HPLC-ECD)was used for the detection of neurotransmitters.Results:On day 14 after STZ injection,the rats exhibited sleep disorders that are similar to those in AD patients as evidenced by significant increase in wakefulness and decrease in rapid-eye movement sleep(REMS)and non-REMS.The c-Fos expression analysis indicated that neuronal activity and the number of neurons in the dorsal raphe nucleus and locus coeruleus decreased in STZ rats.In the ventrolateral preoptic nucleus(VLPO),the activity ofγ-aminobutyric acid(GABA)neurons was suppressed.In the arousal-driving parabrachial nucleus(PBN),GABAergic activity was suppressed,whereas glutamatergic activity was promoted.The neurotransmitter analysis revealed a reduction of GABA in the VLPO and PBN and elevations of glutamate in the PBN.A direct injection of the GABAA receptor antagonist bicuculline in the PBN in normal rats induced a similar sleep disorder pattern as in STZ rats.Furthermore,a microinjection of GABA in the PBN improved sleep disorders induced by STZ.Conclusion:These results suggest that the reduction of GABAergic inhibition in the PBN and VLPO may be involved in sleep disorders induced by STZ.Our novel findings encourage further study aimed at investigating the new mechanisms of sleep regulation in sporadic AD.
基金supported by the National Natural Science Foundation of China(82271290 and 82301403)the Natural Science Foundation of Sichuan Province(2022NSFSC1399)+1 种基金the Health Commission of Sichuan Province(21PJ014)the Key R&D(Major Science and Technology Project)of the Sichuan Science and Technology Department(2023YFS0138 and 2023ZYD0168).
文摘The lateral parabrachial nucleus(PBL)is implicated in the regulation of respiratory activity.Sodium leak channel(NALCN)mutations disrupt the respiratory rhythm and influence anesthetic sensitivity in both rodents and humans.Here,we investigated whether the NALCN in PBL glutamatergic neurons maintains respiratory function under general anesthesia.Our results showed that chemogenetic activation of PBL glutamatergic neurons increased the respiratory frequency(RF)in mice;whereas chemogenetic inhibition suppressed RF.NALCN knockdown in PBL glutamatergic neurons but not GABAergic neurons significantly reduced RF under physiological conditions and caused more respiratory suppression under sevoflurane anesthesia.NALCN knockdown in PBL glutamatergic neurons did not further exacerbate the respiratory suppression induced by propofol or morphine.Under sevoflurane anesthesia,painful stimuli rapidly increased the RF,which was not affected by NALCN knockdown in PBL glutamatergic neurons.This study suggested that the NALCN is a key ion channel in PBL glutamatergic neurons that maintains respiratory frequency under volatile anesthetic sevoflurane but not intravenous anesthetic propofol.
基金supported by the University of Michigan startup funds and the NIH Grants R01 AT011652 and R01 HL156989.
文摘The parabrachial nucleus(PBN)integrates interoceptive and exteroceptive information to control various behavioral and physiological processes including breathing,emotion,and sleep/wake regulation through the neural circuits that connect to the forebrain and the brainstem.However,the precise identity and function of distinct PBN subpopulations are still largely unknown.Here,we leveraged molecular characterization,retrograde tracing,optogenetics,chemogenetics,and electrocortical recording approaches to identify a small subpopulation of neurotensin-expressing neurons in the PBN that largely project to the emotional control regions in the forebrain,rather than the medulla.Their activation induces freezing and anxiety-like behaviors,which in turn result in tachypnea.In addition,optogenetic and chemogenetic manipulations of these neurons revealed their function in promoting wakefulness and maintaining sleep architecture.We propose that these neurons comprise a PBN subpopulation with specific gene expression,connectivity,and function,which play essential roles in behavioral and physiological regulation.
基金financially supported by the National Natural Science Foundation of China, No. 81071029the Joint Funds of the Natural Science Foundation Committee with Henan Province Government for Fostering Talents, No. U1204809
文摘Studies have shown that there are strong interactions between gustatory and visceral sensations the central nervous system when rats ingest sweet foods or solutions. To investigate the role of th subdiaphragmatic vagi in transmitting general visceral information during the process of drinking sweet-tasting solutions, we examined the effects of subdiaphragmatic vagotomy on the intake of 0.5 mol/L sucrose, 0.005 mol/L saccharin or distilled water over the course of 1 hour in rats depriv~ of water. Results showed no significant difference in consumption of these three solutions in vagotomized rats. However, rats in the sham-surgery group drank more saccharin solution than sucrose solution or distilled water. Moreover, the intake of distilled water was similar between vagotomized rats and sham-surgery group rats, but significantly less sucrose and saccharin were consumed by vagotomized rats compared with rats in the sham-surgery group. These findings indicate that subdiaphragmatic vagotomy reduces intake of sweet-tasting solution in rats, and suggest that vagal and extravagal inputs play a balanced role in the control of the intake of sweet-tasting solutions. They also suggest that subdiaphragmatic vagotomy eliminates the difference in hedonic perception induced by sweet-tasting solutions compared with distilled water II E
文摘The perception of pain involves the activation of the spinal pathway as well as the supra-spinal pathway,which targets brain regions involved in affective and cognitive processes.Pain and emotions have the capacity to influence each other reciprocally;negative emotions,such as depression and anxiety,increase the risk for chronic pain,which may lead to anxiety and depression.The amygdala is a key-player in the expression of emotions,receives direct nociceptive information from the parabrachial nucleus,and is densely innervated by noradrenergic brain centers.In recent years,the amygdala has attracted increasing interest for its role in pain perception and modulation.In this review,we will give a short overview of structures involved in the pain pathway,zoom in to afferent and efferent connections to and from the amygdala,with emphasis on the direct parabrachio-amygdaloid pathway and discuss the evidence for amygdala’s role in pain processing and modulation.In addition to the involvement of the amygdala in negative emotions during the perception of pain,this brain structure is also a target site for many neuromodulators to regulate the perception of pain.We will end this article with a short review on the effects of noradrenaline and its role in hypoalgesia and analgesia.
基金supported by the National Natural Science Foundation of China(No.30970973)and the Fundamental Research Funds for the Central Universities.
文摘To examine whether the activation of brainstem neurons during intake of a sweet tastant is due to orosensory signals or post-ingestive factors,we compared the distribution of c-Fos-like immunoreactivity(c-FLI)in the nucleus of the solitary tract(NST)and parabrachial nucleus(PBN)of brainstem following ingestion of 0.25 M sucrose or 0.005 M saccharin solutions.Immunopositive neurons were localized mainly in the middle zone of the PBN and four rostral-caudal subregions of the NST.Intake of sucrose increased the number of FLI neurons in almost every subnucleus of the PBN(F_((2,13))=7.610,P=0.023),in addition to the caudal NST at the level of the area postrema(F_((2,13))=10.777,P=0.003)and the NST intermediate zone(F_((2,13))=7.193,P=0.014).No significant increase in the number of c-Fos positive neurons was detected in response to saccharin ingestion,although there was a trend towards a modest increase in a few select NST and PBN nuclei.These results suggest that the PBN and NST may be involved in sweet taste perception and modulation of sweet tastant intake,but the significantly enhanced intensity of Fos expression induced by sucrose indicates that PBN/NST neuronal activity is driven by the integrated effects of sweet taste sensation and post-ingestive signals.
