The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional informat...The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.展开更多
The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this class...The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the wholecell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns： sustained-regular（n = 4） and sustained-adapting firing patterns（n = 3）. The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies.展开更多
Growing evidence has been found to suggest that early development of the central auditory system is dependent on acoustic stimuli. Peripheral damage caused by noise exposure and ototoxic drugs can induce functional an...Growing evidence has been found to suggest that early development of the central auditory system is dependent on acoustic stimuli. Peripheral damage caused by noise exposure and ototoxic drugs can induce functional and anatomical changes along the auditory pathways. The inferior colliculus (IC) is a unique structure in the auditory system located between the primary auditory nuclei of the brainstem and the thala-mus. Damage to the IC inhibitory circuitry may affect central auditory processing and sound perception. Here, we review some of the striking electrophysiological changes in the IC that occur after noise exposure and ototoxic drug treatment. A common occurrence that emerges in the IC after peripheral damage is hyper-excitability of sound-evoked response. The hyperexcitability of the IC is likely related with reduced inhibi-tory response that requires normal peripheral inputs. Early age hearing loss can result in a long lasting in-creased susceptibility to audiogenic seizure which is related to hyperactivity in the IC evoked by loud sounds. Our studies suggest that hearing loss can cause increased IC neuron responsiveness which may be related to tinnitus, hyperacusis, and audiogenic seizure.展开更多
AIM： To determine if brain-derived neurotrophic factor （BDNF） could offer protention to retinal ganglion cells following a superior colliculus （SC） lesion in mice using pattern electroretinogram （PERG） and opti...AIM： To determine if brain-derived neurotrophic factor （BDNF） could offer protention to retinal ganglion cells following a superior colliculus （SC） lesion in mice using pattern electroretinogram （PERG） and optical coherence tomography （OCT） as a measures of ganglion cell response and retinal health. METHODS： Seven C57BIJ6J mice with BDNF protection were tested with PERG and OCT before and after SC lesions, RESULTS： Compared with baseline PERG, the amplitude of PERG decreased 11.7% after SC lesions, but not significantly（P〉0.05）. Through fast Fourier transform （FFT） analysis of the PERGs before and after SC lesions, it was found that dominant frequency of PERGs stayed unchanged, suggesting that the ganglion cells of the retina remained relatively healthy inspite of damage to the ends of the ganglion cell axons. Also, OCT showed no changes in retinal thickness after lesions. CONCLUSION： It was concluded that BDNF is essential component of normal retinal and helps retina keeping normal function. While retina lack of BDNF, ex vivo resource of BDNF provides protection to the sick retina. It implies that BDNF is a kind therapeutic neurotrophic factor to retina neurodegeneration diseases, such as glaucoma, age related macular degeneration.展开更多
Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn- drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product F...Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn- drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor- mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound （hyperacusis）. The molecular basis of fragile X syndrome is thoroughly understood; however, the neural mechanisms underly- ing hyperacusis have not yet been determined. As the inferior colliculus （IC） is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob- served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.展开更多
Duration is a salient feature of acoustic signals including speech. Duration tuning was first reported in frogs and later in echolocating bats. More recently, duration tuning has been reported in non-echolocating mamm...Duration is a salient feature of acoustic signals including speech. Duration tuning was first reported in frogs and later in echolocating bats. More recently, duration tuning has been reported in non-echolocating mammals and appears to be a fundamental encoding mechanism throughout the animal kingdom. However, the duration tuning reported in these non-echolocating mammals appears to be much weaker than that in the previous studies on bats. In contrast to this finding, our recent study reported that duration tuning in the IC in guinea pigs appeared to be strong when it was measured using an appropriate temporal window. With such a temporal window, duration tuning was found to be compatible with that of echo-locating bats. In the present report, we further demonstrate that duration tuning in the IC of this species is established by interaction between excitation and GABAergic inhibition. In addition to overall increase in responsiveness, application of bicuculline(BIC), a GABA-A receptor antagonist, was found to significantly reduce or eliminate duration selectivity in 44 out of the 67 neurons that showed clear duration tuning from a sample of 340 neurons.展开更多
The superior colliculus (SC) is a laminated midbrain structure responsible for visual orientation behaviors. In the mature SC, neurons in the stratum griseum superficiale (SGS) receive visual inputs that contribute to...The superior colliculus (SC) is a laminated midbrain structure responsible for visual orientation behaviors. In the mature SC, neurons in the stratum griseum superficiale (SGS) receive visual inputs that contribute to exciting premotor neurons in the stratum griseum intermediale (SGI) through a dorsoventral pathway. SGI activation generates feedback signals to the SGS through a ventrodorsal pathway. However, the developmental changes in signal transmission within the SC around the time of eye opening are not yet well understood. We compared the functional connections between the SGS and SGI before and after eye opening by imaging the neuronal population responses using a voltage-sensitive absorption dye in mouse SC slices. Electrophoresis of a fluorescent dye from the stimulating electrodes was used to fill the cells in the stimulated site. We here show that the dorsoventral transmission is present both before and after eye opening. This is in contrast to our previous finding that the ventrodorsal transmission develops after eye opening. Functions of intrinsic inhibitory systems mediated by gamma-aminobutyric acid were also investigated with the antagonist. The processes stained by electrophoresis from stimulating electrodes before eye opening were confined within the respective stimulated layers. Whereas, after eye opening, the processes were widely extended especially dorsoventrally and ventrodorsally invading the SGI and SGS, respectively. These corresponded well to the early component of voltage responses that is known to reflect the activation of presynaptic elements, presumably the axonal arborizations and varicosities. Thus, the optically-revealed functional connections between the SGS and SGI were correlated to the morphology.展开更多
Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA r...Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.展开更多
The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across ...The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.展开更多
Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have b...Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12(P12), which is earlier than in the dLGN(P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.展开更多
Neurons in superficial layers of the superior colliculus of the rabbit are classified into three types by their electrophysiological properties. Among them, two types belong to projecting neurons which send axons to t...Neurons in superficial layers of the superior colliculus of the rabbit are classified into three types by their electrophysiological properties. Among them, two types belong to projecting neurons which send axons to the thalamic pulvinar (N=52) and dorsal lateral geniculate nucleus (N = 54) respectively. All other neurons are pooled into the third type (N=99). Projecting neurons of both types receive monosynaptic visual inputs via optic tract fibers of similar conduction velocity, indicating that in the superior colliculus of the rabbit, there is no difference in conduction velocity between the two pathways. They also receive trisynaptic inhibitory inputs, most likely via recurrent inhibitory circuits. The third type of neurons receives disynaptic optic and trisynaptic inhibitory inputs. The function of neurons of the third type is studied.展开更多
Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prer...Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.展开更多
The neural modulation in central auditory system plays an important role in perception and processing of sound signal and auditory cognition.The inferior colliculus(IC)is both a relay station in central auditory pathw...The neural modulation in central auditory system plays an important role in perception and processing of sound signal and auditory cognition.The inferior colliculus(IC)is both a relay station in central auditory pathway and a sub-cortical auditory center doing the sound signal processing.IC is also modulated by the descending projections from the cortex and auditory thalamus,medial geniculate body,and these neural modulations not only can affect ongoing sound signal processing but can also induce plastic changes in IC.展开更多
In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be di...In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.展开更多
Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients...Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.展开更多
Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the n...Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.展开更多
Adult guinea pigs with normal Preyer’s reflexes were used in this experiment and were di-vided into 3 groups according to the intensity of noise and exposure time.Auditory brainstemevoked response was recorded before...Adult guinea pigs with normal Preyer’s reflexes were used in this experiment and were di-vided into 3 groups according to the intensity of noise and exposure time.Auditory brainstemevoked response was recorded before and after exposure to noise.Clicks were presented monaurallyat a rate of high (50Hz) as well as low (10Hz).The superior olive and inferior colliculus were ob-served under an electron microscope after the guinea pigs were exposured to 110dB noise for30min.The average shift of wave Ⅳ amplitude-intensity function curve was more than that ofwave Ⅰ after exposure to intensive noise.The difference value of wave \ latency from low(10Hz) to high (50Hz) stimulus click rate decreased and was negatively correlated with the exposuretime.Ⅰ-Ⅴ,Ⅲ-Ⅴ and Ⅳ-Ⅴ interpeak latencies were shorter after exposure to noise.Themitochondria and neurilemma swelling were found in the superior olive and inferior colliculus afterexposure,Some mechanisms of the changes of auditory center were discussed in this paper.展开更多
Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the r...Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.展开更多
In order to explore the possible mechanism of corticofugal modulation of excitatory frequency tuning curves (EFTCs) of midbrain neurons, we examined the change of sharpness, frequency-intensity response area, minimum ...In order to explore the possible mechanism of corticofugal modulation of excitatory frequency tuning curves (EFTCs) of midbrain neurons, we examined the change of sharpness, frequency-intensity response area, minimum threshold of both EFTCs and inhibitory frequency tuning curves (IFTCs) of inferior collicular neurons during corticofugal modulation using two-tone inhibition paradigm and micro-electrical stimulation technique. Our data showed that corticofugal inhibition increased sharpness, minimum threshold, and decreased the frequency-intensity response area of EFTCs, at the same time it decreased the sharpness, minimum threshold but increased the frequency-intensity response area of IFTCs. The opposite results were observed for EFTCs and IFTCs of corticofugally facilitated inferior collicular neurons. During corticofugal inhibition, the percent change of frequency-intensity response area of EFTCs had significant correlation with the percent change of that of IFTCs. These data suggest that cortical展开更多
基金supported by the National Natural Science Foundation of China,No.81271090 and the Beijing Natural Science Foundation,No.7112055
文摘The precedence effect is a prerequisite for faithful sound localization in a complex auditory environment, and is a physiological phenomenon in which the auditory system selectively suppresses the directional information from echoes. Here we investigated how neurons in the inferior colliculus respond to the paired sounds that produce precedence-effect illusions, and whether their firing behavior can be modulated through inhibition with gamma-aminobutyric acid （GABA）. We recorded extracellularly from 36 neurons in rat inferior colliculus under three conditions： no injection, injection with saline, and injection with gamma-aminobutyric acid. The paired sounds that produced precedence effects were two identical 4-ms noise bursts, which were delivered contralaterally or ipsilaterally to the recording site. The normalized neural responses were measured as a function of different inter-stimulus delays and half-maximal interstimulus delays were acquired. Neuronal responses to the lagging sounds were weak when the inter-stimulus delay was short, but increased gradually as the delay was lengthened. Saline injection produced no changes in neural responses, but after local gamma-arninobutyric acid application, responses to the lagging stimulus were suppressed. Application of gamma-aminobutyric acid affected the normalized response to lagging sounds, independently of whether they or the paired sounds were contralateral or ipsilateral to the recording site. These observations suggest that local inhibition by gamma-aminobutyric acid in the rat inferior colliculus shapes the neural responses to lagging sounds, and modulates the precedence effect.
基金supported by the National Natural Science Foundation of China,No.81271090
文摘The γ-aminobutyric acid neurons（GABAergic neurons） in the inferior colliculus are classified into various patterns based on their intrinsic electrical properties to a constant current injection. Although this classification is associated with physiological function, the exact role for neurons with various firing patterns in acoustic processing remains poorly understood. In the present study, we analyzed characteristics of inferior colliculus neurons in vitro, and recorded responses to stimulation of the dorsal nucleus of the lateral lemniscus using the wholecell patch clamp technique. Seven inferior colliculus neurons were tested and were classified into two firing patterns： sustained-regular（n = 4） and sustained-adapting firing patterns（n = 3）. The majority of inferior colliculus neurons exhibited slight changes in response to stimulation and bicuculline. The responses of one neuron with a sustained-adapting firing pattern were suppressed after stimulation, but recovered to normal levels following application of the γ-aminobutyric acid receptor antagonist. One neuron with a sustained-regular pattern showed suppressed stimulation responses, which were not affected by bicuculline. Results suggest that GABAergic neurons in the inferior colliculus exhibit sustained-regular or sustained-adapting firing patterns. Additionally, GABAergic projections from the dorsal nucleus of the lateral lemniscus to the inferior colliculus are associated with sound localization. The different neuronal responses of various firing patterns suggest a role in sound localization. A better understanding of these mechanisms and functions will provide better clinical treatment paradigms for hearing deficiencies.
基金supported by Royal National Institute for Deaf People
文摘Growing evidence has been found to suggest that early development of the central auditory system is dependent on acoustic stimuli. Peripheral damage caused by noise exposure and ototoxic drugs can induce functional and anatomical changes along the auditory pathways. The inferior colliculus (IC) is a unique structure in the auditory system located between the primary auditory nuclei of the brainstem and the thala-mus. Damage to the IC inhibitory circuitry may affect central auditory processing and sound perception. Here, we review some of the striking electrophysiological changes in the IC that occur after noise exposure and ototoxic drug treatment. A common occurrence that emerges in the IC after peripheral damage is hyper-excitability of sound-evoked response. The hyperexcitability of the IC is likely related with reduced inhibi-tory response that requires normal peripheral inputs. Early age hearing loss can result in a long lasting in-creased susceptibility to audiogenic seizure which is related to hyperactivity in the IC evoked by loud sounds. Our studies suggest that hearing loss can cause increased IC neuron responsiveness which may be related to tinnitus, hyperacusis, and audiogenic seizure.
文摘AIM： To determine if brain-derived neurotrophic factor （BDNF） could offer protention to retinal ganglion cells following a superior colliculus （SC） lesion in mice using pattern electroretinogram （PERG） and optical coherence tomography （OCT） as a measures of ganglion cell response and retinal health. METHODS： Seven C57BIJ6J mice with BDNF protection were tested with PERG and OCT before and after SC lesions, RESULTS： Compared with baseline PERG, the amplitude of PERG decreased 11.7% after SC lesions, but not significantly（P〉0.05）. Through fast Fourier transform （FFT） analysis of the PERGs before and after SC lesions, it was found that dominant frequency of PERGs stayed unchanged, suggesting that the ganglion cells of the retina remained relatively healthy inspite of damage to the ends of the ganglion cell axons. Also, OCT showed no changes in retinal thickness after lesions. CONCLUSION： It was concluded that BDNF is essential component of normal retinal and helps retina keeping normal function. While retina lack of BDNF, ex vivo resource of BDNF provides protection to the sick retina. It implies that BDNF is a kind therapeutic neurotrophic factor to retina neurodegeneration diseases, such as glaucoma, age related macular degeneration.
文摘Fragile X syndrome is the most common form of inherited mental retardation affecting up to 1 in 4000 individuals. The syn- drome is induced by a mutation in the FMR1 gene, causing a deficiency in its gene by-product FMRP. Impairment in the nor- mal functioning of FMRP leads to learning and memory deficits and heightened sensitivity to sensory stimuli, including sound （hyperacusis）. The molecular basis of fragile X syndrome is thoroughly understood; however, the neural mechanisms underly- ing hyperacusis have not yet been determined. As the inferior colliculus （IC） is the principal midbrain nucleus of the auditory pathway, the current study addresses the questions underlying the neural mechanism of hyperacusis within the IC of fragile X mice. Acute experiments were performed in which electrophysiological recordings of the IC in FMR1-KO and WT mice were measured. Results showed that Q-values for WT were significantly larger than that of FMR-1 KO mice, indicating that WT mice exhibit sharper tuning curves than FMR1-KO mice. We also found the ratio of the monotonic neurons in the KO mice was much higher than the WT mice. These results suggest that lack of FMRP in the auditory system affects the developmental maturation and function of structures within the auditory pathway, and in this case specifically the IC. The dysfunction ob- served within the auditory neural pathway and in particular the IC may be related to the increased susceptibility to sound as seen in individuals with fragile X syndrome. Our study may help on understanding the mechanisms of the fragile X syndrome and hyperacusis.
文摘Duration is a salient feature of acoustic signals including speech. Duration tuning was first reported in frogs and later in echolocating bats. More recently, duration tuning has been reported in non-echolocating mammals and appears to be a fundamental encoding mechanism throughout the animal kingdom. However, the duration tuning reported in these non-echolocating mammals appears to be much weaker than that in the previous studies on bats. In contrast to this finding, our recent study reported that duration tuning in the IC in guinea pigs appeared to be strong when it was measured using an appropriate temporal window. With such a temporal window, duration tuning was found to be compatible with that of echo-locating bats. In the present report, we further demonstrate that duration tuning in the IC of this species is established by interaction between excitation and GABAergic inhibition. In addition to overall increase in responsiveness, application of bicuculline(BIC), a GABA-A receptor antagonist, was found to significantly reduce or eliminate duration selectivity in 44 out of the 67 neurons that showed clear duration tuning from a sample of 340 neurons.
文摘The superior colliculus (SC) is a laminated midbrain structure responsible for visual orientation behaviors. In the mature SC, neurons in the stratum griseum superficiale (SGS) receive visual inputs that contribute to exciting premotor neurons in the stratum griseum intermediale (SGI) through a dorsoventral pathway. SGI activation generates feedback signals to the SGS through a ventrodorsal pathway. However, the developmental changes in signal transmission within the SC around the time of eye opening are not yet well understood. We compared the functional connections between the SGS and SGI before and after eye opening by imaging the neuronal population responses using a voltage-sensitive absorption dye in mouse SC slices. Electrophoresis of a fluorescent dye from the stimulating electrodes was used to fill the cells in the stimulated site. We here show that the dorsoventral transmission is present both before and after eye opening. This is in contrast to our previous finding that the ventrodorsal transmission develops after eye opening. Functions of intrinsic inhibitory systems mediated by gamma-aminobutyric acid were also investigated with the antagonist. The processes stained by electrophoresis from stimulating electrodes before eye opening were confined within the respective stimulated layers. Whereas, after eye opening, the processes were widely extended especially dorsoventrally and ventrodorsally invading the SGI and SGS, respectively. These corresponded well to the early component of voltage responses that is known to reflect the activation of presynaptic elements, presumably the axonal arborizations and varicosities. Thus, the optically-revealed functional connections between the SGS and SGI were correlated to the morphology.
基金supported by the National Basic Research Program of China (Grant Nos. 2011CB504506 and 2007CB512306)the National Natural Science Foundation of China (Grant Nos. 30970977 and 30730041)the Knowledge Innovation Project of the Chinese Academy of Sciences (Grant No. KSCX1-YW-R-36)
文摘Neuronal ion channels of different types often do not function independently but will inhibit or potentiate the activity of other types of channels,a process called cross-talk.The N-methyl-D-aspartate receptor (NMDA receptor) and the γ-aminobutyric acid type A receptor (GABAA receptor) are important excitatory and inhibitory receptors in the central nervous system,respectively.Currently,cross-talk between the NMDA receptor and the GABAA receptor,particularly in the central auditory system,is not well understood.In the present study,we investigated functional interactions between the NMDA receptor and the GABAA receptor using whole-cell patch-clamp techniques in cultured neurons from the inferior colliculus,which is an important nucleus in the central auditory system.We found that the currents induced by aspartate at 100 μmol L-1 were suppressed by the pre-perfusion of GABA at 100 μmol L-1,indicating cross-inhibition of NMDA receptors by activation of GABAA receptors.Moreover,we found that the currents induced by GABA at 100 μmol L-1 (IGABA) were not suppressed by the pre-perfusion of 100 μmol L-1 aspartate,but those induced by GABA at 3 μmol L-1 were suppressed,indicating concentration-dependent cross-inhibition of GABAA receptors by activation of NMDA receptors.In addition,inhibition of IGABA by aspartate was not affected by blockade of voltage-dependent Ca2+ channels with CdCl2 in a solution that contained Ca2+,however,CdCl2 effectively attenuated the inhibition of IGABA by aspartate when it was perfused in a solution that contained Ba2+ instead of Ca2+ or a solution that contained Ca2+ and 10 mmol L-1 BAPTA,a membrane-permeable Ca2+ chelator,suggesting that this inhibition is mediated by Ca2+ influx through NMDA receptors,rather than voltage-dependent Ca2+ channels.Finally,KN-62,a potent inhibitor of Ca2+/calmodulin-dependent protein kinase II (CaMKII),reduced the inhibition of IGABA by aspartate,indicating the involvement of CaMKII in this cross-inhibition.Our study demonstrates a functional interaction between NMDA and GABAA receptors in the inferior colliculus of rats.The presence of cross-talk between these receptors suggests that the mechanisms underlying information processing in the central auditory system may be more complex than previously believed.
基金This review was supported by the Key-Area Research and Development Program of Guangdong Province(2018B030331001)the National Natural Science Foundation of China(31630031 and 31930047)+3 种基金the Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence Fund(2019025),the Guangdong Provincial Key Laboratory of Brain Connectome and Behavior(2017B030301017)the Chinese Academy of Sciences International Partnership Program(172644KYSB20170004)the CAS President’s International Fellowship for Distinguished Scientists(2021DB0003)the Canadian Institutes of Health Research(#10677).
文摘The superior colliculus(SC),one of the most well-characterized midbrain sensorimotor structures where visual,auditory,and somatosensory information are integrated to initiate motor commands,is highly conserved across vertebrate evolution.Moreover,cell-type-specific SC neurons integrate afferent signals within local networks to generate defined output related to innate and cognitive behaviors.This review focuses on the recent progress in understanding of phenotypic diversity amongst SC neurons and their intrinsic circuits and long-projection targets.We further describe relevant neural circuits and specific cell types in relation to behavioral outputs and cognitive functions.The systematic delineation of SC organization,cell types,and neural connections is further put into context across species as these depend upon laminar architecture.Moreover,we focus on SC neural circuitry involving saccadic eye movement,and cognitive and innate behaviors.Overall,the review provides insight into SC functioning and represents a basis for further understanding of the pathology associated with SC dysfunction.
基金Project supported by the Shanghai Postdoctoral Scientific Program,the National Natural Science Foundation of China(No.31271158)the Doctoral Program of Higher Education from Ministry of Education of China+2 种基金the Innovation Program of Shanghai Municipal Education Commission(No.13ZZ002)the Shanghai Municipal Commission of Health and Family Planning,Science and Technology Commission of Shanghai Municipality(Nos.12ZR1441000 and 13PJ1401000)the Young 1000 Plan
文摘Eye-specific segregation in the dorsal lateral geniculate nucleus(dLGN) and superior colliculus(SC) starts from the embryonic stage and continues to develop postnatally until eye-opening in mice. However, there have been few systematic studies on the details of this developmental process. Here, we carried out time-dependent studies of eye-specific segregation in the dLGN and SC. Our results demonstrated that the development of eye-specific segregation in the SC is completed before postnatal day 12(P12), which is earlier than in the dLGN(P20). During the whole period, ipsilateral and overlapping axonal projections decreased continuously in both the dLGN and SC. On the other hand, contralateral axonal projections showed little change, except for a slight decrease between P8 and P20 in the dLGN.
基金Project supported by the National Natural Science Foundation of China.
文摘Neurons in superficial layers of the superior colliculus of the rabbit are classified into three types by their electrophysiological properties. Among them, two types belong to projecting neurons which send axons to the thalamic pulvinar (N=52) and dorsal lateral geniculate nucleus (N = 54) respectively. All other neurons are pooled into the third type (N=99). Projecting neurons of both types receive monosynaptic visual inputs via optic tract fibers of similar conduction velocity, indicating that in the superior colliculus of the rabbit, there is no difference in conduction velocity between the two pathways. They also receive trisynaptic inhibitory inputs, most likely via recurrent inhibitory circuits. The third type of neurons receives disynaptic optic and trisynaptic inhibitory inputs. The function of neurons of the third type is studied.
基金supported by the National Natural Science Foundation of China(31771195,81790640 and 82021002)a Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)+1 种基金ZJLab,Key Scientific Technological Innovation Research Project of the Ministry of Education,Sanming Project of Medicine in Shenzhen(SZSM202011015)Shanghai Health and Family Planning Commission(20164Y0096,20184Y0184)。
文摘Spontaneous activity in the brain maintains an internal structured pattern that reflects the external environment,which is essential for processing information and developing perception and cognition.An essential prerequisite of spontaneous activity for perception is the ability to reverberate external information,such as by potentiation.Yet its role in the processing of potentiation in mouse superior colliculus(SC)neurons is less studied.Here,we used electrophysiological recording,optogenetics,and drug infusion methods to investigate the mechanism of potentiation in SC neurons.We found that visual experience potentiated SC neurons several minutes later in different developmental stages,and the similarity between spontaneous and visually-evoked activity increased with age.Before eye-opening,activation of retinal ganglion cells that expressed ChR2 also induced the potentiation of spontaneous activity in the mouse SC.Potentiation was dependenton stimulus number and showed feature selectivity for direction and orientation.Optogenetic activation of parvalbumin neurons in the SC attenuated the potentiation induced by visual experience.Furthermore,potentiation in SC neurons was blocked by inhibiting the glutamate transporter GLT1.These results indicated that the potentiation induced by a visual stimulus might play a key role in shaping the internal representation of the environment,and serves as a carrier for short-term memory consolidation.
基金This work was supported by the grants(Nos.30970972 and 108096)from the National Natural Science Foundation of China(Grant Nos.30970972 and 108096)the State Education Ministry of China.
文摘The neural modulation in central auditory system plays an important role in perception and processing of sound signal and auditory cognition.The inferior colliculus(IC)is both a relay station in central auditory pathway and a sub-cortical auditory center doing the sound signal processing.IC is also modulated by the descending projections from the cortex and auditory thalamus,medial geniculate body,and these neural modulations not only can affect ongoing sound signal processing but can also induce plastic changes in IC.
基金supported by the National Natural Science Foundation of China(Grant No.31470987)the National Basic Research Development Program of China(Grant No.2015CB351800)“985”grants from Peking University for Physiological Psychology and China Postdoctoral Science Foundation(Grant No.2016M601066)
文摘In studies of auditory perception, a dichotomy between envelope and temporal fine structure(TFS) has been emphasized. It has been shown that frequency-following responses(FFRs) in the rat inferior colliculus can be divided into the envelope component(FFREnv)and the temporal fine structure component(FFRTFS). However, the existing FFR models cannot successfully separate FFREnv and FFRTFS. This study was to develop a new FFR model to effectively distinguish FFREnv from FFRTFS by both combining the advantages of the two existing FFR models and simultaneously adding cellular properties of inferior colliculus neurons. To evaluate the validity of the present model, correlations between simulated FFRs and experimental data from the rat inferior colliculus were calculated. Different model parameters were tested, FFRs were calculated, and the parameters with highest prediction were chosen to establish an ideal FFR model. The results indicate that the new FFR model can provide reliable predictions for experimentally obtained FFREnv and FFRTFS.
文摘Data from studies analyzing the differentiation and functional connectivity of embryo nic neural tissue grafted into the mammalian nervous system has led to the clinical testing of the fetal graft approach in patients with neurodegenerative disease.While some success has been achieved,ethical concerns have led to a search for alternative therapeutic strategies,mostly exploring the use of neural precursors or neurons derived from pluripotent stem cells to replace damaged host neurons and restore lost circuitries.These more recent studies address questions of graft viability,differentiation,and connectivity similar to those posed by researchers in earlier fetal transplant work,thus reviews of the fetal graft literature may inform and help guide ongoing research in the stem cell/organoid field.This brief review describes some key observations from research into the transplantation of neural tissue into the rat visual syste m,focusing on grafts of the fetal supe rior colliculus(tectal grafts) into neonatal or adult hosts.In neonate hosts,grafts quickly develop connections with the underlying host mid b rain and attain a morphology typical of mature grafts by about 2 weeks.G rafts consistently contain numerous localized regions which,based on neurofibrillar staining,neuronal morphology(Golgi),neurochemistry,receptor expression,and glial architecture,are homologous to the stratum griseum supe rficiale of normal superior colliculus.These localized "patches" are also seen after explant culture and when donor tectal tissue is dissociated and reaggregated prior to transplantation.In almost all circumstances,host retinal innervation is restricted to these localized patches,but only those that are located adjacent to the graft surfa ce.Synapses are formed and there is evidence of functional drive.The only exception occurs when Schwann cells are added to dissociated tecta prior to reaggregation.In these co-grafts,the peripheral glia appear to compete with local target fa ctors and host retinal ingrowth is more widespread.Other afferent systems(e.g.,host co rtex,serotonin) show different patterns of innervation.The host cortical input originates more from extrastriate regions and establishes functional excitato ry synapses with grafted neurons.Finally,when grafted into optic tra ct lesions in adult rat hosts,spontaneously regrowing host retinal axons retain the capacity to selectively innervate the localized patches in embryonic tectal grafts,showing that the specific affinities between adult retinal axons and their targets are not lost during regeneration.While the research described here provides some pertinent information about development and plasticity in visual pathways,a more general aim is to highlight how the review of the extensive fetal graft lite rature may aid in an appreciation of the positive(and negative) fa ctors that influence survival,differentiation,connectivity and functionality of engineered cells and organoids transplanted into the central nervous system.
基金supported by the National Natural Science Foundation of China, Nos.31830035, 91732304, 91632303, 81661148053, and 31771156(all to FQX)the Key-Area Research and Development Program of Guangdong Province of China, No.2018B030331001(to FQX)+4 种基金the SIAT Innovation Program for Excellent Young Researchers of China,No.E1G023(to FJ)the Guangdong Basic and Applied Basic Research Foundation of China, No.2021A1515011235(to FQX)Shenzhen Key Laboratory of Viral Vectors for Biomedicine of China, No.ZDSYS20200811142401005(to FQX)the National Basic Research Program(973 Program)of China, No.2015CB755600(to FQX)the Strategic Priority Research Program(B)of China, No.XDB32030200(to FQX)
文摘Mapping neural circuits is critical for understanding the structure and function of the nervous system.Engineered viruses are a valuable tool for tracing neural circuits.However,current tracers do not fully meet the needs for this approach because of various drawbacks,such as toxicity and characteristics that are difficult to modify.Therefore,there is an urgent need to develop a new tracer with low toxicity and that allows for long-term studies.In this study,we constructed an engineered Sindbis virus(SINV)expressing enhanced green fluorescent protein(EGFP)reporter gene(SINV-EGFP)and found that it had no significant difference in biological characterization compared with the wild-type Sindbis virus in BHK-21 cells and neurons in vitro.We injected the virus into the visual circuit of mouse brain and found that the virus infected neurons in the local injected site and anterogradely spread in the neural circuits.Although the efficiency of transmission was limited,the findings demonstrate that SINV can be used as a new anterograde tracer to map neural circuits in mouse brain and that it spreads exclusively in the anterograde direction.Further,use of SINV in mouse brain research will provide longer time windows for circuit tracing than is possible with herpes simplex virus and vesicular stomatitis virus tracers.
文摘Adult guinea pigs with normal Preyer’s reflexes were used in this experiment and were di-vided into 3 groups according to the intensity of noise and exposure time.Auditory brainstemevoked response was recorded before and after exposure to noise.Clicks were presented monaurallyat a rate of high (50Hz) as well as low (10Hz).The superior olive and inferior colliculus were ob-served under an electron microscope after the guinea pigs were exposured to 110dB noise for30min.The average shift of wave Ⅳ amplitude-intensity function curve was more than that ofwave Ⅰ after exposure to intensive noise.The difference value of wave \ latency from low(10Hz) to high (50Hz) stimulus click rate decreased and was negatively correlated with the exposuretime.Ⅰ-Ⅴ,Ⅲ-Ⅴ and Ⅳ-Ⅴ interpeak latencies were shorter after exposure to noise.Themitochondria and neurilemma swelling were found in the superior olive and inferior colliculus afterexposure,Some mechanisms of the changes of auditory center were discussed in this paper.
基金supported by grants from the National Key R&D Program of China(2017YFE0103400)the National Nature Science Foundation of China(81470628).
文摘Parvalbumin-positive retinal ganglion cells(PV+RGCs)are an essential subset of RGCs found in various species.However,their role in transmitting visual information remains unclear.Here,we characterized PV+RGCs in the retina and explored the functions of the PV+RGC-mediated visual pathway.By applying multiple viral tracing strategies,we investigated the downstream of PV+RGCs across the whole brain.Interestingly,we found that the PV+RGCs provided direct monosynaptic input to PV+excitatory neurons in the superficial layers of the superior colliculus(SC).Ablation or suppression of SC-projecting PV+RGCs abolished or severely impaired the flight response to looming visual stimuli in mice without affecting visual acuity.Furthermore,using transcriptome expression profiling of individual cells and immunofluorescence colocalization for RGCs,we found that PV+RGCs are predominant glutamatergic neurons.Thus,our findings indicate the critical role of PV+RGCs in an innate defensive response and suggest a non-canonical subcortical visual pathway from excitatory PV+RGCs to PV+SC neurons that regulates looming visual stimuli.These results provide a potential target for intervening and treating diseases related to this circuit,such as schizophrenia and autism.
基金This work was supported by the National Natural Science Foundation of China (Grant No. 39870246) and the research fund from the National Science Foundation of USA (Grant No. NSF IBN 9604238).
文摘In order to explore the possible mechanism of corticofugal modulation of excitatory frequency tuning curves (EFTCs) of midbrain neurons, we examined the change of sharpness, frequency-intensity response area, minimum threshold of both EFTCs and inhibitory frequency tuning curves (IFTCs) of inferior collicular neurons during corticofugal modulation using two-tone inhibition paradigm and micro-electrical stimulation technique. Our data showed that corticofugal inhibition increased sharpness, minimum threshold, and decreased the frequency-intensity response area of EFTCs, at the same time it decreased the sharpness, minimum threshold but increased the frequency-intensity response area of IFTCs. The opposite results were observed for EFTCs and IFTCs of corticofugally facilitated inferior collicular neurons. During corticofugal inhibition, the percent change of frequency-intensity response area of EFTCs had significant correlation with the percent change of that of IFTCs. These data suggest that cortical
