A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes.
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ABSTRACT:
SUBMITTER: Guo W
PROVIDER: S-EPMC8568936 | biostudies-literature | 2021 Nov
REPOSITORIES: biostudies-literature
Publications
A Brainstem reticulotegmental neural ensemble drives acoustic startle reflexes.
Guo Weiwei W Fan Sijia S Xiao Dan D Dong Hui H Xu Guangwei G Wan Zhikun Z Ma Yuqian Y Wang Zhen Z Xue Tian T Zhou Yifeng Y Li Yulong Y Xiong Wei W
Nature communications 20211104 1
The reticulotegmental nucleus (RtTg) has long been recognized as a crucial component of brainstem reticular formation (RF). However, the function of RtTg and its related circuits remain elusive. Here, we report a role of the RtTg in startle reflex, a highly conserved innate defensive behaviour. Optogenetic activation of RtTg neurons evokes robust startle responses in mice. The glutamatergic neurons in the RtTg are significantly activated during acoustic startle reflexes (ASR). Chemogenetic inhib ...[more]
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Project description:In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.
| S-EPMC11527297 | biostudies-literature
Project description:In the developing brain, groups of neurons organize into functional circuits that direct diverse behaviors. One such behavior is the evolutionarily conserved acoustic startle response, which in zebrafish is mediated by a well-defined hindbrain circuit. While numerous molecular pathways that guide neurons to their synaptic partners have been identified, it is unclear if and to what extent distinct neuron populations in the startle circuit utilize shared molecular pathways to ensure coordinated development. Here, we show that the planar cell polarity (PCP)-associated atypical cadherins Celsr3 and Celsr2, as well as the Celsr binding partner Frizzled 3a/Fzd3a, are critical for axon guidance of two neuron types that form synapses with each other: the command-like neuron Mauthner cells that drive the acoustic startle escape response, and spiral fiber neurons which provide excitatory input to Mauthner cells. We find that Mauthner axon growth towards synaptic targets is vital for Mauthner survival. We also demonstrate that symmetric spiral fiber input to Mauthner cells is critical for escape direction, which is necessary to respond to directional threats. Moreover, we identify distinct roles for Celsr3 and Celsr2, as Celsr3 is required for startle circuit development while Celsr2 is dispensable, though Celsr2 can partially compensate for loss of Celsr3 in Mauthner cells. This contrasts with facial branchiomotor neuron migration in the hindbrain, which requires Celsr2 while we find that Celsr3 is dispensable. Combined, our data uncover critical and distinct roles for individual PCP components during assembly of the acoustic startle hindbrain circuit.
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Project description:Functional role of the acoustic reflex in preventing over stimulation of the inner auditory system by decreasing sound intensity along with the previous reports of acoustic reflex abnormalities in individuals having hyperacusis point towards the involvement of acoustic reflex deficit in the origin of hyperacusis especially when any medical condition leading to hyperacusis is not associated. However this issue remains contradictory owing to limited comprehensive investigation. This study was undertaken to ascertain the relationship between hyperacusis and the acoustic reflex. Threshold, amplitude and latency of the acoustic reflex were measured in two different groups of individuals having hyperacusis; Group 1: 14 individuals having hyperacusis with hearing loss (HwHL) and Group 2: 17 individuals having hyperacusis without hearing loss (HwoHL). Control group (Group 3) consisted of 15 normal hearing individuals who never experienced hyperacusis. Result showed a significant group effect on all the measured characteristics of the acoustic reflex. ARTs were found to be significantly higher in HwHL and HwoHL when compared to NHwoH. ARTs were statistically similar for HwoHL and NHwoH. HwoHL's ARAs and ARLs were significantly smaller and prolonged, respectively, when compared to HwHL and NHwoH. HwHL and NHwoH had statistically similar ARAs and ARLs. This study confirms acoustic reflex abnormalities in some individuals having hyperacusis with or without hearing loss. It further highlight the importance of involving acoustic reflex testing in the assessment of hyperacusis especially when hyperacusis is not associated with hearing loss or any other medical condition that may lead to hyperacusis.
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Project description:Prepulse inhibition (PPI) is an acoustic startle paradigm that has been used as an operational measure of sensorimotor gating. Many patients with schizophrenia have impaired PPI, and several lines of evidence suggest that PPI may represent a heritable endophenotype in this disease. We examined startle magnitude and latencies in 40 schizophrenia patients, 58 first-degree relatives of these patients, and 100 healthy controls. After removing low-startlers, we investigated PPI and startle habituation in 34 schizophrenia patients, 43 relatives, and 86 control subjects. Heritability analyses were conducted using a variance-component approach. We found significant heritability of 45% for PPI at the 60-ms interval and 67% for startle magnitude. Onset latency heritability estimates ranged between 39% and 90% across trial types, and those for peak latency ranged from 29% to 68%. Heritability of startle habituation trended toward significance at 31%. We did not detect differences between controls and either schizophrenia patients or their family members for PPI, startle magnitude, or habituation. Startle latencies were generally longer in schizophrenia patients than controls. The heritability findings give impetus to applying genetic analyses to PPI variables, and suggest that startle latency may also be a useful measure in the study of potential endophenotypes for schizophrenia.
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| S-EPMC5534953 | biostudies-literature