Research Progress in the Study of Startle Reflex to Disease States

Zhang, Junfeng; Wang, Meng; Wei, Baoyu; Shi, Jiangwei; Yu, Tao

doi:10.2147/ndt.s351667

Cited by 11 publications

(8 citation statements)

References 56 publications

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“…These findings mirror those of previously documented mouse models of mania [ 42 , 44 ] and patients with BD [ 48 – 50 ]. Some overlapping phenotypes have been observed in patients with ASD and SCZ or animal models with Pcdh15 deletion [ 43 , 45 – 47 ].…”

Section: Discussionmentioning

confidence: 99%

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Mori,

Inami,

Ikeda

et al. 2024

Transl Psychiatry

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Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.

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Section: Discussionmentioning

confidence: 99%

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Mori,

Inami,

Ikeda

et al. 2024

Transl Psychiatry

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“…The startle response is a sudden motor response for protecting the individual from potentially harmful stimuli [6,9]. Changes of the startle reflex can be related to cochlear damage by aging, noise exposure or ototoxic drugs [10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

“…Acoustic, vestibular or tactile startle can be distinguished in mice [6]. Enhancement or inhibition of the acoustic startle reflex and its modulation was described in various diseases or conditions affecting the cochlea or the central nervous system [7][8][9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

KCNQ4 potassium channel subunit deletion leads to exaggerated acoustic startle reflex in mice

et al. 2023

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The potassium voltage-gated channel subfamily Q member 4 (KCNQ4) subunit forms channels responsible for M-current, a muscarine-sensitive potassium current regulating neuronal excitability. In contrast to other KCNQ subunits, its expression is restricted to the cochlear outer hair cells, the auditory brainstem and other brainstem nuclei in a great overlap with structures involved in startle reflex. We aimed to show whether startle reflexis affected by the loss of KCNQ4 subunit and whether these alterations are similar to the ones caused by brainstem hyperexcitability. Young adult KCNQ4 knockout mice and wild-type littermates, as well as mice expressing hM3D chemogenetic actuator in the pontine caudal nucleus and neurons innervating it were used for testing acoustic startle. The acoustic startle reflex was significantly increased in knockout mice compared with wild-type littermates. When mice expressing human M3 muscarinic (hM3D) in nuclei related to startle reflex were tested, a similar increase of the first acoustic startle amplitude and a strong habituation of the further responses was demonstrated. We found that the acoustic startle reflex is exaggerated and minimal habituation occurs in KCNQ4 knockout animals. These changes are distinct from the effects of the hyperexcitability of nuclei involved in startle. One can conclude that the exaggerated startle reflex found with the KCNQ4 subunit deletion is the consequence of both the cochlear damage and the changes in neuronal excitability of startle networks.

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“…Previous studies investigated the facilitating effects of acoustic startle stimuli on cortical and subcortical areas ( Mueller-Pfeiffer et al, 2014 ; Zhang et al, 2022 ). However, few studies investigated the activation of the non-motor cortex and potential brain networks.…”

Section: Discussionmentioning

confidence: 99%

“…Although the exact neural mechanism by which loud sounds induce the SE is unclear, it most likely involves some known subcortical and cortical pathways in the brain ( Marinovic and Tresilian, 2016 ; Carlsen and Maslovat, 2019 ). In mammalian studies, two neural pathways (the cortico-striato-pallido-pontine network and an independent circuit from the central nucleus of the amygdala to the pontine reticular nucleus) have been found to participate in the modulation of prepulse inhibition of the auditory startle reflex ( Cano et al, 2021 ; Zhang et al, 2022 ). Moreover, activity in the supplementary motor area (SMA), supramarginal gyrus, cingulate cortex, anterior insula and cerebellar lobule was also associated with startle stimuli ( Mueller-Pfeiffer et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

Altered frontoparietal activity in acoustic startle priming tasks during reticulospinal tract facilitation: An fNIRS study

Xia

He²,

Wei³

et al. 2023

Front. Neurosci.

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BackgroundBecause it is one of the important pathways for promoting motor recovery after cortical injury, the function of the reticulospinal tract (RST) has received increasing attention in recent years. However, the central regulatory mechanism of RST facilitation and reduction of apparent response time is not well understood.ObjectivesTo explore the potential role of RST facilitation in the acoustic startle priming (ASP) paradigm and observe the cortical changes induced by ASP reaching tasks.MethodsTwenty healthy participants were included in this study. The reaching tasks were performed with their left and right hands. Participants were instructed to get ready after the warning cue and complete the reach as soon as they heard the Go cue. Half of the testing trials were set as control trials with an 80-dB Go cue. The other half of the trials had the Go cue replaced with 114-dB white noise to evoke the StartleReact effect, inducing reticulospinal tract facilitation. The response of the bilateral sternocleidomastoid muscle (SCM) and the anterior deltoid was recorded via surface electromyography. Startle trials were labeled as exhibiting a positive or negative StartleReact effect, according to whether the SCM was activated early (30–130 ms after the Go cue) or late, respectively. Functional near-infrared spectroscopy was used to synchronously record the oxyhemoglobin and deoxyhemoglobin fluctuations in bilateral motor-related cortical regions. The β values representing cortical responses were estimated via the statistical parametric mapping technique and included in the final analyses.ResultsSeparate analyses of data from movements of the left or right side revealed significant activation of the right dorsolateral prefrontal cortex during RST facilitation. Moreover, left frontopolar cortex activation was greater in positive startle trials than in control or negative startle trials during left-side movements. Furthermore, decreased activity of the ipsilateral primary motor cortex in positive startle trials during ASP reaching tasks was observed.ConclusionThe right dorsolateral prefrontal cortex and the frontoparietal network to which it belongs may be the regulatory center for the StartleReact effect and RST facilitation. In addition, the ascending reticular activating system may be involved. The decreased activity of the ipsilateral primary motor cortex suggests enhanced inhibition of the non-moving side during the ASP reaching task. These findings provide further insight into the SE and into RST facilitation.

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Research Progress in the Study of Startle Reflex to Disease States

Cited by 11 publications

References 56 publications

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

Mice with deficiency in Pcdh15, a gene associated with bipolar disorders, exhibit significantly elevated diurnal amplitudes of locomotion and body temperature

KCNQ4 potassium channel subunit deletion leads to exaggerated acoustic startle reflex in mice

Altered frontoparietal activity in acoustic startle priming tasks during reticulospinal tract facilitation: An fNIRS study

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