A review of the neural basis underlying the acoustic startle response with a focus on recent developments in mammals

Zheng, Alice; Schmid, Susanne

doi:10.1016/j.neubiorev.2023.105129

Cited by 21 publications

(10 citation statements)

References 94 publications

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“…Central to the circuit are the Mauthner cells, a pair of large reticulospinal neurons located in the hindbrains of some amphibians 9 and fish 6 , including zebrafish. These neurons are functionally similar to startle-associated giant reticulospinal neurons in the mammalian caudal pontine reticular nucleus 10,11 . In five day old larval zebrafish (5 days postfertilization, dpf), intense acoustic stimuli perceived by hair cells in the ear and lateral line robustly elicit Mauthner-mediated fast escape responses.…”

Section: Introductionmentioning

confidence: 84%

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Meserve,

Navarro,

Ortiz

et al. 2024

Preprint

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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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Section: Introductionmentioning

confidence: 84%

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Meserve,

Navarro,

Ortiz

et al. 2024

Preprint

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“…Another intention of the current study was to investigate how persistent BLA inhibition affected anxiety like behavior in late adolescence (P54-55), and if the observed changes to corticolimbic innervation drove any alterations to anxiety, as measured by arousal and threat perception. The ASR is highly evolutionarily conserved and has been shown in both humans and rodents to be a reliable metric of anxiety (Zheng & Schmid, 2023; Granata et al, 2022; Davis et al, 1982). This reflex relies on quick relay of information via the primary acoustic startle pathway, including the auditory nerve, the ventral cochlear nucleus, the dorsal nucleus of the lateral lemniscus, the caudal pontine reticular nucleus, spinal interneurons, and spinal motor neurons (Davis et al, 1993).…”

Section: Discussionmentioning

confidence: 99%

Effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and anxiety behaviors

Cody,

Artur de la Villarmois,

Miguelez Fernandez

et al. 2024

Preprint

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Early postnatal life is a dynamic period of brain development that involves a coordinated symphony of circuit maturation. As many regions within the brain continue to develop and mature postnatally, external stimuli impact this development and regulate the degree of connectivity to other brain areas. Since subcortical limbic regions undergo substantial synapse formation and pruning during early development while higher-order areas such as the prefrontal cortex (PFC) mature during adolescence, early postnatal life and adolescence are two sensitive periods when limbic and prefrontal regions form functional connections in response to external stimuli and neuronal activity. Thus, activity within limbic regions over the course of development can affect the strength and quantity of efferent connections to cortical areas. Prior work has shown hyper-innervation of glutamatergic basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) in the adolescent time period following rearing in an adverse early life environment, but how these ELA-induced connectivity changes alter the startle circuitry required to execute a startle response and whether the BLA-PFC pathway is responsible for previously reported blunted startle response remains unknown. We directly tested whether BLA activity during a discrete adolescent period altered later anxiety behaviors, and if behavioral changes were driven by altered PFC innervation. To test these questions, we exposed rat pups to an ELA model of maternal separation on postnatal days (P) 2-21. Rats then underwent an injection of an inhibitory DREADD in the BLA in order to silence the excitatory projections during the adolescent time period of P33-39. Finally, rats were tested in an acoustic startle paradigm in late adolescence to assess the effects of reduced BLA-PFC connectivity on the ELA-induced blunted startle response. Density, intensity, and volume of axonal boutons in the BLA projecting PFC neurons were then assessed to elucidate how BLA inhibition during adolescence affects innervation later in life. These results explore how altered early life environments may affect the development of anxiety-related circuitry and anxiety responses later in life, and how rescue of this maladaptive response may be sex and developmentally specific.

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“…Our advanced analyses demonstrate that the baseline startle response curve is scaled in both the leftward and upward directions in Cntnap2 KO rats, which confirms and expands on previous studies reporting higher startle responses in these rats [ 28 , 30 ]. As the baseline startle response is determined by PnC giant neuronal activity [ 7 , 24 , 26 ], the hyperreactivity to sound could be a result of hyperexcitability of PnC giant neurons or of altered excitatory glutamatergic input [ 18 ]. Scott et al [ 29 ] found no differences in auditory brainstem responses between adult Cntnap2 WT and KO rats, indicating that there are no changes in sound processing at the level of the auditory nerve, or cochlear nucleus.…”

Section: Discussionmentioning

confidence: 99%

“…The neural pathways involved in startle and PPI have been investigated through diverse studies utilizing lesioning [ 6 , 7 ], decortication [ 8 ], behavioral investigations [ 9 – 12 ], optogenetics [ 13 – 16 ], chemogenetics [ 17 ], pharmacological investigations [ 18 – 22 ], as well as electrical stimulation [ 23 ]. While the startle pathway has been well defined as a highly conserved short pathway in the brainstem (for review see [ 4 , 24 ]), PPI is thought to be mediated through a feed-forward mechanism originating in the brainstem and involving midbrain and higher-order brain structures (Supplemental Fig. 1 ; for review see [ 5 ]).…”

Section: Introductionmentioning

confidence: 99%

Assessing the Cntnap2 knockout rat prepulse inhibition deficit through prepulse scaling of the baseline startle response curve

El-Cheikh Mohamad,

Möhrle,

Haddad

et al. 2023

Transl Psychiatry

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Many neurodevelopmental disorders, including autism spectrum disorder (ASD), are associated with changes in sensory processing and sensorimotor gating. The acoustic startle response and prepulse inhibition (PPI) of startle are widely used translational measures for assessing sensory processing and sensorimotor gating, respectively. The Cntnap2 knockout (KO) rat has proven to be a valid model for ASD, displaying core symptoms, including sensory processing perturbations. Here, we used a novel method to assess startle and PPI in Cntnap2 KO rats that allows for the identification of separate scaling components: startle scaling, which is a change in startle amplitude to a given sound, and sound scaling, which reflects a change in sound processing. Cntnap2 KO rats show increased startle due to both an increased overall response (startle scaling) and a left shift of the sound/response curve (sound scaling). In the presence of a prepulse, wildtype rats show a reduction of startle due to both startle scaling and sound scaling, whereas Cntnap2 KO rats show normal startle scaling, but disrupted sound scaling, resulting in the reported PPI deficit. These results validate that startle and sound scaling by a prepulse are indeed two independent processes, with only the latter being impaired in Cntnap2 KO rats. As startle scaling is likely related to motor output and sound scaling to sound processing, this novel approach reveals additional information on the possible cause of PPI disruptions in preclinical models.

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A review of the neural basis underlying the acoustic startle response with a focus on recent developments in mammals

Cited by 21 publications

References 94 publications

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Celsr3 drives development and connectivity of the acoustic startle hindbrain circuit

Effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and anxiety behaviors

Assessing the Cntnap2 knockout rat prepulse inhibition deficit through prepulse scaling of the baseline startle response curve

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