Life-Course Contribution of Prenatal Stress in Regulating the Neural Modulation Network Underlying the Prepulse Inhibition of the Acoustic Startle Reflex in Male Alzheimer’s Disease Mice

Abstract The prepulse inhibition (PPI) of the acoustic startle reflex (ASR), as an index of sensorimotor gating, is one of the most extensively used paradigms in the field of neuropsychiatric disorders. Few studies have examined how prenatal stress (PS) regulates the sensorimotor gating during the lifespan and how PS modifies the development of amyloid-beta (Aβ) pathology in brain areas underlying the PPI formation. We followed alternations in corticosterone levels, learning and memory, and the PPI of the ASR measures in APPNL-G-F/NL-G-F offspring of dams exposed to gestational noise stress. In-depth quantifications of the Aβ plaque accumulation were also performed at 6 months. The results indicated an age-dependent deterioration of sensorimotor gating, long-lasting PS-induced abnormalities in PPI magnitudes, as well as deficits in spatial memory. The PS also resulted in a higher Aβ aggregation predominantly in brain areas associated with the PPI modulation network. The findings suggest the contribution of a PS-induced hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in regulating the PPI modulation substrates leading to the abnormal development of the neural protection system in response to disruptive stimuli. The long-lasting HPA axis dysregulation appears to be the major underlying mechanism in precipitating the Aβ deposition, especially in brain areas contributed to the PPI modulation network.

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Personality Correlates of Prepulse Inhibition of the Startle Reflex at Three Lead Intervals

Journal of Psychophysiology ◽

10.1027//0269-8803.16.2.82 ◽

2002 ◽

Vol 16 (2) ◽

pp. 82-91 ◽

Cited By ~ 9

Author(s):

Philip J. Corr ◽

Allison Tynan ◽

Veena Kumari

Keyword(s):

Prepulse Inhibition ◽

Acoustic Startle ◽

Sensorimotor Gating ◽

Startle Reflex ◽

Incentive Motivation ◽

Acoustic Startle Reflex ◽

Pulse Interval ◽

Causal Explanations ◽

Psychosis Proneness ◽

Psychometric Measures

Abstract The acoustic startle reflex (ASR) is modulated by a number of experimental factors, the most important of which in the field of psychopathology is weak prestimulation: The ASR is reliably reduced if preceded briefly by a weaker stimulus (i. e., the prepulse), an effect known as prepulse inhibition (PPI). PPI is thought to reflect centrally-mediated sensorimotor gating of stimuli, preventing cognitive overload and behavioural confusion. PPI is impaired in a variety of psychiatric disorders, notably schizophrenia, as well as in individuals who score high on psychometric measures of psychosis proneness. Two experiments examined the association of personality (trait emotionality) and PPI at three prepulse-to-pulse intervals (30, 60 and 120 ms). Consistent with previous reports, findings from both experiments showed highly significant PPI (defined as percentage reduction in the amplitude of the ASR), which increased with prepulse-to-pulse interval (30 < 60 < 120 ms). A novel finding was that, in both experiments 1 (N = 36) and 2 (N = 63), the trait of neuroticism was negatively correlated with PPI; in addition, a measure of positive incentive motivation (i. e., Behavioural Activation System, Drive subscale; BAS-Drive) was also negatively correlated with PPI. These trait emotionality associations were independent of gender. Possible causal explanations of these personality associations are outlined. It is concluded that, in order to clarify the aetiological role of sensorimotor gating in psychopathological conditions (e. g., schizophrenia, often entailing emotional activation), trait emotionality variance should be routinely examined in future PPI studies.

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Improved assessment of sensorimotor gating in animal models relevant to ASD: A data modelling approach to quantify PrePulse Inhibition of the acoustic startle reflex

Journal of Neuroscience Methods ◽

10.1016/j.jneumeth.2016.11.007 ◽

2017 ◽

Vol 276 ◽

pp. 13-22 ◽

Cited By ~ 1

Author(s):

Stéphanie Degroote ◽

Darel Hunting ◽

Larissa Takser

Keyword(s):

Animal Models ◽

Prepulse Inhibition ◽

Acoustic Startle ◽

Sensorimotor Gating ◽

Startle Reflex ◽

Acoustic Startle Reflex ◽

Data Modelling ◽

Modelling Approach

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Prepulse Inhibition of the Auditory Startle Reflex Assessment as a Hallmark of Brainstem Sensorimotor Gating Mechanisms

10.20944/preprints202008.0356.v1 ◽

2020 ◽

Author(s):

Ricardo Gómez-Nieto ◽

Sebastian Hormigo ◽

Dolores E. López

Keyword(s):

Prepulse Inhibition ◽

Sensory Modality ◽

Acoustic Startle ◽

Sensorimotor Gating ◽

Startle Reflex ◽

Acoustic Startle Reflex ◽

Normal Brain ◽

Specific Stimulus ◽

Gating Mechanisms ◽

Potential Marker

When a low-salience stimulus of any type of sensory modality—auditory, visual, tactile—shortly precedes an unexpected startle-like stimulus, such as the acoustic startle reflex, the startle motor reaction becomes less pronounced or is even abolished. This phenomenon is known as prepulse inhibition (PPI), and it provides operational measures of information processing by filtering out irrelevant stimuli. Because PPI implies plasticity of a reflex and is related to automatic or attentional processes, depending on the interstimulus intervals, this behavioral paradigm might be considered a potential marker of short- and long-term plasticity. Assessment of PPI is directly related to the examination of neural sensorimotor gating mechanisms, which are plastic adaptive operations for preventing overstimulation and help the brain focus on a specific stimulus among other distracters. Despite their obvious importance in normal brain activity, little is known about the intimate physiology, circuitry, and neurochemistry of sensorimotor gating mechanisms. In this work, we extensively review the current literature focusing on studies that used state-of-the-art techniques to interrogate the neuroanatomy, connectomics, neurotransmitter-receptor functions, and sex-derived differences in the PPI process, and how we can harness it as biological marker in neurological and psychiatric pathology.

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