Name: using a murine model of psychosocial stress in pregnancy as a translationally relevant paradigm for psychiatric disorders in mothers and infants
Uploaded: 2021-06-13T13:00:00
Description: Watch this Scientific Journal Video about Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants at JoVE.com

The authors wish to acknowledge support from the National Institute of General Medical Sciences T32 GM063483-14 grant and Cincinnati Children&#39;s Research Foundation. For data adapted from Zoubovsky et al., 2019, Creative Common License can be found at the following location: http://creativecommons.org/licenses/by/4.0/.

All animal experiments described were approved by the Animal Care and Use Committee at Cincinnati Children&#39;s Medical Center and were in accordance with the National Institutes of Health guidelines. Ad libitum access to standard rodent chow and water was provided at all times to mice, including during the CGS paradigm. Mice were housed on a 14 h/10 h light-dark cycle (lights on 06:00 h) unless otherwise specified (i.e., exposure to lights overnight).
1. Preparing for timed matings</p...

<ol>
	<li>Hillerer, K. M., Reber, S. O., Neumann, I. D., Slaterry, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Exposure+to+chronic+pregnancy+stress+reverses+peripartum-associated+adaptations:+implications+for+postpartum+anxiety+and+mood+disorders.">Exposure to chronic pregnancy stress reverses peripartum-associated adaptations: implications for postpartum anxiety and mood disorders.</a> Endocrinology. 152 (10), 3930-3940 (2011).</li><li>Hillerer, K. M., Neumann, I. D., Slaterry, D. 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N., Elmore, S., Barnard, K. E., Carr, D. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dysregulation+of+the+hypothalamic-pituitary-adrenal+axis+in+postpartum+depression.">Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression.</a> Biological Research for Nursing. 8 (3), 210-222 (2007).</li><li>Nierop, A., Bratsikas, A., Zimmermann, R., Ehlert, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Are+stress-induced+cortisol+changes+during+pregnancy+associated+with+postpartum+depressive+symptoms.">Are stress-induced cortisol changes during pregnancy associated with postpartum depressive symptoms.</a> Psychosomatic Medicine. 68 (6), 931-937 (2006).</li><li>Ulrich-Lai, Y. M., Herman, J. 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C., P&#233;rez-Diaz, F., Hanoun, N., Cohen-Salmon, C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prepartum+chronic+ultramild+stress+increases+corticosterone+and+estradiol+levels+in+gestating+mice:+Implications+for+postpartum+depressive+disorders.">Prepartum chronic ultramild stress increases corticosterone and estradiol levels in gestating mice: Implications for postpartum depressive disorders.</a> Psychiatry Research. 137 (12), 123-130 (2005).</li><li>Zoubovsky, S. 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Exposing the pregnant mice to CGS perturbs postpartum maternal neuroendocrine function, including HPA axis response to novel stressors, and is associated with various behavioral abnormalities relevant to perinatal mood and anxiety disorders. Given that the model employs utilization of an environmental risk factor, higher phenotypic variation is expected than otherwise observed in genetic models22. Nevertheless, results obtained from application of the CGS paradigm can be consistent across research...

The mechanisms underlying increased susceptibility to neuropsychiatric disorders in mothers and infants following adverse maternal exposures in the peripartum period remain largely unknown. Substantial maternal physiological alterations occur during pregnancy and the transition to the postpartum period, including several neuroendocrine adaptations that are hypothesized to be critical not only for healthy offspring neurodevelopment but also for preserving maternal mental health1,2. At the level of the maternal hypothalamic pituitary adrenal (HPA) axis, adaptions in both circadian and stress-induced levels of glucocorticoid release are observed, including a more flattened rhythm of diurnal HPA axis activity and dampened HPA axis response to acute stressors3,4,5. Given that enhanced HPA axis activity is reported in a subset of women with postpartum affective dysregulation, including increased levels of circulating glucocorticoids and inhibited negative feedback6,7,8, exposure to stressors that result in increased postpartum stress reactivity and prevent maternal HPA axis adaptions are thought to increase susceptibility to neuropsychiatric disorders.
To elucidate the effects of stress on affective dysregulation in mothers and infants, several rodent models of stress in the peripartum period have been generated. A majority of these models are characterized by the application of physical stressors that result in homeostatic challenges and alterations in dam physiological status9, such as chronic restraint stress10 and swim stress during gestation11, or postpartum shock exposure12. Although these paradigms have been shown to result in the emergence of postpartum depressive-like behaviors and alterations in maternal care10,11,12, they have been limited by their inability to accurately capture the psychosocial nature of stressors commonly experienced by human mothers. This becomes particularly important when attempting to reveal the neuroendocrine consequences of chronic stress in the peripartum period, given that processing of different types of stressors is thought to be mediated by varying neural networks orchestrating HPA axis activation9.
In order to overcome this limitation, several groups have designed stress paradigms employing psychosocial insults or a combination of physical and psychosocial stressors. The maternal separation model, where dams are separated from her pups for several hours per day during the postpartum period13,14, and the chronic social stress model, where the dams are exposed to a male intruder in the presence of their litters15,16, have been able to reproduce the emergence of abnormalities in maternal care and depressive-like phenotypes associated with physical stress paradigms. The chronic ultramild stress paradigm, where pregnant female mice are exposed to a variety of psychosocial insults, including cage tilt and overnight illumination, as well as substantial physiological insults, such as restraint stress and food restriction, has further revealed exposure to a mixed nature of stressors results in abnormalities in maternal behavior, including impairments in maternal aggression, as well as dysregulation in the circadian activity of the HPA axis17,18. Consistent with these results, an alternating restraint stress and overcrowding model during gestation results in elevations in postpartum maternal circadian corticosterone levels as well as alterations in maternal care, although no differences are observed in HPA axis re-activity following postpartum exposure to novel acute insults1.
An expansion of this work, generating a gestational stress paradigm that employs multiple psychosocial insults presented in an unpredictable fashion and minimizes the use of physiological stressors. Studies have previously shown this chronic psychosocial stress paradigm (CGS) results in the development of maternal HPA axis dysfunction, including enhanced stress reactivity in the early postpartum period19. These changes are associated with abnormalities in maternal behavior, including alterations in the quality of maternal care received by pups, and the emergence of anhedonic and anxiety-like behaviors19, features consistent with perinatal mood and anxiety disorders20,21. Furthermore, offspring weight gain reduces during the postnatal period following in-utero exposure to CGS19, suggesting CGS may have persistent negative programming effects in future generations.
The goal in developing the CGS paradigm was to primarily utilize clinically relevant stressors, which accurately capture the type, intensity, and frequency of insults often associated with neuroendocrine dysregulation and the development of perinatal mood and anxiety disorders. Here, the study provides a detailed protocol of how to subject pregnant female mice to CGS, as well as downstream assessments that can be used to test the validity of the model.

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	<tbody>
		<tr>
			<td>Animal lancet</td>
			<td>Braintree Scientific Inc.</td>
			<td>GR4MM</td>
			<td></td>
		</tr>
		<tr>
			<td>Blunt end probe</td>
			<td>Fine Science Tools</td>
			<td>10088-15</td>
			<td>Used to check for copulatory plugs</td>
		</tr>
		<tr>
			<td>Bottles for SPT</td>
			<td>Braintree Scientific Inc.</td>
			<td>WTRBTL S-BL</td>
			<td>100 mL glass water bottle with stopper and sipper ball point tube, graduted by 1 mL.</td>
		</tr>
		<tr>
			<td>Conical tubes (50 mL)</td>
			<td>Corning Inc.</td>
			<td>352098</td>
			<td>Used for restraining mice to measure HPA axis response to acute stress. Make sure conical tube has small opening at the end for ventilation.</td>
		</tr>
		<tr>
			<td>Legos</td>
			<td>Amazon</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Marbles</td>
			<td>Amazon</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse Corticosterone ELISA kit</td>
			<td>Biovendor</td>
			<td>RTC002R</td>
			<td></td>
		</tr>
		<tr>
			<td>Mouse EZM</td>
			<td>TSE Systems</td>
			<td>-</td>
			<td></td>
		</tr>
		<tr>
			<td>Reciprocal laboratory shaker</td>
			<td>Labnet international</td>
			<td>S2030-RC-B</td>
			<td></td>
		</tr>
		<tr>
			<td>Serum separator tubes</td>
			<td>Becton Dickinson</td>
			<td>365967</td>
			<td></td>
		</tr>
		<tr>
			<td>Static cage- bottom</td>
			<td>Alternative Design Manufacturing and Supply Inc.</td>
			<td>RC71D-PC</td>
			<td></td>
		</tr>
		<tr>
			<td>Static cage - filtered ventilated tops</td>
			<td>Alternative Design Manufacturing and Supply Inc.</td>
			<td>FT71H-PC</td>
			<td></td>
		</tr>
	</tbody>
</table>

using a murine model of psychosocial stress in pregnancy as a translationally relevant paradigm for psychiatric disorders in mothers and infants

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and offspring, including the development of neuropsychiatric disorders. Risk factors linked to the emergence of affective dysregulation in the maternal-infant dyad have been extensively studied. Exposure to psychosocial stress during pregnancy has consistently emerged as one of the strongest predictors. Several rodent models have been created to explore this association; however, these models rely on the use of physical stressors or a limited number of psychosocial stressors presented in a repetitive fashion, which do not accurately capture the type, intensity, and frequency of stressors experienced by women. To overcome these limitations, a chronic psychosocial stress (CGS) paradigm was generated that employs various psychosocial insults of different intensity presented in an unpredictable fashion. The manuscript describes this novel CGS paradigm where pregnant female mice, from gestational day 6.5 to 17.5, are exposed to various stressors during the day and overnight. Day stressors, two per day separated by a 2 h break, range from exposure to foreign objects or predator odor to frequent changes in bedding, removal of bedding, and cage tilting. Overnight stressors include continuous light exposure, changing cage mates, or wetting bedding. We have previously shown that exposure to CGS results in the development of maternal neuroendocrine and behavioral abnormalities, including increased stress reactivity, the emergence of fragmented maternal care patterns, anhedonia, and anxiety-related behaviors, core features of women suffering from perinatal mood and anxiety disorders. This CGS model, therefore, becomes a unique tool that can be used to elucidate molecular defects underlying maternal affective dysregulation, as well as trans-placental mechanisms that impact fetal neurodevelopment and result in negative long-term behavioral consequences in the offspring.

Exposing the pregnant female mice to CGS results in changes in chronic stress-relevant parameters, including a reduction in body weight gain during pregnancy (Figure 2A) and increased adrenal gland weights in the early postpartum period (Figure 2B)19. Importantly, exposure to CGS results in postpartum abnormalities in maternal neuroendocrine function. CGS dams exhibit a hyperactive HPA axis as evidenced by the increased serum corticostero...

Watch this Scientific Journal Video about Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants at JoVE.com

Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants

The chronic psychosocial stress (CGS) paradigm employs clinically relevant stressors during pregnancy in mice to model psychiatric disorders of mothers and infants. Here, we provide a step-by-step procedure of applying the CGS paradigm and downstream assessments to validate this model.

The peripartum period is considered a sensitive period where adverse maternal exposures can result in long-term negative consequences for both mother and ...

Our protocol is significant because it represents a new paradigm for evaluating the effects of chronic stress, specifically psychosocial stress, on pregnancy outcomes. In this protocol, we expose pregnant mice to various psychosocial insults of different intensities in an unpredictable fashion. Previous animal model paradigms employed physical stressors or a limited number of stressors administered repetitively, which does not reflect the experience of women during pregnancy.Our chronic psychosocial stress model overcomes these limitations. This method has wide ramifications for various research areas, including maternal mental health and adverse infant development-related research, and more broadly, for understanding the developmental origins of adult disease through adverse intrauterine events. Before starting each stressor in the CGS paradigm, bring the CGS group mice from the housing room into the room designated for CGS.Expose the mice to different stressors following an 11-day stressor regimen running from gestational day 6.5 to 17.5. To expose the mice to foreign objects, randomly distribute six marbles or six Legos of different shapes into a clean static cage with mouse bedding without the mouse nestlets. Place all mice from one home cage into the static cage with foreign objects for two hours, then return the mice to their home cage.To expose the mice to predator odor, place one centimeter thick dirty bedding from female rats into a clean static cage with no mouse bedding or nestlets. Place all mice from one home cage into the static cage with dirty rat bedding for two hours, then return the mice to their home cage. To expose the mice to a cage tilt, place all mice from one home cage into a clean static cage with mouse bedding without the mouse nestlets.Keep the cage tilted at a 30 degree angle against the wall for two hours, then return the mice to their home cage. To expose the mice to frequent bedding changes, place all mice from one home cage into a clean static cage with mouse bedding without the mouse nestlets. Every 10 minutes, gently move the mice to a different clean cage and replace the mouse bedding.After two hours, return the mice to their home cage. To expose the mice to bedding removal, place all mice from one home cage into an empty, clean static cage with no mouse bedding or nestlets for two hours, then return the mice to their home cage. To expose the mice to movement on a shaker, place all mice from one home cage into a clean static cage with mouse bedding without the mouse nestlets.Place the static cage atop a reciprocal lab shaker set to 140 strokes per minute for two hours, then return the mice to their home cage. To expose the mice to lights overnight, place all mice from one home cage into a clean static cage with mouse bedding without the mouse nestlets. Keep the lights on overnight to interfere with the dark cycle.On the following day, return the mice to their home cage. To expose a mouse to new cage mates, transfer the mouse into a clean static cage with mouse bedding containing two unfamiliar female mice. Leave the mouse in the static cage with the unfamiliar cage mates overnight.On the following day, returned the mouse to its home cage with familiar cage mates. To expose the mice to wet bedding, saturate the mouse bedding in a static cage with clean water kept at 24 degrees Celsius. Place all mice from one home cage into the static cage with wet bedding overnight.On the following day, return the mice to their home cage. After the stressor regimen is complete on gestational day 17.5, single house all the experimental mice to prepare for parturition and downstream functional assessments. Exposing pregnant female mice to CGS causes changes in chronic stress-relevant parameters, such as reduction in body weight gain during pregnancy and increased adrenal gland weights in the early postpartum period.Importantly, CGS dams exhibit postpartum abnormalities and maternal neuroendocrine function as evidenced by increased serum corticosterone levels following a novel acute insult. Furthermore, CGS dams display alterations in maternal care as reflected by an increase in the degree of fragmentation of maternal signals received by the pups. The average duration of licking/grooming bouts is reduced while the mean number of bouts is increased, indicating numerous short episodes of nurturing behavior.Sucrose preference is also depressed in CGS dams when compared to control dams, suggesting the presence of anhedonia. Lastly, the CGS dams also display increased anxiety-related behaviors as measured by a reduction in the time spent in the open quadrants of the EZM when compared to control dams. In the offspring, exposure to CGS in utero results in decreased weight gain during the postnatal period from postnatal day 7 to 21, although there are no differences at birth.This reduction in body weight gain is present in offspring of both sexes. When attempting this procedure, establishing a schedule for obtaining timed pregnancies and consistently implementing the entire series, variable unpredictable psychosocial stressors is critical. This technique can help answer interesting questions such as can maternal psychosocial stress cause sex-specific effects on placental function or offspring brain development and behavior?And can these effects be reversed or modified by pharmacological intervention or postnatal maternal care?

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Research

JoVE Journal

Behavior

The Resident-intruder Paradigm: A Standardized Test for Aggression, Violence and Social Stress

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression and defensive behavior in a semi natural setting. The most important behavioral elements performed by the resident and the intruder are demonstrated in the video and illustrated using artistic drawings. The use of the resident intruder paradigm for acute and chronic social stress experiments is explained as well. Finally, some brief tests and criteria are presented to distinguish aggression from its more violent and pathological forms.

This video shows the resident-intruder paradigm in rats. This test is a standardized method to measure offensive aggression, defensive behavior and violence in a semi-natural setting. The use of the paradigm for social stress experiments is explained as well.

This video publication explains in detail the experimental protocol of the resident-intruder paradigm in rats. This test is a standardized method to ...

P50 Sensory Gating in Infants

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood disorder, and schizophrenia. There has been increasing interest in the neurodevelopmental components of these attentional deficits; neurodevelopmental meaning that while the deficits become clinically prominent in childhood or adulthood, the deficits are the results of problems in brain development that begin in infancy or even prenatally. Despite this interest, there are few methods for assessing attention very early in infancy. This report focuses on one method, infant auditory P50 sensory gating.
Attention has several components. One of the earliest components of attention, termed sensory gating, allows the brain to tune out repetitive, noninformative sensory information. Auditory P50 sensory gating refers to one task designed to measure sensory gating using changes in EEG. When identical auditory stimuli are presented 500 ms apart, the evoked response (change in the EEG associated with the processing of the click) to the second stimulus is generally reduced relative to the response to the first stimulus (i.e. the response is &#34;gated&#34;). When response to the second stimulus is not reduced, this is considered a poor sensory gating, is reflective of impaired cerebral inhibition, and is correlated with attentional deficits.
Because the auditory P50 sensory gating task is passive, it is of potential utility in the study of young infants and may provide a window into the developmental time course of attentional deficits in a variety of neuropsychiatric disorders. The goal of this presentation is to describe the methodology for assessing infant auditory P50 sensory gating, a methodology adapted from those used in studies of adult populations.

Methods to record auditory P50 sensory gating, a physiological marker of cerebral inhibition which reflects early stages of attention, are described.

Attentional deficits are common in a variety of neuropsychiatric disorders including attention deficit-hyperactivity disorder, autism, bipolar mood ...

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals and humans. However, many animal models of depression were developed in males and are not applicable or effective in studies of postpartum females. Recent studies have reported significant effects of chronic social stress during lactation, an ethologically relevant and effective stressor, on maternal behavior, growth, and behavioral neuroendocrinology. This manuscript will describe this chronic social stress paradigm using repeated exposure of a lactating dam to a novel male intruder, and the assessment of the behavioral, physiological, and neuroendocrine effects of this model. Chronic social stress (CSS) is a valuable model for studying the effects of stress on the behavior and physiology of the dam as well as her offspring and future generations. The exposure of pups to CSS can also be used as an early life stress that has long term effects on behavior, physiology, and neuroendocrinology.

This article describes the use of chronic resident intruder social stress as an ethologically relevant paradigm to model postpartum depression and anxiety in lactating rodents.

Exposure to chronic stress is a reliable predictor of depressive disorders, and social stress is a common ethologically relevant stressor in both animals ...

The Crossmodal Congruency Task as a Means to Obtain an Objective Behavioral Measure in the Rubber Hand Illusion Paradigm

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden hand is touched. If the viewed and felt touches are given at the same time then this is sufficient to induce the compelling experience that the rubber hand is one's own hand. The RHI can be used to investigate exactly how the brain constructs distinct body representations for one's own body. Such representations are crucial for successful interactions with the external world. To obtain a subjective measure of the RHI, researchers typically ask participants to rate statements such as "I felt as if the rubber hand were my hand". Here we demonstrate how the crossmodal congruency task can be used to obtain an objective behavioral measure within this paradigm.
The variant of the crossmodal congruency task we employ involves the presentation of tactile targets and visual distractors. Targets and distractors are spatially congruent (i.e. same finger) on some trials and incongruent (i.e. different finger) on others. The difference in performance between incongruent and congruent trials - the crossmodal congruency effect (CCE) - indexes multisensory interactions. Importantly, the CCE is modulated both by viewing a hand as well as the synchrony of viewed and felt touch which are both crucial factors for the RHI.
The use of the crossmodal congruency task within the RHI paradigm has several advantages. It is a simple behavioral measure which can be repeated many times and which can be obtained during the illusion while participants view the artificial hand. Furthermore, this measure is not susceptible to observer and experimenter biases. The combination of the RHI paradigm with the crossmodal congruency task allows in particular for the investigation of multisensory processes which are critical for modulations of body representations as in the RHI.

We demonstrate how an objective measure can be employed in the widely employed rubber hand illusion paradigm. This measure is obtained by modifying the well-established crossmodal congruency task. This task allows the investigation of multisensory processes which are critical for modulations of body representations as in the rubber hand illusion.

The rubber hand illusion (RHI) is a popular experimental paradigm. Participants view touch on an artificial rubber hand while the participants' own hidden ...

Assessment of Age-related Changes in Cognitive Functions Using EmoCogMeter, a Novel Tablet-computer Based Approach

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognitive functions across the lifespan in a sample of 378 healthy subjects (age range 18-89 years). Consistent with previous findings we found an age-related cognitive decline across a wide range of neuropsychological domains (memory, attention, executive functions), thereby proving the usability of our tablet-based application. Regardless of prior computer experience, subjects of all age groups were able to perform the tasks without instruction or feedback from an experimenter. Increased motivation and compliance proved to be beneficial for task performance, thereby potentially increasing the validity of the results. Our promising findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

We tested the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on cognition. Results show an age-related cognitive decline, thereby proving the usability of our application. Findings underline the great clinical and practical potential of a tablet-based application for detection and monitoring of cognitive dysfunction.

The main goal of this study was to assess the usability of a tablet-computer-based application (EmoCogMeter) in investigating the effects of age on ...

A Cognitive Paradigm to Investigate Interference in Working Memory by Distractions and Interruptions

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that one attempts to ignore, or by interrupting information that demands attention as part of another (secondary) task goal. Both forms of external interference have been shown to detrimentally impact the ability to maintain information in working memory (WM). Emerging evidence suggests that these different types of external interference exert different effects on behavior and may be mediated by distinct neural mechanisms. Better characterizing the distinct neuro-behavioral impact of irrelevant distractions versus attended interruptions is essential for advancing an understanding of top-down attention, resolution of external interference, and how these abilities become degraded in healthy aging and in neuropsychiatric conditions. This manuscript describes a novel cognitive paradigm developed the Gazzaley lab that has now been modified into several distinct versions used to elucidate behavioral and neural correlates of interference, by to-be-ignored distractors versus to-be-attended interruptors. Details are provided on variants of this paradigm for investigating interference in visual and auditory modalities, at multiple levels of stimulus complexity, and with experimental timing optimized for electroencephalography (EEG) or functional magnetic resonance imaging (fMRI) studies. In addition, data from younger and older adult participants obtained using this paradigm is reviewed and discussed in the context of its relationship with the broader literatures on external interference and age-related neuro-behavioral changes in resolving interference in working memory.

A novel cognitive paradigm is developed to elucidate behavioral and neural correlates of interference by to-be-ignored distractors versus interference by to-be-attended interruptors during a working memory task. In this manuscript, several variants of this paradigm are detailed, and data obtained with this paradigm in younger/older adult participants is reviewed.

Goal-directed behavior is often impaired by interference from the external environment, either in the form of distraction by irrelevant information that ...

Vagus Nerve Stimulation as a Tool to Induce Plasticity in Pathways Relevant for Extinction Learning

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been maintaining the behavior. There is close correspondence between fear and human anxiety, and therefore studies of extinction learning might provide insight into the biological nature of anxiety-related disorders such as post-traumatic stress disorder, and they might help to develop strategies to treat them. Preclinical research aims to aid extinction learning and to induce targeted plasticity in extinction circuits to consolidate the newly formed memory. Vagus nerve stimulation (VNS) is a powerful approach that provides tight temporal and circuit-specific release of neurotransmitters, resulting in modulation of neuronal networks engaged in an ongoing task. VNS enhances memory consolidation in both rats and humans, and pairing VNS with exposure to conditioned cues enhances the consolidation of extinction learning in rats. Here, we provide a detailed protocol for the preparation of custom-made parts and the surgical procedures required for VNS in rats. Using this protocol we show how VNS can facilitate the extinction of conditioned fear responses in an auditory fear conditioning task. In addition, we provide evidence that VNS modulates synaptic plasticity in the pathway between the infralimbic (IL) medial prefrontal cortex and the basolateral complex of the amygdala (BLA), which is involved in the expression and modulation of extinction memory.

Vagus nerve stimulation (VNS) has emerged as a tool to induce targeted synaptic plasticity in the forebrain to modify a range of behaviors. This protocol describes how to implement VNS to facilitate the consolidation of fear extinction memory.

Extinction describes the process of attenuating behavioral responses to neutral stimuli when they no longer provide the reinforcement that has been ...

The Social Dimension of Stress: Experimental Manipulations of Social Support and Social Identity in the Trier Social Stress Test

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations supportive behavior of other people as well as positive social relationships can act as powerful resources to cope with stress. In order to study the interplay between these variables, this protocol describes two effective experimental manipulations of social relationships and supportive behavior in the laboratory. In the present article, these two manipulations are implemented in the Trier Social Stress Test (TSST)&#8212;a standard stress induction paradigm in which participants are subjected to a simulated job interview. More precisely, we propose (a) a manipulation of the relationship between different protagonists in the TSST by making a shared social identity salient and (b) a manipulation of the behavior of the TSST-selection committee, which acts either supportively or unsupportively. These two experimental manipulations are designed in a modular fashion and can be applied independently of each other but can also be combined. Moreover, these two manipulations can also be integrated into other stress protocols and into other standardized social interactions such as trust games, negotiation tasks, or other group tasks.

Previous research on the social dimension of stress has focused on two important variables: social identity and social support. This protocol introduces an effective experimental manipulation of these two social variables and describes their implementation in a standard stress induction paradigm (Trier Social Stress Test).

In many situations humans are influenced by the behavior of other people and their relationships with them. For example, in stressful situations ...

Ultrasound Images of the Tongue: A Tutorial for Assessment and Remediation of Speech Sound Errors

Diagnostic ultrasound imaging has been a common tool in medical practice for several decades. It provides a safe and effective method for imaging structures internal to the body. There has been a recent increase in the use of ultrasound technology to visualize the shape and movements of the tongue during speech, both in typical speakers and in clinical populations. Ultrasound imaging of speech has greatly expanded our understanding of how sounds articulated with the tongue (lingual sounds) are produced. Such information can be particularly valuable for speech-language pathologists. Among other advantages, ultrasound images can be used during speech therapy to provide (1) illustrative models of typical (i.e.&#160;&#34;correct&#34;) tongue configurations for speech sounds, and (2) a source of insight into the articulatory nature of deviant productions. The images can also be used as an additional source of feedback for clinical populations learning to distinguish their better productions from their incorrect productions, en route to establishing more effective articulatory habits.
Ultrasound feedback is increasingly used by scientists and clinicians as both the expertise of the users increases and as the expense of the equipment declines. In this tutorial, procedures are presented for collecting ultrasound images of the tongue in a clinical context. We illustrate these procedures in an extended example featuring one common error sound, American English /r/. Images of correct and distorted /r/ are used to demonstrate (1) how to interpret ultrasound images, (2) how to assess tongue shape during production of speech sounds, (3), how to categorize tongue shape errors, and (4), how to provide visual feedback to elicit a more appropriate and functional tongue shape. We present a sample protocol for using real-time ultrasound images of the tongue for visual feedback to remediate speech sound errors. Additionally, example data are shown to illustrate outcomes with the procedure.

Ultrasound imaging can be used to display the shape and movements of the tongue in real time during speech. The images can be used to determine the nature of speech sound errors. Visual feedback of the tongue can be used to facilitate improvements in speech sound production in clinical populations.

Diagnostic ultrasound imaging has been a common tool in medical practice for several decades. It provides a safe and effective method for imaging ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits the evaluation of the conditioned rewarding effects of drugs related to environmental cues. Then, the extinguished CPP can be robustly reinstated by the non-contingent administration of a priming dose of the drug, and by exposure to stressful stimuli. Both methods will be explained here. When the animal reinitiates the behavioral response, a reinstatement of the conditioned reward is considered to have taken place.
The main advantages of this protocol are that it is non-invasive, inexpensive, and simple with good validity criteria. In addition, it allows the study of different environmental manipulations, such as stress or diet, which can modulate relapse into drug seeking behaviors. However, one limitation is that if the researcher aims to explore the motivation and primary reinforcing effects of the drug, it should be complemented with self-administration procedures, as they involve operant responses of animals.

This protocol describes the Conditioned Place Preference (CPP) as a model of relapse. This procedure permits the measurement of relapse in laboratory animals, considering the impact of drug-associated environmental cues as craving and relapse in abstaining addicts is currently the focus of drug-abuse treatment programs.

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...