A Neural Switch for Active and Passive Fear

Gozzi, Alessandro; Jain, Apar; Giovanelli, A.; Bertollini, Cristina; Crestan, Valerio; Schwarz, Adam J.; Tsetsenis, Theodoros; Ragozzino, Davide; Gross, Cornelius; Bifone, Angelo

doi:10.1016/j.neuron.2010.07.008

Cited by 185 publications

(104 citation statements)

References 37 publications

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“…Alternatively, or additionally, Rapid Avoiders may have enhanced motivational control of instrumental performance, or enhanced reward processing, perhaps due to more efficient neural interactions between the amygdala and nucleus accumbens (Cain and LeDoux, 2008; Boschen et al, 2011). Rapid Avoiders may also more rapidly link defensive organismic states to action, which could stem from more efficient amygdala CeA connections with cholinergic forebrain targets, previously shown to contribute to active responses to threats (Gozzi et al, 2010). It is also possible that in extremely rapid AA acquisition, where escape is reflexively elicited as soon as a route is provided, without initial freezing, escape may more closely approximate an innate survival circuit response.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues

Galatzer‐Levy

Moscarello

Blessing

et al. 2014

Front. Syst. Neurosci.

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Individuals exposed to traumatic stressors follow divergent patterns including resilience and chronic stress. However, researchers utilizing animal models that examine learned or instrumental threat responses thought to have translational relevance for Posttraumatic Stress Disorder (PTSD) and resilience typically use central tendency statistics that assume population homogeneity. This approach potentially overlooks fundamental differences that can explain human diversity in response to traumatic stressors. The current study tests this assumption by identifying and replicating common heterogeneous patterns of response to signaled active avoidance (AA) training. In this paradigm, rats are trained to prevent an aversive outcome (shock) by performing a learned instrumental behavior (shuttling between chambers) during the presentation of a conditioned threat cue (tone). We test the hypothesis that heterogeneous trajectories of threat avoidance provide more accurate model fit compared to a single mean trajectory in two separate studies. Study 1 conducted 3 days of signaled AA training (n = 81 animals) and study 2 conducted 5 days of training (n = 186 animals). We found that four trajectories in both samples provided the strongest model fit. Identified populations included animals that acquired and retained avoidance behavior on the first day (Rapid Avoiders: 22 and 25%); those who never successfully acquired avoidance (Non-Avoiders; 20 and 16%); a modal class who acquired avoidance over 3 days (Modal Avoiders; 37 and 50%); and a population who demonstrated a slow pattern of avoidance, failed to fully acquire avoidance in study 1 and did acquire avoidance on days 4 and 5 in study 2 (Slow Avoiders; 22.0 and 9%). With the exception of the Slow Avoiders in Study 1, populations that acquired demonstrated rapid step-like increases leading to asymptotic levels of avoidance. These findings indicate that avoidance responses are heterogeneous in a way that may be informative for understanding both resilience and PTSD as well as the nature of instrumental behavior acquisition. Characterizing heterogeneous populations based on their response to threat cues would increase the accuracy and translatability of such models and potentially lead to new discoveries that explain diversity in instrumental defensive responses.

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Section: Discussionmentioning

confidence: 99%

Heterogeneity in signaled active avoidance learning: substantive and methodological relevance of diversity in instrumental defensive responses to threat cues

Galatzer‐Levy

Moscarello

Blessing

et al. 2014

Front. Syst. Neurosci.

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“…Several theories of fear refer to the coexistence of different coping strategies, or ‘styles’, which induce specific types of responses to threatening situations; these are usually classified as passive (or reactive) and active (or proactive) 102,103 . Another distinct feature of the eCB system is its role in the regulation of switching between these different strategies, that is, between a passive fear response (such as freezing) and active behaviours (such as escape attempts and risk assessment).…”

Section: Fear-coping Strategiesmentioning

confidence: 99%

The endocannabinoid system in guarding against fear, anxiety and stress

et al. 2015

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The endocannabinoid (eCB) system has emerged as a central integrator linking the perception of external and internal stimuli to distinct neurophysiological and behavioural outcomes (such as fear reaction, anxiety and stress-coping), thus allowing an organism to adapt to its changing environment. eCB signalling seems to determine the value of fear-evoking stimuli and to tune appropriate behavioural responses, which are essential for the organism’s long-term viability, homeostasis and stress resilience; and dysregulation of eCB signalling can lead to psychiatric disorders. An understanding of the underlying neural cell populations and cellular processes enables the development of therapeutic strategies to mitigate behavioural maladaptation.

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“…A recent study [51] has significantly expanded the area of application of these methods, by providing a remarkable example of the use of phMRI, intersubject functional connectivity and advanced mouse genetics to provide a direct link between cells, circuits and behavior. Specifically, the authors combined phMRI and focal pharmacogenetic silencing to spatially resolve behavior-specific circuits controlled by a discrete neuronal population expressed in the central nucleus of the amygdala (CeA), a brain region involved in the control of emotional and behavioral response to fear [52].…”

Section: Application To Mapping Functional Connectivity In Neurotransmentioning

confidence: 99%