Cognitive dysfunctions are commonly seen in many stress-related disorders, including
anxiety and depression&#x2014;the world&#x27;s most common neuropsychiatric illnesses. Various genetic,
pharmacological, and behavioral animal models have long been used to establish animal anxiety-like
and depression-like phenotypes, as well as to assess their memory, learning, and other
cognitive functions. Mounting clinical and animal evidences strongly supports the notion that
disturbed cognitions represent an important pathogenetic factor in anxiety and depression, and may
also play a role in integrating the two disorders within a common stress-precipitated
developmental pathway. This paper evaluates why and how the assessment of cognitive and
emotional domains may improve our understanding of animal behaviors via different high-throughput
tests and enable a better translation of animal phenotypes into human brain disorders.

Allan V. Kalueff

Dennis L. Murphy

The Importance of Cognitive Phenotypes in Experimental Modeling of Animal Anxiety and Depression

Patrice Venault

Georges Chapouthier

Plasticity and Anxiety

Anxiety is most common among Alzheimer&#x27;s disease (AD) patients with an age
at onset under age 65. Apolipoprotein E4 (apoE4) is a risk factor for
developing AD at an earlier age and might contribute to this effect. In
mice, apoE plays a role in the regulation of anxiety, which might involve
histamine receptor-mediated signaling and steroidogenesis in the adrenal
gland. In addition, human apoE isoforms have differential effects on anxiety
in adult mice lacking apoE and probable AD patients. Compared to wild-type
mice, mice lacking apoE and apoE4 mice showed pathological alterations in
the central nucleus of the amygdala, which is involved in regulation of
anxiety. ApoE4, but not mice lacking apoE, or apoE3 mice showed impaired
dexamethasone suppression of plasma corticosterone. Understanding how apoE
modulates measures of anxiety might help the developments of therapeutic
targets to reduce or even prevent measures of anxiety in health and in
dementing illnesses.

Jacob Raber

Role of Apolipoprotein E in Anxiety

We describe a new arachnophobia therapy that is specially suited for those individuals with severe arachnophobia who are reluctant to undergo direct or even virtual exposure treatments. In this therapy, patients attend a computer presentation of images that, while not being spiders, have a subset of the characteristics of spiders. The Atomium of Brussels is an example of such an image. The treatment group (<mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>13</mml:mn></mml:math>) exhibited a significant improvement 
(time <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>&#x00D7;</mml:mo></mml:math> group interaction: <mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi><mml:mo>=</mml:mo><mml:mn>.0026</mml:mn></mml:math>) when compared to the placebo group 
(<mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>n</mml:mi><mml:mo>=</mml:mo><mml:mn>12</mml:mn></mml:math>) in a repeated measures multivariate ANOVA. 
A <mml:math id="E5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>k</mml:mi></mml:math>-means clustering algorithm revealed that, after 4 weeks of treatment, 42&#x25; of the patients moved from the arachnophobic to the nonarachnophobic cluster. Six months after concluding the treatment, a follow-up study showed a substantial consolidation of the recovery process where 92&#x25; of the arachnophobic patients moved to the nonarachnophobic cluster.

Laura Carmilo Granado

Ronald Ranvaud

Javier Ropero Pel&#xE1;ez

A Spiderless Arachnophobia Therapy: Comparison between Placebo and Treatment Groups and Six-Month Follow-Up Study

The endocannabinoid system has been involved in the regulation of anxiety, and proposed as an inhibitory modulator of neuronal, behavioral and adrenocortical responses to stressful stimuli. Brain regions such as the amygdala, hippocampus and cortex, which are directly involved in the regulation of emotional behavior, contain high densities of cannabinoid CB1 receptors. Mutant mice lacking CB1 receptors show anxiogenic and depressive-like behaviors as well as an altered hypothalamus pituitary adrenal axis activity, whereas enhancement of endocannabinoid signaling produces anxiolytic and antidepressant-like effects. Genetic and pharmacological approaches also support an involvement of endocannabinoids in extinction of aversive memories. Thus, the endocannabinoid system appears to play a pivotal role in the regulation of emotional states. Endocannabinoids have emerged as mediators of short- and long- term synaptic plasticity in diverse brain structures. Despite the fact that most of the studies on this field have been performed using in vitro models, endocannabinoid-mediated plasticity might be considered as a plausible candidate underlying some of the diverse physiological functions of the endogenous cannabinoid system, including developmental, affective and cognitive processes. In this paper, we will focus on the functional relevance of endocannabinoid-mediated plasticity within the framework of emotional responses. Alterations of the endocannabinoid system may constitute an important factor in the aetiology of certain neuropsychiatric disorders, and, in turn, enhancers of endocannabinoid signaling could represent a potential therapeutical tool in the treatment of both anxiety and depressive symptoms.

Mar&#xED;a-Paz Viveros

Eva-Mar&#xED;a Marco

Ricardo Llorente

Meritxell L&#xF3;pez-Gallardo

Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

High concentrations of pituitary adenylate cyclase-activating polypeptide (PACAP) 
            nerve fibers are present in the central nucleus of amygdala (CeA), a brain region implicated 
            in the control of fear-related behavior. This study evaluated PACAPergic modulation of fear 
            responses at the CeA in male Sprague-Dawley rats. PACAP (50&#x2013;100 &#x2009; pmol) 
            microinfusion  via intra-CeA cannulae produced increases in immobility and time the rats 
            spent withdrawn into a corner opposite to the electrified probe compared to controls in the 
            shock-probe fear/defensive burying test. Shock-probe burying and exploration, numbers 
            of shocks received, locomotion distance, and velocity were all reduced by intra-CeA PACAP 
            injection. Further, intra-CeA PACAP effects were manifested only when the animals were 
            challenged by shock, as intra-CeA PACAP injections did not cause significant changes 
            in the behaviors of unshocked rats. Thus, intra-CeA 
            administration of PACAP produces a distinct reorganization of stress-coping behaviors from 
            active (burying) to passive modes, such as withdrawal and immobility. These findings are 
            potentially significant toward enhancing our understanding of the involvement of PACAP 
            and the CeA in the neural basis of fear and anxiety.

Gabor Legradi

Mahasweta Das

Brian Giunta

Khemraj Hirani

E. Alice Mitchell

David M. Diamond

Microinfusion of Pituitary Adenylate Cyclase-Activating Polypeptide into the Central Nucleus of Amygdala of the Rat Produces a Shift from an Active to Passive Mode of Coping in the Shock-Probe Fear/Defensive Burying Test

A phylogenetic approach to anxiety is proposed. The different facets of human anxiety and their presence at different levels of the phylum are examined. All organisms, including unicellular such as protozoan, can display a specific reaction to danger. The mechanisms enabling the appraisal of harmful stimuli are fully present in insects. In higher invertebrates, fear is associated with a specific physiological response. In mammals, anxiety is accompanied by specific cognitive responses. The expression of emotions diversifies in higher vertebrates, only primates displaying facial expressions. Finally, autonoetic consciousness, a feature essential for human anxiety, appears only in great apes. This evolutive feature parallels the progress in the complexity of the logistic systems supporting it (e.g., the vegetative and central nervous systems). The ability to assess one&#x27;s coping potential, the diversification of the anxiety responses, and autonoetic consciousness seem relevant markers in a phylogenetic perspective.

Catherine Belzung

Pierre Philippot

Anxiety from a Phylogenetic Perspective: Is there a Qualitative Difference between Human and Animal Anxiety&#x3F;

There is a growing body of evidence that neural stem cells reside in the adult central 
	nervous system where neurogenesis occurs throughout lifespan. Neurogenesis concerns 
	mainly two areas in the brain: the subgranular zone of the dentate gyrus in the hippocampus 
	and the subventricular zone, where it is controlled by several trophic factors and neuroactive 
	molecules. Neurogenesis is involved in processes such as learning and memory and 
	accumulating evidence implicates hippocampal neurogenesis in the physiopathology of 
	depression. We herein review experimental and clinical data demonstrating that stress 
	and antidepressant treatments affect neurogenesis in opposite direction in rodents. 
	In particular, the stimulation of hippocampal neurogenesis by all types of antidepressant drugs 
	supports the view that neuroplastic phenomena are involved in the physiopathology of 
	depression and underlie&#8212;at least partly&#8212;antidepressant therapy.

Eleni  Paizanis

Michel  Hamon

Laurence  Lanfumey

Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

Stress is a potent modulator of learning and memory processes. Although there have been a few attempts in the literature to explain the diversity of effects (including facilitating, impairing, and lack of effects) described for the impact of stress on memory function according to single classification criterion, they have proved insufficient to explain the whole complexity of effects. Here, we review the literature in the field of stress and memory interactions according to five selected classifying factors (source of stress, stressor duration, stressor intensity, stressor timing with regard to memory phase, and learning type) in an attempt to develop an integrative model to understand how stress affects memory function. Summarizing on those conditions in which there was enough information, we conclude that high stress levels, whether intrinsic (triggered by the cognitive challenge) or extrinsic (induced by conditions completely unrelated to the cognitive task), tend to facilitate Pavlovian conditioning (in a linear-asymptotic manner), while being deleterious for spatial/explicit information processing (which with regard to intrinsic stress levels follows an inverted U-shape effect). Moreover, after reviewing the literature, we conclude that all selected factors are essential to develop an integrative model that defines the outcome of stress effects in memory processes. In parallel, we provide a brief review of the main neurobiological mechanisms proposed to account for the different effects of stress in memory function. Glucocorticoids were found as a common mediating mechanism for both the facilitating and impairing actions of stress in different memory processes and phases. Among the brain regions implicated, the hippocampus, amygdala, and prefrontal cortex were highlighted as critical for the mediation of stress effects.

Carmen Sandi

M. Teresa Pinelo-Nava

Stress and Memory: Behavioral Effects and Neurobiological Mechanisms

Corticosteroids regulate stress response and influence emotion, learning, and memory via two receptors in the brain, the high&#x2010;affinity mineralocorticoid (MR) and low&#x2010;affinity glucocorticoid receptor (GR). We test the hypothesis that MR- and GR-mediated effects interact in emotion and cognition when a novel situation is encountered that is relevant for a learning process. By adrenalectomy and additional constant corticosterone supplement we obtained four groups of male C57BL/6J mice with differential chronic MR and GR activations. Using a hole board task, we found that mice with continuous predominant MR and moderate GR activations were fast learners that displayed low anxiety and arousal together with high directed explorative behavior. Progressive corticosterone concentrations with predominant action via GR induced strong emotional arousal at the expense of cognitive performance. These findings underline the importance of a balanced MR/GR system for emotional and cognitive functioning that is critical for mental health.

Vera Brinks

Maaike H. van der Mark

E. Ron de Kloet

Melly S. Oitzl

Differential MR/GR Activation in Mice Results in Emotional States Beneficial or Impairing for Cognition

About this journal

Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

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Chief Editor, Professor Baudry, is currently University Professor at Western University of Health Sciences in Pomona, CA. His research focuses on understanding the molecular/cellular mechanisms of learning and memory and neurodegeneration.

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Neural Plasticity is an interdisciplinary journal dedicated to the publication of articles related to all aspects of neural plasticity, with special emphasis on its functional significance as reflected in behavior and in psychopathology.

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Neural Plasticity | Hindawi

Neural Plasticity

This Issue is now open for submissions.
Papers are published upon acceptance, regardless of the Special Issue publication date.

Neural Plasticity

Plasticity and Anxiety

Plasticity and Anxiety

Articles

The Importance of Cognitive Phenotypes in Experimental Modeling of Animal Anxiety and Depression

Plasticity and Anxiety

Role of Apolipoprotein E in Anxiety

A Spiderless Arachnophobia Therapy: Comparison between Placebo and Treatment Groups and Six-Month Follow-Up Study

Endocannabinoid System and Synaptic Plasticity: Implications for Emotional Responses

Microinfusion of Pituitary Adenylate Cyclase-Activating Polypeptide into the Central Nucleus of Amygdala of the Rat Produces a Shift from an Active to Passive Mode of Coping in the Shock-Probe Fear/Defensive Burying Test

Anxiety from a Phylogenetic Perspective: Is there a Qualitative Difference between Human and Animal Anxiety?

Hippocampal Neurogenesis, Depressive Disorders, and Antidepressant Therapy

Stress and Memory: Behavioral Effects and Neurobiological Mechanisms

Differential MR/GR Activation in Mice Results in Emotional States Beneficial or Impairing for Cognition