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

We have reviewed research on the effects of stress on LTP in the hippocampus, amygdala and prefrontal cortex (PFC) and present new findings which provide insight into how the attention and memory-related functions of these structures are influenced by strong emotionality. We have incorporated the stress-LTP findings into our &#8220;temporal dynamics&#8221; model, which provides a framework for understanding the neurobiological basis of flashbulb and traumatic memories, as well as stress-induced amnesia. An important feature of the model is the idea that endogenous mechanisms of plasticity in the hippocampus and amygdala are rapidly activated for a relatively short period of time by a strong emotional learning experience. Following this activational period, both structures undergo a state in which the induction of new plasticity is suppressed, which facilitates the memory consolidation process. We further propose that with the onset of strong emotionality, the hippocampus rapidly shifts from a &#8220;configural/cognitive map&#8221; mode to a &#8220;flashbulb memory&#8221; mode, which underlies the long-lasting, but fragmented, nature of traumatic memories. Finally, we have speculated on the significance of stress-LTP interactions in the context of the Yerkes-Dodson Law, a well-cited, but misunderstood, century-old principle which states that the relationship between arousal and behavioral performance can be linear or curvilinear, depending on the difficulty of the task.

David M. Diamond

Adam M. Campbell

Collin R. Park

Joshua  Halonen

Phillip R. Zoladz

The Temporal Dynamics Model of Emotional Memory Processing: A Synthesis on the Neurobiological  Basis of Stress-Induced Amnesia, Flashbulb and Traumatic Memories, and the Yerkes-Dodson Law

Two principal component analyses of anxiety were undertaken investigating
two strains of mice (ABP/Le and C57BL/6ByJ) in two different experiments,
both classical tests for assessing anxiety in rodents. The elevated
plus-maze and staircase were used for the first experiment, and a free
exploratory paradigm and light-dark discrimination were used for the second.
The components in the analyses produced definitions of four fundamental
behavior patterns: novelty-induced anxiety, general activity, exploratory
behavior, and decision making. We also noted that the anxious phenotype was
determined by both strain and experimental procedure. The relationship
between behavior patterns and the use of specific tests plus links with the
genetic background are discussed.

Yan Cl&#xe9;ment

Chantal Joubert

Caroline Kopp

Eve M. Lepicard

Patrice Venault

Ren&#xe9; Misslin

Martine Cadot

Georges Chapouthier

Anxiety in Mice: A Principal Component Analysis Study

When an organism is exposed to a stressful situation, corticosteroid levels in the brain rise. This rise has consequences for behavioral performance, including memory formation. Over the past decades, it has become clear that a rise in corticosteroid level is also accompanied by a reduction in hippocampal long-term potentiation (LTP). Recent studies, however, indicate that stress does not lead to a universal suppression of LTP. Many factors, including the type of stress, the phase of the stress response, the area of investigation, type of LTP, and the life history of the organism determine in which direction LTP will be changed.

Marian  Jo&#235;ls

Harm J. Krugers

LTP after Stress: Up or Down&#63;

Stress exposure, depending on its intensity and duration, affects cognition and learning in an adaptive or maladaptive manner. Studies addressing the effects of stress on cognitive processes have mainly focused on conditioned fear, since it is suggested that fear-motivated learning lies at the root of affective and anxiety disorders. Inhibition of fear-motivated response can be accomplished by experimental extinction of the fearful response to the fear-inducing stimulus. Converging evidence indicates that extinction of fear memory requires plasticity in both the medial prefrontal cortex and the amygdala. These brain areas are also deeply involved in mediating the effects of exposure to stress on memory. Moreover, extensive evidence indicates that gamma-aminobutyric acid (GABA) transmission plays a primary role in the modulation of behavioral sequelae resulting from a stressful experience, and may also partially mediate inhibitory learning during extinction. In this review, we present evidence that exposure to a stressful experience may impair fear extinction  and the possible involvement of the GABA system. Impairment of fear extinction learning is particularly important as it may predispose some individuals to the development of posttraumatic stress disorder. We further discuss a possible dysfunction in the medial prefrontal cortex-amygdala circuit following a stressful experience that may explain the impaired extinction caused by exposure to a stressor.

Irit Akirav

Mouna Maroun

The Role of the Medial Prefrontal Cortex-Amygdala Circuit in Stress Effects on the Extinction of Fear

Interaction of anxiety and memory represents an essential feature of CNS functioning. This paper reviews experimental data coming from neurogenetics, neurochemistry, and behavioral pharmacology (as well as parallel clinical findings) reflecting different mechanisms of memory-anxiety interplay, including brain neurochemistry, circuitry, pharmacology, neuroplasticity, genes, and gene-environment interactions. It emphasizes the complexity and nonlinearity of such interplay, illustrated by a survey of anxiety and learning/memory phenotypes in various genetically modified mouse models that exhibit either synergistic or reciprocal effects of the mutation on anxiety levels and memory performance. The paper also assesses the putative role of different neurotransmitter systems and neuropeptides in the regulation of memory processes and anxiety, and discusses the role of neural plasticity in these mechanisms.

Allan V. Kalueff

Neurobiology of Memory and Anxiety: From Genes to Behavior

Memory consolidation requires synaptic reconfiguration dependent upon extracellular matrix (ECM) 
molecules interacting with cell adhesion molecules. Matrix metalloproteinase (MMP) activity is responsible 
for transient alterations in the ECM that may be prerequisite to hippocampal-dependent learning. In support
 of this hypothesis we have measured increases in MMP-3 and MMP-9 levels within the hippocampus and 
 prefrontal cortex during Morris water maze training. The present investigation extends these findings by 
 determining that infusion of an MMP inhibitor (FN-439) into the dorsal hippocampus disrupted acquisition 
 of this task. In vitro fluorescence enzyme assays to determine the specificity of FN-439 
 against the catalytic domains of MMP-3 and MMP-9 indicated mean <mml:math id="E1" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>&#x00B1;</mml:mo></mml:math> SEM <mml:math id="E2" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mrow><mml:msub><mml:mrow><mml:mtext>IC</mml:mtext></mml:mrow><mml:mrow><mml:mn>50</mml:mn></mml:mrow></mml:msub><mml:mtext>s</mml:mtext></mml:mrow></mml:math> of 16.2 <mml:math id="E3" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>&#x00B1;</mml:mo></mml:math> 7.8 and 210.5 <mml:math id="E4" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mo>&#x00B1;</mml:mo></mml:math> 37.8 <mml:math id="E5" xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>&#x03BC;</mml:mi></mml:math>M, 
 respectively, while in situ zymography using hippocampal sections treated with FN-439 indicated significant 
 reductions in MMP gelatinase activity. These results suggest that compromising the ability of the dorsal 
 hippocampus to reconfigure ECM molecules by inhibiting MMP activity interferes with appropriate spatial 
 memory acquisition, and support a role for hippocampal MMPs in the phenomena of spatial memory acquisition 
 and storage.

John W. Wright

Travis E. Brown

Joseph W. Harding

Inhibition of Hippocampal Matrix Metalloproteinase-3 and -9 Disrupts Spatial Memory

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 - Table of contents 2007

title

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.

Neural Plasticity