Effect of repeated seizures on spatial exploration and immediate early gene expression in the hippocampus and dentate gyrus.

Immediate early genes (IEGs) are coordinately activated in response to neuronal activity and can cause activation of secondary response genes that modulate synaptic plasticity and mediate long-lasting changes in behaviour. Excessive neuronal stimulation induced by epileptic seizures induce rapid and dramatic changes in IEG expression. Although the impact of acute seizure activity on IEG expression has been well studied, less is known about the long-term effects of chronic seizures on IEG induction during seizure free periods where behavioural and cognitive impairments are frequently observed in people with epilepsy and in animal models of epilepsy.

Distributed learning episodes create a context fear memory outside the hippocampus that depends on perirhinal and anterior cingulate cortices.

Damage to the hippocampus (HPC) typically causes retrograde amnesia for contextual fear conditioning. Repeating the conditioning over several sessions, however, can eliminate the retrograde amnesic effects. This form of reinstatement thus permits modifications to networks that can support context memory retrieval in the absence of the HPC.

Prelimbic cortex glucocorticoid receptors regulate the stress-mediated inhibition of pain contagion in male mice.

Experiencing pain with a familiar individual can enhance one's own pain sensitivity, a process known as pain contagion. When experiencing pain with an unfamiliar individual, pain contagion is suppressed in males by activating the endocrine stress response. Here, we coupled a histological investigation with pharmacological and behavioral experiments to identify enhanced glucocorticoid receptor activity in the prelimbic subdivision of the medial prefrontal cortex as a candidate mechanism for suppressing pain contagion in stranger mice.

The effect of left and right long-term amygdala kindling on interictal emotionality and Fos expression.

Clinical observations have often reported that patients with seizures arising from limbic structures on the right side of the brain have a higher incidence of emotional disturbances, such as fear and anxiety, than those who have seizures lateralized to limbic structures on the left side. However, there have been some inconsistent reports regarding the presence of these laterality effects. The use of animal models of epilepsy can help circumvent many of the methodological and ethical issues that arise from human clinical studies.

Chronic Jet Lag Simulation Decreases Hippocampal Neurogenesis and Enhances Depressive Behaviors and Cognitive Deficits in Adult Male Rats.

There is a long history that protracted periods of circadian disruption, such as through frequent transmeridian travel or rotating shift work, can have a significant impact on brain function and health. In addition, several studies have shown that chronic periods of circadian misalignment can be a significant risk factor for the development of depression and anxiety in some individuals with a history of psychiatric illness. In animal models, circadian disruption can be introduced through either phase advances or delays in the light-dark cycle.

Spatial exploration induced expression of immediate early genes Fos and Zif268 in adult-born neurons Is reduced after pentylenetetrazole kindling.

Seizure activity stimulates adult neurogenesis, the birth of new neurons, in the hippocampus. Many new neurons that develop in the presence of repeatedly induced seizures acquire abnormal morphological and functional characteristics that can promote network hyperexcitability and hippocampal dysfunction. However, the impact of seizure induced neurogenesis on behaviour remains poorly understood.

Increased task demand during spatial memory testing recruits the anterior cingulate cortex.

We examined whether increasing retrieval difficulty in a spatial memory task would promote the recruitment of the anterior cingulate cortex (ACC) similar to what is typically observed during remote memory retrieval. Rats were trained on the hidden platform version of the Morris Water Task and tested three or 30 d later. Retrieval difficulty was manipulated by removing several prominent extra-pool cues from the testing room.

Imipramine protects against the deleterious effects of chronic corticosterone on depression-like behavior, hippocampal reelin expression, and neuronal maturation.

We have hypothesized that a downregulation of reelin and deficient maturation of adult-born hippocampal neurons are important factors in the pathogenesis of depression. This hypothesis is based on previous work showing that depression-like behavior in rats treated with protracted corticosterone develops in concert with decreased dendritic complexity in newborn hippocampal granule neurons and decreased reelin expression in the proliferative subgranular zone of the dentate gyrus. In addition, heterozygous reeler mice with approximately 50% of normal brain levels of reelin are more vulnerable to the depressogenic effects of corticosterone than wild-type mice.

Vascular growth factors in neuropsychiatry.

Recent advances in understanding the cellular and molecular basis of psychiatric illnesses have shed light on the important role played by trophic factors in modulating functional parameters associated with disease causality and drug action. Disease mechanisms are now thought to involve multiple cell types, including neurons and endothelial cells. These functionally distinct but interactively coupled cell types engage in cellular cross talk via shared and common signaling molecules.

Illuminating hippocampal control of fear memory and anxiety.

Previous reports on dorsal and ventral hippocampal regulation of context learning versus anxiety have been mixed. In this issue of Neuron, a new study by Kheirbek et al. (2013) using optogenetics demonstrates that dentate gyrus granule cell activity in dorsal hippocampus encodes contextual fear learning while ventral granule cell activity regulates anxiety behavior.

Impaired recruitment of seizure-generated neurons into functional memory networks of the adult dentate gyrus following long-term amygdala kindling.

Epileptic seizures increase the birth of new neurons in the adult hippocampus. Although the consequences of aberrant neurogenesis on behavior are not fully understood, one hypothesis is that seizure-generated neurons might form faulty circuits that disrupt hippocampal functions, such as learning and memory. In the present study, we employed long-term amygdala kindling (i.

Neurodevelopmental anomalies of the hippocampus in rats exposed to weak intensity complex magnetic fields throughout gestation.

There has been increasing interest on the possible harmful effects of prenatal exposure to magnetic fields. To investigate the effect of weak intensity magnetic fields on the prenatal brain, pregnant Wistar rats were continuously exposed to one of four intensities (reference: 5-20 nT; low 30-50 nT; medium 90-580 nT; high 590-1200 nT) of a complex magnetic field sequence designed to interfere with brain development. As adults, rats exposed to the low-intensity (30-50 nT) complex magnetic field displayed impairments in contextual fear learning and showed anomalies in the cytological and morphological development of the hippocampus.

Neuritin produces antidepressant actions and blocks the neuronal and behavioral deficits caused by chronic stress.

Decreased neuronal dendrite branching and plasticity of the hippocampus, a limbic structure implicated in mood disorders, is thought to contribute to the symptoms of depression. However, the mechanisms underlying this effect, as well as the actions of antidepressant treatment, remain poorly characterized. Here, we show that hippocampal expression of neuritin, an activity-dependent gene that regulates neuronal plasticity, is decreased by chronic unpredictable stress (CUS) and that antidepressant treatment reverses this effect.

Vascular endothelial growth factor regulates adult hippocampal cell proliferation through MEK/ERK- and PI3K/Akt-dependent signaling.

Vascular endothelial growth factor (VEGF) is a hypoxia-induced angiogenic protein that exhibits a broad range of neurotrophic and neuroprotective effects in the central nervous system. Given that neurogenesis occurs in close proximity to blood vessels, increasing evidence has suggested that VEGF may constitute an important link between neurogenesis and angiogenesis. Although it is known that VEGF can directly stimulate the proliferation of neuronal progenitors, the underlying signaling pathways responsible in this process are not fully understood.

Antidepressant effects of fibroblast growth factor-2 in behavioral and cellular models of depression.

Background: Basic and clinical studies report that the expression of fibroblast growth factor-2 (FGF-2) is decreased in the prefrontal cortex (PFC) of depressed subjects or rodents exposed to stress and increased following antidepressant treatment. Here, we aim to determine if 1) FGF-2/fibroblast growth factor receptor (FGFR) signaling is sufficient and required for mediating an antidepressant response behaviorally and cellularly; and 2) if the antidepressant actions of FGF-2 are mediated specifically by the PFC.

Methods: The role of FGF-2 signaling in behavioral models of depression and anxiety was tested using chronic unpredictable stress (CUS)/sucrose consumption test (SCT), forced swim test (FST), and novelty suppressed feeding test (NSFT).

Role of vascular endothelial growth factor in adult hippocampal neurogenesis: implications for the pathophysiology and treatment of depression.

It is now well established that the adult brain has the capacity to generate new neurons throughout life. Although the functional significance of adult neurogenesis still remains to be established, increasing evidence has implicated compromised hippocampal neurogenesis as a possible contributor in the development of major depressive disorder. Antidepressants increase hippocampal neurogenesis and there is evidence in rodent models that the therapeutic efficacy of these agents is attributable, in part, to this neurogenic effect.

Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength.

Decreased levels of disrupted-in-schizophrenia 1 (DISC1) are associated with expansion of the dentate granule cell layer in normal and kindled rats.

Disrupted-in-schizophrenia 1 (DISC1) is a candidate gene involved in the pathogenesis of schizophrenia. DISC1 expression is particularly abundant in the adult dentate gyrus, in which decreased levels lead to aberrant growth, impaired migration, and accelerated integration of adult generated neurons. Because seizures can also result in similar changes, we tested the hypothesis that DISC1 expression may be altered in an animal model of epilepsy.

Altered synapsin I immunoreactivity and fear behavior in male and female rats subjected to long-term amygdala kindling.

Long-term amygdala kindling dramatically increases fearful behavior in both male and female rats. In this experiment, we studied the relation between sex, kindled fear behavior, and synapsin I immunoreactivity in various brain regions. Male and female adult Long-Evans rats received either 99 left amygdala kindling stimulations or sham stimulations.

Postnatal inflammation increases seizure susceptibility in adult rats.

There are critical postnatal periods during which even subtle interventions can have long-lasting effects on adult physiology. We asked whether an immune challenge during early postnatal development can alter neuronal excitability and seizure susceptibility in adults. Postnatal day 14 (P14) male Sprague Dawley rats were injected with the bacterial endotoxin lipopolysaccharide (LPS), and control animals received sterile saline.

Effect of different doses of corticosterone on depression-like behavior and HPA axis responses to a novel stressor.

Stress is recognized to precipitate depressive illness, yet the specific relationship between stress, glucocorticoids and depression is not well understood. We have recently shown that repeated corticosterone (CORT) injections reliably increase depression-like behavior on the forced-swim test in rats, suggesting that glucocorticoids can precipitate depressive symptomatology. The purpose of this experiment was to determine the extent to which the effects of CORT on depression-like behavior depend on (1) the dose-injected and (2) the duration of treatment.