Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory.

The impact of tonic GABAA receptor-mediated inhibition on neuronal excitability varies across brain region and cell type.

The diversity of GABAA receptor (GABAAR) subunits and the numerous configurations during subunit assembly give rise to a variety of receptors with different functional properties. This heterogeneity results in variations in GABAergic conductances across numerous brain regions and cell types. Phasic inhibition is mediated by synaptically-localized receptors with a low affinity for GABA and results in a transient, rapidly desensitizing GABAergic conductance; whereas, tonic inhibition is mediated by extrasynaptic receptors with a high affinity for GABA and results in a persistent GABAergic conductance.

Loss of Gabrd in CRH neurons blunts the corticosterone response to stress and diminishes stress-related behaviors.

The hypothalamic-pituitary-adrenal (HPA) axis is under tight regulation by strong GABAergic inhibition onto corticotropin-releasing hormone (CRH) neurons in the paraventricular nucleus (PVN) of the hypothalamus. CRH neurons receive two forms of GABAergic inhibition, phasic and tonic, but the specific roles of these two types of signaling have not yet been studied in this cell type. Our lab recently demonstrated a role for the GABAAR δ subunit in the tonic GABAergic regulation of CRH neurons.

Impact of inhibitory constraint of interneurons on neuronal excitability.

Tonic inhibition is thought to dampen the excitability of principal neurons; however, little is known about the role of tonic GABAergic inhibition in interneurons and the impact on principal neuron excitability. In many brain regions, tonic GABAergic inhibition is mediated by extrasynaptic, δ-subunit-containing GABAA receptors (GABAARs). In the present study we demonstrate the importance of GABAAR δ-subunit-mediated tonic inhibition in interneurons.

Alterations in brain metabolism during the first year of HIV infection.

Migration of both uninfected and infected monocytes into the brain during acute HIV infection likely initiates metabolic changes that can be observed with magnetic resonance spectroscopy (MRS). Herein, we measured changes in brain metabolism during the first year of HIV infection and examined the relationship of these metabolite levels to CD16+ monocyte populations measured in the blood. MRS was performed on nine HIV+ subjects identified during acute HIV infection and nine seronegative control subjects.

Factor analysis of proton MR spectroscopic imaging data in HIV infection: metabolite-derived factors help identify infection and dementia.

Purpose: To develop a relevant pathophysiologic model of human immunodeficiency virus (HIV)-associated dementia by studying regional variations in metabolite levels measured with magnetic resonance (MR) spectroscopic imaging and their relationship to immunologic measures and cognitive dysfunction.

Materials And Methods: This was a HIPAA-compliant, institutional review board-approved study involving written informed consent. Distributions of N-acetylaspartate (NAA), choline (Cho), and creatine (Cr) concentrations in 94 subjects (20 seronegative controls and 74 HIV-positive subjects; 34 of the HIV-positive subjects having HIV-associated dementia; 63 men, 31 women; mean age, 40 years) were determined with proton (hydrogen 1 [(1)H]) MR spectroscopic imaging.

In vivo proton magnetic resonance spectroscopy reveals region specific metabolic responses to SIV infection in the macaque brain.

Background: In vivo proton magnetic resonance spectroscopy (1H-MRS) studies of HIV-infected humans have demonstrated significant metabolic abnormalities that vary by brain region, but the causes are poorly understood. Metabolic changes in the frontal cortex, basal ganglia and white matter in 18 SIV-infected macaques were investigated using MRS during the first month of infection.

Results: Changes in the N-acetylaspartate (NAA), choline (Cho), myo-inositol (MI), creatine (Cr) and glutamine/glutamate (Glx) resonances were quantified both in absolute terms and relative to the creatine resonance.

Factor analysis reveals differences in brain metabolism in macaques with SIV/AIDS and those with SIV-induced encephalitis.

MRS has often been used to study metabolic processes in the HIV-infected brain. However, it remains unclear how changes in individual metabolites are related to one another in this context of virus-induced central nervous system dysfunction. We used factor analysis (FA) to identify patterns of metabolite distributions from an MRS study of healthy macaques and those infected with simian immunodeficiency virus (SIV) which were moribund with AIDS.

Metabolic markers of neuronal injury correlate with SIV CNS disease severity and inoculum in the macaque model of neuroAIDS.

In vivo MR spectroscopy (MRS) studies have shown reductions in NAA/Cr levels in patients with severe neurocognitive deficits due to AIDS dementia complex (ADC), also known as neuroAIDS. The relationship between the cellular changes within the brain during neuroAIDS and the role of NAA/Cr as a metabolic marker remains unclear. In order to clarify the relationship between NAA/Cr and disease severity we utilized the simian immunodeficiency virus (SIV)/macaque model of encephalitis.

Magnetic resonance spectroscopy study of oxygen therapy in ischemic stroke.

Background And Purpose: Recent studies suggest that normobaric oxygen therapy (NBO) is neuroprotective in acute ischemic stroke.

Methods: We performed multivoxel magnetic resonance spectroscopic imaging and diffusion/perfusion MRI in patients with stroke treated with NBO or room air. Imaging was performed before, during, and after therapy.

Effects of acute and chronic ethanol exposure on the behavior of adult zebrafish (Danio rerio).

The zebrafish has been a popular subject of embryology and genetic research for the past three decades. Recently, however, the interest in its neurobiology and behavior has also increased. Nevertheless, compared to other model organisms, e.