Expression and Distribution of Neuropeptide-Expressing Cells Throughout the Rodent Paraventricular Nucleus of the Thalamus

The paraventricular nucleus of the thalamus (PVT) has been shown to make significant contributions to affective and motivated behavior, but a comprehensive description of the neurochemicals expressed in the cells of this brain region has never been presented. While the PVT is believed to be composed of projection neurons that primarily use as their neurotransmitter the excitatory amino acid, glutamate, several neuropeptides have also been described in this brain region. In this review article, we combine published literature with our observations from the Allen Brain Atlas to describe in detail the expression and distribution of neuropeptides in cells throughout the mouse and rat PVT, with a special focus on neuropeptides known to be involved in behavior. Several themes emerge from this investigation. First, while the majority of neuropeptides are expressed across the antero-posterior axis of the PVT, they generally exist in a gradient, in which expression is most dense but not exclusive in either the anterior or posterior PVT, although other neuropeptides display somewhat more equal expression in the anterior and posterior PVT but have reduced expression in the middle PVT. Second, we find overall that neuropeptides involved in arousal are more highly expressed in the anterior PVT, those involved in depression-like behavior are more highly expressed in the posterior PVT, and those involved in reward are more highly expressed in the medial PVT, while those involved in the intake of food and drugs of abuse are distributed throughout the PVT. Third, the pattern and content of neuropeptide expression in mice and rats appear not to be identical, and many neuropeptides found in the mouse PVT have not yet been demonstrated in the rat. Thus, while significantly more work is required to uncover the expression patterns and specific roles of individual neuropeptides in the PVT, the evidence thus far supports the existence of a diverse yet highly organized system of neuropeptides in this nucleus. Determined in part by their location within the PVT and their network of projections, the function of the neuropeptides in this system likely involves intricate coordination to influence both affective and motivated behavior.

How ribbons make ‘sense’ for vision

The processing of light by the retina and brain provides the basis for visual perception. Photons are captured and converted to electrical signals by rod and cone photoreceptor cells in the retina. These electrical signals are converted to chemical signals for transmission to downstream neurons. This article provides an overview of the mechanisms involved in transmitting light responses from rods and cones. Chemical signalling occurs at synapses between neurons. In keeping with many other neurons, the chemical messenger released by photoreceptors is the amino acid glutamate, which is packaged into small spherical vesicles. Each photoreceptor synaptic terminal has thousands of synaptic vesicles. Some of these vesicles are attached to the face of planar structures known as ribbons. Ribbons capture and deliver vesicles to release sites at the bottom of the ribbon. Upon stimulation, vesicles fuse with the cell membrane and release their contents. Glutamate molecules diffuse through the extracellular space to reach specialized receptors that regulate the activity of downstream neurons. We discuss how rates of vesicle attachment to ribbons, delivery of vesicles down the ribbon and the release of glutamate shape the information provided to downstream neurons in the visual system.

Tracking Polymicrobial Metabolism in Cystic Fibrosis Airways: Pseudomonas aeruginosa Metabolism and Physiology Are Influenced by Rothia mucilaginosa -Derived Metabolites

ABSTRACT Due to a lack of effective immune clearance, the airways of cystic fibrosis patients are colonized by polymicrobial communities. One of the most widespread and destructive opportunistic pathogens is Pseudomonas aeruginosa ; however, P. aeruginosa does not colonize the airways alone. Microbes that are common in the oral cavity, such as Rothia mucilaginosa , are also present in cystic fibrosis patient sputum and have metabolic capacities different from those of P. aeruginosa . Here we examine the metabolic interactions of P. aeruginosa and R. mucilaginosa using stable-isotope-assisted metabolomics. Glucose-derived 13 C was incorporated into glycolysis metabolites, namely, lactate and acetate, and some amino acids in R. mucilaginosa grown aerobically and anaerobically. The amino acid glutamate was unlabeled in the R. mucilaginosa supernatant but incorporated the 13 C label after P. aeruginosa was cross-fed the R. mucilaginosa supernatant in minimal medium and artificial-sputum medium. We provide evidence that P. aeruginosa utilizes R. mucilaginosa -produced metabolites as precursors for generation of primary metabolites, including glutamate. IMPORTANCE Pseudomonas aeruginosa is a dominant and persistent cystic fibrosis pathogen. Although P. aeruginosa is accompanied by other microbes in the airways of cystic fibrosis patients, few cystic fibrosis studies show how P. aeruginosa is affected by the metabolism of other bacteria. Here, we demonstrate that P. aeruginosa generates primary metabolites using substrates produced by another microbe that is prevalent in the airways of cystic fibrosis patients, Rothia mucilaginosa . These results indicate that P. aeruginosa may get a metabolic boost from its microbial neighbor, which might contribute to its pathogenesis in the airways of cystic fibrosis patients.

Monosodium Glutamate in the Diet Does Not Raise Brain Glutamate Concentrations or Disrupt Brain Functions

The non-essential amino acid glutamate participates in numerous metabolic pathways in the body. It also performs important physiologic functions, which include a sensory role as one of the basic tastes (as monosodium glutamate [MSG]), and a role in neuronal function as the dominant excitatory neurotransmitter in the central nervous system. Its pleasant taste (as MSG) has led to its inclusion as a flavoring agent in foods for centuries. Glutamate’s neurotransmitter role was discovered only in the last 60 years. Its inclusion in foods has necessitated its safety evaluation, which has raised concerns about its transfer into the blood ultimately increasing brain glutamate levels, thereby causing functional disruptions because it is a neurotransmitter. This concern, originally raised almost 50 years ago, has led to an extensive series of scientific studies to examine this issue, conducted primarily in rodents, non-human primates, and humans. The key findings have been that (a) the ingestion of MSG in the diet does not produce appreciable increases in glutamate concentrations in blood, except when given experimentally in amounts vastly in excess of normal intake levels; and (b) the blood-brain barrier effectively restricts the passage of glutamate from the blood into the brain, such that brain glutamate levels only rise when blood glutamate concentrations are raised experimentally via non-physiologic means. These and related discoveries explain why the ingestion of MSG in the diet does not lead to an increase in brain glutamate concentrations, and thus does not produce functional disruptions in brain. This article briefly summarizes key experimental findings that evaluate whether MSG in the diet poses a threat to brain function.

Neuroprotection by glucagon: role of gluconeogenesis

Object The severity of neurological impairment following traumatic brain injury (TBI) is exacerbated by several endogenous processes, including hyperglycemia, hypotension, and the generation of glutamate. However, in addition to controlling hyperglycemia, insulin has pleiotropic effects on tissue metabolism, which include reducing the concentration of the neurotoxic amino acid glutamate, making it unclear whether insulin's beneficial effects are attributable to the establishment of euglycemia per se. In the present study, the authors asked if reducing glutamate via approaches that do not lower glucose levels would improve neurological outcome following TBI. Methods Glucagon activates gluconeogenesis by increasing the hepatic uptake of amino acids such as glutamate and facilitating their conversion to glucose. Glucagon was administered as a single intraperitoneal injection before or after closed head injury (CHI). Neurological function, brain histological features, blood glutamate and glucose levels, and CSF glutamate concentrations were measured. Results A single intraperitoneal injection of glucagon (25 μg) into mice 10 minutes before or after CHI reduced lesion size by about 60% (p < 0.0001) and accelerated neurological recovery. The neuroprotective effect of glucagon was related to gluconeogenesis by decreasing the concentration of the neuroexcitatory amino acid glutamate in the circulation from 207 ± 32.1 μmol/L in untreated mice to 101.11 ± 21.6 μmol/L in treated mice (p < 0.001); a similar effect occurred in the CSF. The neuroprotective effect of glucagon was seen notwithstanding the attendant increase in blood glucose, the final substrate of gluconeogenesis. Conclusions Glucagon exerts a marked neuroprotective effect post-TBI by decreasing CNS glutamate. Glucagon was beneficial despite increasing blood glucose. Favorable effects also occurred when glucagon was given prior to TBI, suggesting its involvement in the preconditioning process. Thus, glucagon may be of value in providing neuroprotection when administered after TBI or prior to certain neurosurgical or cardiac interventions in which the incidence of perioperative ischemia is high.

Sol-Gel Optical Sensors for Glutamate

The amino acid glutamate is the major excitatory neurotransmitter used in the nervous system for interneuronal communication. It is used throughout the brain by various neuronal pathways including those involved in learning and memory, locomotion, and sensory perception. Because glutamate is released from neurons on a millisecond time scale into sub-micrometer spaces, the development of a glutamate biosensor with high temporal and spatial resolution is of great interest for the study of neurological function and disease. Here, we demonstrate the feasibility of an optical glutamate sensor based on the sol-gel encapsulation of the enzyme glutamate dehydrogenase (GDH). GDH catalyses the oxidative deamination of glutamate and the reduction of NAD+ to NADH. NADH fluorescence is the basis of the sensor detection. Thermodynamic and kinetic studies show that GDH remains active in the sol-gel matrix and that the reaction rate is correlated to the glutamate concentration.