Glial cell dysfunction and excessive glutamate receptor activation in spinal dorsal horn neurons are hallmark mechanisms of pathological pain. The way in which glial cell dysfunction leads to excessive glutamate receptor activation in the spinal sensory synapses remains unknown. We and others recently reported the downregulation of glial glutamate transporter (GT) protein expression in the spin...

Background : New antidepressant strategies are needed, due to unsatisfactory clinical efficacy and many side effects of commonly used drugs. Recent studies linking the pathophysiology depression with glutamatergic imbalance. There is hyperactivity main excitatory system (glutamatergic) its inhibition (GABAergic). N-methyl D-aspartate (NMDA) receptors as a part synapses potential targets for int...

The rostral ventrolateral medulla (RVLM) is an important site of cardiovascular control related to the tonic excitation and regulating the sympathetic vasomotor tone through local presympathetic neurons. Nitric oxide (NO) has been implicated in the modulation of neurotransmission by several areas of the central nervous system including the RVLM. However the pathways driving NO affects and the c...

BACKGROUND Caffeine stimulates calcium-induced calcium release (CICR) in many cell types. In neurons, caffeine stimulates CICR presynaptically and thus modulates neurotransmitter release. METHODOLOGY/PRINCIPAL FINDINGS Using the whole-cell patch-clamp technique we found that caffeine (20 mM) reversibly increased the frequency and decreased the amplitude of miniature excitatory postsynaptic cu...

Hypoxic/ischemic (HI) brain injury in newborn full-term and premature infants is a common and pervasive source of life time disabilities in cognitive and locomotor function. In the adult, HI induces glutamate release and excitotoxic cell death dependent on NMDA receptor activation. In animal models of the premature human infant, glutamate is also released following HI, but neurons are largely i...

Changes in synaptic strength mediated by ionotropic glutamate N-methyl-D-asparate (NMDA) receptors is generally considered to be the molecular mechanism underlying memory and learning. NMDA receptors themselves are subject to regulation through signaling pathways that are activated by G-protein-coupled receptors (GPCRs). In this study we investigate the ability of NMDA receptors to regulate the...

Glutamate receptors, especially N-methyl-d-aspartate (NMDA) receptors, are hypothesized to play key roles in opiate tolerance and withdrawal. There is also accumulating evidence that alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonists and group II metabotropic glutamate receptor (mGluR) agonists attenuate opiate withdrawal. However, most existing data are derive...

NMDA-type glutamate receptors play a critical role in neuronal synaptogenesis, plasticity, and excitotoxic death. Recent studies indicate that functional NMDA receptors are also expressed in certain glial populations in the normal brain. Using immunohistochemical methods, we detected the presence of the NMDA receptor 2B (NR2B) subunit of the NMDA receptor in neurons but not astrocytes in the CA...

Nociceptive primary afferents release glutamate, activating postsynaptic glutamate receptors on spinal cord dorsal horn neurons. Glutamate receptors, both ionotropic and metabotropic, are also expressed on presynaptic terminals, where they regulate neurotransmitter release. During the last two decades, a wide number of studies have characterized the properties of presynaptic glutamatergic recep...