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N,N-Diethyl- meta-toluamide (DEET) is the most widely used insect repellent, but it requires repeated application at high, potentially harmful, concentrations, which is prohibitively impractical and costly in the countries suffering [...]

Many important physiological, behavioral, and psychoemotional effects of intravenous (IV) cocaine (COC) are too fast and transient compared with pharmacokinetic predictions, suggesting a possible involvement of peripheral neural mechanisms in their triggering. In the present study, we examined changes in cortical electroencephalogram (EEG) and neck electromyogram (EMG) induced in freely moving rats by IV COC administration at low, reinforcing doses (0.25-1.0 mg/kg) and compared them with those induced by an auditory stimulus and IV COC methiodide, which cannot cross the blood-brain barrier. We found that COC induces rapid, strong, and prolonged EEG desynchronization, associated with decrease in alpha and increase in beta and gamma activities, and EMG activation and that both begin within 2-6 s following the start of a 10-s injection; immediate components of this effect were dose independent. The rapid COC-induced changes in EEG and EMG resembled those induced by an auditory stimulus; the latter effects had shorter onset latencies and durations and were fully blocked during urethane anesthesia. Although urethane anesthesia completely blocked COC-induced EMG activation and rapid components of EEG response, COC still induced EEG desynchronization that was much weaker, greatly delayed (~60 s), and associated with tonic decreases in delta and increases in alpha, beta, and gamma activities. Surprisingly, IV saline delivered during slow-wave sleep (but not quite wakefulness) also induced a transient EEG desynchronization but without changes in EMG activity; these effects were also fully blocked during anesthesia. Peripherally acting COC methiodide fully mimicked rapid EEG and EMG effects of regular COC, but the effects at an equimolar dose were less prolonged than those with regular COC. These data suggest that in awake animals IV COC, like somato-sensory stimuli, induces cortical activation and a subsequent motor response via its action on peripheral neural elements and involving rapid neural transmission. By providing a rapid neural si[G.sub.Na]l and triggering transient neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior. electroencephalography; electromyography; arousal; sensory effects; ionic channels; reinforcement doi: 10.1152/ajpregu.00628.2009

Genetic variation in neuregulin 1 (NRG1) is associated with schizophrenia. The disease-associated SNPs are noncoding, and their functional implications remain unknown. We hypothesized that differential expression of the NRG1 gene explains its association to the disease. We examined four of the disease-associated SNPs that make up the original risk haplotype in the 5' upstream region of the gene for their effects on mRNA abundance of NRG1 types I-IV in human postmortem hippocampus. Diagnostic comparisons revealed a 34% increase in type I mRNA in schizophrenia and an interaction of diagnosis and genotype (SNP8NRG221132) on this transcript. Of potentially greater interest, a single SNP within the risk haplotype (SNP8NRG243177) and a 22-kb block of this core haplotype are associated with mRNA expression for the novel type IV isoform in patients and controls. Bioinformatic promoter analyses indicate that both SNPs lead to a gain/loss of putative binding sites for three transcription factors, serum response factor, myelin transcription factor-1, and High Mobility Group Box Protein-1. These data implicate variation in isoform expression as a molecular mechanism for the genetic association of NRG1 with schizophrenia. genetics | mRNA | human postmortem brain | hippocampus | ErbB

Over the last decade, a large body of information regarding the amino acid sequences and tertiary structures of many proteins has accumulated. Subtle similarities in sequence patterns identified between glutamate receptors and bacterial periplasmic substrate-binding proteins have suggested that structural kinship exists between these protein families. Many of the bacterial periplasmic binding proteins but none of the glutamate receptors have been crystallized so far. The following article reviews how the resemblance between these two protein families led to computer-assisted structural models of crucial elements involved in ligand binding by various glutamate receptors. A plausible dynamic model of the molecular mechanism of activation and desensitization of glutamate-receptor channels is also discussed.

Two isoforms of the substance P (SP) receptor, differing in the length of the cytoplasmic carboxyl-terminus by [approximately equal to 8 kDa, have been detected previously in rat salivary glands and other tissues. The binding and functional properties of these two isoforms have been investigated using full-length (407 amino acids) and carboxyl-terminally truncated (324 amino acids) rat SP receptors transfected stably into Chinese hamster ovary cells. Both the full-length and the truncated receptor bound radiolabeled SP with a similar K.sub.d ([approximate equal to] 0.1 nM). The average number of high affinity SP binding sites per cell was 1.0 x [10.sup.5] and 0.3 x [10.sup.5] for the full-length and the truncated SP receptor, respectively. In both cell lines, SP induced a rapid but transient increase in cytosolic calcium concentration ([[Ca.sup.2+].sub.i]), which consisted of the release of [Ca.sup.2+] from intracellular stores and the influx of extracellular [Ca.sup.2+]. Both components are dependent on phospholipase C activation. Although the full-length and the truncated receptor utilize the same calcium pathways, they differ in their [EC.sub.50] values (0.28 nM for the full-length; 0.07 nM for the truncated). These differences in responsiveness may be related to the observed differences in receptor desensitization. The truncated receptor, in contrast to the full-length receptor, does not undergo rapid and long-lasting desensitization. Cells possessing the short isoform of the SP receptor would thus be expected to exhibit a prolonged responsiveness.

The importance of nonconserved residues on the central b-strand bundle region for the interaction of neutrophin-3 (NT-3) with nerve growth factor-based receptor (NGF) trkC as well as the different mechanisms that determine specificity in NT-3/trkC and GF/trkA ligand/receptor pairing were analyzed by using NGF variants that bind to trkC obtained through mutagenesis and recombinant dna manipulation. It was found that tkrC uses two sites to discriminate between the various neutrotrophins.

The class A scavenger receptors (SR) result in the adhesion of rodent microglia and human monocytes to surfaces coated with beta-amyloid fibrils. This causes the excretion of reactive oxygen species of neurotoxins and cell immobilization. Beta-amyloid fibrils stimulate the production of neurotoxins such as reactive oxygen species by microglia. The expression of SR by mononuclear phagocytes such as microglia causes endocytosis of oxidized low-density lipoproteins and cell-adhesion to extracellular matrix proteins modified by glucose.

Glial cell line-derived neurotrophic factor (GDNF)R-alpha, a glycosylphosphatidylinositol-linked GDNF receptor, binds GDNF and mediates Ret protein tyrosine kinase activation. Neuro-2a cells expressing GDNFR-alpha increase autophosphorylation of Ret on treatment with GDNF. Treatment with a combination of a soluble form of the receptor and GDNF in cells without GDNFR-alpha produces Ret protein activation. GDNF activates Ret protein in cultured embryonic rat spinal cord motor neurons.

[alpha]-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors that lack the glutamate receptor GluR2 subunit are [Ca.sup.2+]-permeable and exhibit inwardly rectifying current responses to kainate and AMPA. A proportion of cultured rat hippocampal neurons show similar [Ca.sup.2+]-permeable inwardly rectifying AMPA receptor currents. Inward rectification in these neurons was lost with intracellular dialysis and was not present in excised outside-out patches but was maintained in perforated-patch whole-cell recordings, suggesting that a diffusible cytoplasmic factor may be responsible for rectification. Inclusion of the naturally occurring polyamines spermine and spermidine in the recording pipette prevented loss of rectification in both whole-cell and excised-patch recordings; [Mg.sup.2+] and putrescine were without effect. Inward rectification of [Ca.sup.2+]-permeable AMPA receptors may reflect voltage-dependent channel block by intracellular polyamines.

The mutagenesis of the channel domain M2 is used in the investigation of the relative permeability of sodium, potassium and calcium of chicken alpha 7 neuronal nicotinic receptor. The calcium permeability is reduced by the mutations in the intermediate ring of the negatively charged residues found at the cytoplasmic end of M2 or site 1. Multiple effects are caused by the mutations of the two adjacent rings of leucins. The calcium transport is affected by the relative permeability of sodium and potassium and by the mutations at the two topographically distinct sites inside M2.

The evaluation of the levels and the reactivity of receptors of atrial natriuretic peptide (ANP), a circulating hormone in the blood, characterized by its vasorelaxant, natriuretic and diuretic activities and its property to suppress aldosterone secretion, is done by studies of the neuronal and astrocyte glial cultures derived from spontaneously hypertensive (SH) and normotensive (WKY) rat brain. C-type natriuretic peptide (CNP-22) is the most influential activator of guanosine 3',5-cyclic monophosphate (cGMP) levels in interneuronal cultures from the strains of SH and WKY rats, demonstrating the presence of ANP-B receptors. The presence of ANP-A receptors in SH and WKY rat astrocyte glial cultures is detected by the effective stimulatory activity of ANP on cGMP levels.

Immunohistochemical analyses using double and triple immunofluorescence staining were conducted on the olfactory bulb, basal forebrain, basal ganglia, brainstem and cerebellum to determine the possible colocalization of the alpha, beta and gamma subunits of gamma-aminobutyric acid (GABA) receptors. The results showed that GABA receptors in these tissues could be distinguished by five distinct combinations of subunits. Each combination corresponds to a receptor subtype, which can be used to characterize different populations of neurons.

The existence of subtypes of the neurotensin receptor in brain and peripheral tissues is studied. Recent studies involving the neurotensin receptor antagonist SR48692 have indicated the existence of subtypes of the neurotensin receptor. It has been found that SR48692 inhibits the binding of neurotensin to the cloned neurotensin receptor, and antagonizes neurotensin responses mediated through this receptor.

Claims made in the target article that information-that-specifies is contained in relations among structured energy arrays, considered as wholes, may well be true, but claims that information-that-specifies is only contained in irreducible relations among structured energy arrays, considered as wholes, fail to persuade, at least in the case of the blind.

The first electrophysiological studies on umami taste were conducted with rats and cats. Unlike humans, these animals did not show a large synergism between monosodium glutamate (MSG) and disodium guanylate (GMP) or disodium inosinate (IMP). The taste nerve responses of these animals to umami substances were not differentiated from the salt responses. The canine taste system was sensitive to umami substances and showed a large synergism between MSG and GMP or IMP. The umami substances showed no enhancing effects on other basic tastes. Amiloride, an inhibitor for the response to NaCl, did not inhibit the large response induced by the synergism between MSG and the nucleotides, indicating that the response to the umami substances is independent of the response to salt. Single-fiber analysis on the responses of mouse glossopharyngeal nerve and monkey primary taste cortex neurons also showed that the responses to umami substances are independent of other basic tastes. On the basis of these results, it was proposed that the umami taste is a fifth basic taste, and that there is a unique receptor for umami substances. Hence, we compared the taste of agonists for brain glutamate receptors. In humans, the order of intensity of umami taste induced by a mixture of 0.5 mmol/L GMP and 1.5 mmol/L of various agonists was glutamate [is greater than] ibotenate [is greater than] L(+)-2-amino-4-phosphonobutyric acid (L-AP4) = ([+ or -])1-aminocyclopentane-trans-1,3-dicarboxylic acid (ACPD). Kainate, N-methyl-D-aspartic acid (NMDA) and (RS)--amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), which are agonists for ionotropic receptors, had no umami taste. It was concluded that the umami receptor is not identical to any known glutamate receptors; there seems, therefore, to be a unique receptor for umami. J. Nutr. 130: 931S-934S, 2000. KEY WORDS: * dogs * synergism * taste nerve response * glutamate agonists * amino acids

Neural receptive fields are plastic: with experience, neurons in many brain regions change their spiking responses to relevant stimuli. Analysis of receptive field plasticity from experimental measurements is crucial for understanding how neural systems adapt their representations of relevant biological information. Current analysis methods using histogram estimates of spike rate functions in non-overlapping temporal windows do not track the evolution of receptive field plasticity on a fine time scale. Adaptive signal processing is an established engineering paradigm for estimating time-varying system parameters from experimental measurements. We present an adaptive filter algorithm for tracking neural receptive field plasticity based on point process models of spike train activity. We derive an instantaneous steepest descent algorithm by using as the criterion function the instantaneous log likelihood of a point process spike train model. We apply the point process adaptive filter algorithm in a study of spatial (place) receptive field properties of simulated and actual spike train data from rat CA1 hippocampal neurons. A stability analysis of the algorithm is sketched in the Appendix. The adaptive algorithm can update the place field parameter estimates on a millisecond time scale. It reliably tracked the migration, changes in scale, and changes in maximum firing rate characteristic of hippocampal place fields in a rat running on a linear track. Point process adaptive filtering offers an analytic method for studying the dynamics of neural receptive fields.

The interaction between odorants and olfactory receptors was examined using an olfactory receptor library expression. A total of 80 chimeric receptors from this library were evaluated against 26 odorants after being transfected into HEK-293 cells. The analysis identified three receptors that responded to micromolecular concentrations of carvone, (-)citronellal and limonene. The study also revealed that the mouse 17 receptor favors heptanal instead ofoctanal due to a single valine-to-isoleucine substitution.