Neuronal membrane components that bind alpha-bungarotoxin with high affinity have only recently been shown unambiguously to function as nicotinic receptors. Activation of the receptors increases intracellular levels of free calcium in... more
Neuronal membrane components that bind alpha-bungarotoxin with high affinity have only recently been shown unambiguously to function as nicotinic receptors. Activation of the receptors increases intracellular levels of free calcium in neurons. In the chick ciliary ganglion, where the receptors have been studied in some detail, they have been shown to have a predominantly nonsynaptic location on neurons and may be concentrated on pseudodendrites emerging from the somata. This has raised questions about the physiological significance of the receptors for the neurons. Here we show that activation of the receptors on isolated ciliary ganglion neurons in cell culture produces neurite retraction. Focal application of either nicotine or ACh at low concentrations induces the retraction, and alpha-bungarotoxin blocks the effect. The retraction requires external calcium and is confined to the individual neurite stimulated with agonist. Brief exposure to elevated concentrations of K+ also indu...
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Cell-specific expression of nicotinic acetylcholine receptors (AChRs) was examined using ciliary and choroid neurons isolated from chick ciliary ganglia. At embryonic days 13 and 14 (E13,14) the neurons can be distinguished by size, with... more
Cell-specific expression of nicotinic acetylcholine receptors (AChRs) was examined using ciliary and choroid neurons isolated from chick ciliary ganglia. At embryonic days 13 and 14 (E13,14) the neurons can be distinguished by size, with ciliary neuron soma diameters exceeding those of choroid neurons by about twofold. Both neuronal populations are known to express two major AChR types: alpha3*-AChRs recognized by mAb35, that contain alpha3, alpha5, beta4, and occasionally beta2 subunits, and alpha-bungarotoxin (alphaBgt)-AChRs recognized and blocked by alphaBgt, that contain alpha7 subunits. We found that maximal whole cell current densities (I/C(m)) mediated by alphaBgt-AChRs were threefold larger for choroid compared with ciliary neurons, while alpha3*-AChR current densities were similar in the two populations. Different densities of total cell-surface alphaBgt-AChRs could not explain the distinct alphaBgt-AChR response densities associated with ciliary and choroid neurons. Cilia...
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Neuronal acetylcholine receptors (AChRs) that bind α-bungarotoxin (αBgt) (αBgt-AChRs) have previously been found to contain at least one of the α7- α9 gene products. No other gene products of the 11 neuronal AChR genes cloned to date from... more
Neuronal acetylcholine receptors (AChRs) that bind α-bungarotoxin (αBgt) (αBgt-AChRs) have previously been found to contain at least one of the α7- α9 gene products. No other gene products of the 11 neuronal AChR genes cloned to date from rat and/or chick have been identified in such receptors. Chick ciliary ganglia have about 20 fmol of αBgt-AChRs that contain α7 subunits and 5 fmol of synaptic-type AChRs that bind the monoclonal antibody (mAb) 35 and collectively contain α3, β4, α5, and, to a lesser extent, β2 subunits. Using a sensitive solid-phase immunoprecipitation assay, we show here that ciliary ganglia have about 1 fmol of novel putative AChRs that bind both αBgt and mAb 35 but appear to lack all of the known neuronal AChR gene products in ciliary ganglia, including α3, α5, α7, β2, and β4. The putative receptors are also unlikely to contain either α8 or α9 gene products, because of the known expression patterns of these gene products. Nonetheless, the component sediments at...
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The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in... more
The early-life environment critically influences neurodevelopment and later psychological health. To elucidate neural and environmental elements that shape emotional behavior, we developed a rat model of individual differences in temperament and environmental reactivity. We selectively bred rats for high versus low behavioral response to novelty and found that high-reactive (bred high-responder, bHR) rats displayed greater risk-taking, impulsivity and aggression relative to low-reactive (bred low-responder, bLR) rats, which showed high levels of anxiety/depression-like behavior and certain stress vulnerability. The bHR/bLR traits are heritable, but prior work revealed bHR/bLR maternal style differences, with bLR dams showing more maternal attention than bHRs. The present study implemented a cross-fostering paradigm to examine the contribution of maternal behavior to the brain development and emotional behavior of bLR offspring. bLR offspring were reared by biological bLR mothers or fostered to a bLR or bHR mother and then evaluated to determine the effects on the following: (1) developmental gene expression in the hippocampus and amygdala and (2) adult anxiety/depression-like behavior. Genome-wide expression profiling showed that cross-fostering bLR rats to bHR mothers shifted developmental gene expression in the amygdala (but not hippocampus), reduced adult anxiety and enhanced social interaction. Our findings illustrate how an early-life manipulation such as cross-fostering changes the brain's developmental trajectory and ultimately impacts adult behavior. Moreover, while earlier studies highlighted hippocampal differences contributing to the bHR/bLR phenotypes, our results point to a role of the amygdala as well. Future work will pursue genetic and cellular mechanisms within the amygdala that contribute to bHR/bLR behavior either at baseline or following environmental manipulations. © 2015 S. Karger AG, Basel.
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Neuronal membrane components that bind a-bungarotoxin with high affinity have only recently been shown unambig- uously to function as nicotinic receptors. Activation of the receptors increases intracellular levels of free calcium in... more
Neuronal membrane components that bind a-bungarotoxin with high affinity have only recently been shown unambig- uously to function as nicotinic receptors. Activation of the receptors increases intracellular levels of free calcium in neurons. In the chick ciliary ganglion, where the receptors have been studied in some detail, they have been shown to have a predominantly nonsynaptic location on neurons and
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Research Interests: Cognitive Science, Biophysics, Drug interactions, Enzyme Inhibitors, Patch-clamp and imaging techniques, and 16 moreSignal Transduction, Nicotine, Nitric oxide, Animals, Nicotinic Acetylcholine Receptors, Acetylcholine, Neurons, Analysis of Variance, Time Factors, SYNAPSES, Cellular and Molecular Neuroscience, Neurosciences, Potassium Chloride, Patch Clamp, Cholinergic agents, and Phospholipase C
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Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children's developing brain and... more
Selective serotonin reuptake inhibitor (SSRI) antidepressants are the mainstay treatment for the 10-20% of pregnant and postpartum women who suffer major depression, but the effects of SSRIs on their children's developing brain and later emotional health are poorly understood. SSRI use during pregnancy can elicit antidepressant withdrawal in newborns and increase toddlers' anxiety and social avoidance. In rodents, perinatal SSRI exposure increases adult depression- and anxiety-like behavior, although certain individuals are more vulnerable to these effects than others. Our study establishes a rodent model of individual differences in susceptibility to perinatal SSRI exposure, utilizing selectively bred Low Responder (bLR) and High Responder (bHR) rats that were previously bred for high versus low behavioral response to novelty. Pregnant bHR/bLR females were chronically treated with the SSRI paroxetine (10mg/kg/day p.o.) to examine its effects on offspring's emotional beh...