Physiological evidence that <scp>d</scp>-aspartate activates a current distinct from ionotropic glutamate receptor currents in <i>Aplysia californica</i> neurons

Carlson, Stephen L.; Fieber, Lynne A.

doi:10.1152/jn.00403.2011

Cited by 10 publications

(22 citation statements)

References 45 publications

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“…In our prior studies, 25% of buccal S cluster neurons and 48% of pleural ventrocaudal neurons had D-Asp-elicited whole-cell currents but lacked L-glutamate (L-Glu) induced responses (Fieber et al 2010; Carlson and Fieber 2011). Additionally, D-Asp activated currents independently of the L-GluR agonists AMPA and NMDA (Carlson and Fieber 2012).…”

Section: Introductionmentioning

confidence: 95%

Pharmacological evidence that D‐aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica

2012

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D-Aspartate (D-Asp) activates a nonspecific cation current of unknown identity independent of L-glutamate (L-Glu) in neurons of Aplysia californica. Whole-cell voltage clamp studies were conducted using primary cultures of Aplysia buccal S cluster (BSC) neurons to characterize these receptor channels pharmacologically. The N-methyl-D-aspartate receptor (NMDAR) coagonist glycine potentiated D-Asp currents only at −30 mV, while D-serine did not potentiate D-Asp currents at any amplitude. Portions of D-Asp currents were blocked by the L-Glu antagonists kynurenate, DL-2-amino-5-phosphonopentanoic acid (APV), (2S,3R)-1-(phenanthren-2-carbonyl)piperazine-2,3-dicarboxylic acid (PPDA), and 1,3-dihydro-5-[3-[4-(phenylmethyl)-1–2H-benzimidazol-2-one (TCS46b), suggesting that L-Glu channels, particularly NMDAR-like channels, may partially contribute to D-Asp whole-cell currents. In contrast, L-Glu currents were unaffected by APV, and showed greater block by kynurenate, suggesting that D-Asp and L-Glu act, in part, at different sites. The excitatory amino acid transport blocker DL-threo-b-Benzyloxyaspartic acid (TBOA) blocked a fraction of D-Asp currents, suggesting that currents associated with these transporters also contribute. Non-NMDA L-GluR antagonists that preferentially block alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionic acid (AMPA)/kainate receptors significantly increased D-Asp currents, suggesting a possible allosteric potentiating effect of these antagonists on D-Asp receptors. L-Glu-induced currents were significantly reduced in the presence of bath-applied D-Asp, whereas bath-applied L-Glu had no effect on D-Asp-induced currents. The mixed effects of these agents on D-Asp-induced currents in Aplysia illustrate that the underlying channels are not uniformly characteristic of any known agonist associated channel type.

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Section: Introductionmentioning

confidence: 95%

Pharmacological evidence that D‐aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica

2012

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“…Applied L-Glu activated excitatory currents in PVC and BSC sensory neurons (Carlson and Fieber, 2011, 2012). D-Aspartate (D-Asp) is a relevant doppelganger of L-Glu (Olverman et al, 1988) whose physiological actions have recently been studied (Errico et al, 2008, 2011).…”

Section: Introductionmentioning

confidence: 99%

Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica

Kempsell¹,

Fieber²

2014

Front. Aging Neurosci.

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Invertebrate models have advantages for understanding the basis of behavioral aging due to their simple nervous systems and short lifespans. The potential usefulness of Aplysia californica in aging research is apparent from its long history of neurobiological research, but it has been underexploited in this model use. Aging of simple reflexes at both single sensory neuron and neural circuit levels was studied to connect behavioral aging to neurophysiological aging. The tail withdrawal reflex (TWR), righting reflex, and biting response were measured throughout sexual maturity in 3 cohorts of hatchery-reared animals of known age. Reflex times increased and reflex amplitudes decreased significantly during aging. Aging in sensory neurons of animals with deficits in measures of the TWR and biting response resulted in significantly reduced excitability in old animals compared to their younger siblings. The threshold for firing increased while the number of action potentials in response to depolarizing current injection decreased during aging in sensory neurons, but not in tail motoneurons. Glutamate receptor-activated responses in sensory neurons also decreased with aging. In old tail motoneurons, the amplitude of evoked EPSPs following tail shock decreased, presumably due to reduced sensory neuron excitability during aging. The results were used to develop stages of aging relevant to both hatchery-reared and wild-caught Aplysia. Aplysia is a viable aging model in which the contributions of differential aging of components of neural circuits may be assessed.

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“…Pedal ganglion had the highest iGluR expression, with the glutamatergic nature of pedal motoneuron transmission corroborated by physiological studies [72, 73]. Variations in the frequency and amplitude of ionic currents activated by the iGluR agonists L-Glu and D-Asp have been documented in neurons isolated from different ganglia [74, 75], lending support to the non-uniformity of the receptor expression patterns. Studies in mammalian brains have shown both spatial and developmental variations in patterns of expression of NMDAR and AMPAR subunits, with some subunits specific for certain brain regions, or variable expression dependent on the stage of development [76, 77].…”

Section: Discussionmentioning

confidence: 77%

Phylogenetic analysis of ionotropic L-glutamate receptor genes in the Bilateria, with special notes on Aplysia californica

2017

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BackgroundThe neurotransmitter L-Glutamate (L-Glu) acting at ionotropic L-Glu receptors (iGluR) conveys fast excitatory signal transmission in the nervous systems of all animals. iGluR-dependent neurotransmission is a key component of the synaptic plasticity that underlies learning and memory. During learning, two subtypes of iGluR, α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR) and N-methyl-D-aspartate receptors (NMDAR), are dynamically regulated postsynaptically in vertebrates. Invertebrate organisms such as Aplysia californica (Aplysia) are well-studied models for iGluR-mediated function, yet no studies to date have analyzed the evolutionary relationships between iGluR genes in these species and those in vertebrates, to identify genes that may mediate plasticity. We conducted a thorough phylogenetic analysis spanning Bilateria to elucidate these relationships. The expression status of iGluR genes in the Aplysia nervous system was also examined.ResultsOur analysis shows that ancestral genes for both NMDAR and AMPAR subtypes were present in the common bilaterian ancestor. NMDAR genes show very high conservation in motifs responsible for forming the conductance pore of the ion channel. The number of NMDAR subunits is greater in vertebrates due to an increased number of splice variants and an increased number of genes, likely due to gene duplication events. AMPAR subunits form an orthologous group, and there is high variability in the number of AMPAR genes in each species due to extensive taxon specific gene gain and loss. qPCR results show that all 12 Aplysia iGluR subunits are expressed in all nervous system ganglia.ConclusionsOrthologous NMDAR subunits in all species studied suggests conserved function across Bilateria, and potentially a conserved mechanism of neuroplasticity and learning. Vertebrates display an increased number of NMDAR genes and splice variants, which may play a role in their greater diversity of physiological responses. Extensive gene gain and loss of AMPAR genes may result in different physiological properties that are taxon specific. Our results suggest a significant role for L-Glu mediated responses throughout the Aplysia nervous system, consistent with L-Glu’s role as the primary excitatory neurotransmitter.Electronic supplementary materialThe online version of this article (doi:10.1186/s12862-016-0871-1) contains supplementary material, which is available to authorized users.

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Physiological evidence that d-aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica neurons

Cited by 10 publications

References 45 publications

Pharmacological evidence that D‐aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica

Pharmacological evidence that D‐aspartate activates a current distinct from ionotropic glutamate receptor currents in Aplysia californica

Behavioral aging is associated with reduced sensory neuron excitability in Aplysia californica

Phylogenetic analysis of ionotropic L-glutamate receptor genes in the Bilateria, with special notes on Aplysia californica

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