Retinoic acid reduces the formation of, and acutely modulates, invertebrate electrical synapses.

Communication between cells in the nervous system is dependent on both chemical and electrical synapses. Factors that can affect chemical synapses have been well studied, but less is known about factors that influence electrical synapses. Retinoic acid, the vitamin A metabolite, is a known regulator of chemical synapses, but few studies have examined its capacity to regulate electrical synapses.

Non-canonical retinoid signaling in neural development, regeneration and synaptic function.

Canonical retinoid signaling via nuclear receptors and gene regulation is critical for the initiation of developmental processes such as cellular differentiation, patterning and neurite outgrowth, but also mediates nerve regeneration and synaptic functions in adult nervous systems. In addition to canonical transcriptional regulation, retinoids also exert rapid effects, and there are now multiple lines of evidence supporting non-canonical retinoid actions outside of the nucleus, including in dendrites and axons. Together, canonical and non-canonical retinoid signaling provide the precise temporal and spatial control necessary to achieve the fine cellular coordination required for proper nervous system function.

Disruptions in network plasticity precede deficits in memory following inhibition of retinoid signaling.

Retinoic acid, the active metabolite of vitamin A, is important for vertebrate cognition and hippocampal plasticity, but few studies have examined its role in invertebrate learning and memory, and its actions in the invertebrate central nervous system are currently unknown. Using the mollusc , we examined operant conditioning of the respiratory behavior, controlled by a well-defined central pattern generator (CPG), and used citral to inhibit retinoic acid signaling. Both citral- and vehicle-treated animals showed normal learning, but citral-treated animals failed to exhibit long-term memory at 24 h.

Molluscan RXR Transcriptional Regulation by Retinoids in a CNS Organ Culture System.

Retinoic acid, the active metabolite of Vitamin A, is important for the appropriate development of the nervous system (e.g., neurite outgrowth) as well as for cognition (e.

Activity-dependent modulation of neuronal K channels by retinoic acid enhances Ca channel activity.

The metabolite of vitamin A, retinoic acid (RA), is known to affect synaptic plasticity in the nervous system and to play an important role in learning and memory. A ubiquitous mechanism by which neuronal plasticity develops in the nervous system is through modulation of voltage-gated Ca (Ca) and voltage-gated K channels. However, how retinoids might regulate the activity of these channels has not been determined.

Context-Dependent Role of miR-124 in Retinoic Acid-Induced Growth Cone Attraction of Regenerating Motorneurons.

During development and regeneration, growth cones at the tips of extending axons navigate through a complex environment to establish accurate connections with appropriate targets. Growth cones can respond rapidly to classical and non-classical guidance cues in their environment, often requiring local protein synthesis. In vertebrate growth cones, local protein synthesis in response to classical cues can require regulation by microRNAs (miRNAs), a class of small, conserved, non-coding RNAs that post-transcriptionally regulate gene expression.

Early Metazoan Origin and Multiple Losses of a Novel Clade of RIM Presynaptic Calcium Channel Scaffolding Protein Homologs.

The precise localization of CaV2 voltage-gated calcium channels at the synapse active zone requires various interacting proteins, of which, Rab3-interacting molecule or RIM is considered particularly important. In vertebrates, RIM interacts with CaV2 channels in vitro via a PDZ domain that binds to the extreme C-termini of the channels at acidic ligand motifs of D/E-D/E/H-WC-COOH, and knockout of RIM in vertebrates and invertebrates disrupts CaV2 channel synaptic localization and synapse function. Here, we describe a previously uncharacterized clade of RIM proteins bearing domain architectures homologous to those of known RIM homologs, but with some notable differences including key amino acids associated with PDZ domain ligand specificity.

Inhibition of Rho GTPases in Invertebrate Growth Cones Induces a Switch in Responsiveness to Retinoic Acid.

During development, growth cones are essential for axon pathfinding by sensing numerous guidance cues in their environment. Retinoic acid, the metabolite of vitamin A, is important for neurite outgrowth during vertebrate development, but may also play a role in axon guidance, though little is known of the cellular mechanisms involved. Our previous studies showed that retinoid-induced growth cone turning of invertebrate motorneurons requires local protein synthesis and calcium influx.

Retinoid receptor-based signaling plays a role in voltage-dependent inhibition of invertebrate voltage-gated Ca channels.

The retinoic acid receptor (RAR) and retinoid X receptor (RXR) mediate the cellular effects of retinoids (derivatives of vitamin A). Both RAR and RXR signaling events are implicated in hippocampal synaptic plasticity. Furthermore, retinoids can interact with calcium signaling during homeostatic plasticity.

Pharmacological evidence for the role of RAR in axon guidance and embryonic development of a protostome species.

Retinoic acid (RA), the active metabolite of vitamin A, functions through nuclear receptors, one of which is the retinoic acid receptor (RAR). Though the RAR is essential for various aspects of vertebrate development, little is known about the role of RAR in nonchordate invertebrates. Here, we examined the potential role of an invertebrate RAR in mediating chemotropic effects of retinoic acid.

Identification and Characterization of microRNAs during Retinoic Acid-Induced Regeneration of a Molluscan Central Nervous System.

Retinoic acid (RA) is the biologically active metabolite of vitamin A and has become a well-established factor that induces neurite outgrowth and regeneration in both vertebrates and invertebrates. However, the underlying regulatory mechanisms that may mediate RA-induced neurite sprouting remain unclear. In the past decade, microRNAs have emerged as important regulators of nervous system development and regeneration, and have been shown to contribute to processes such as neurite sprouting.

Retinoid X receptor α downregulation is required for tail and caudal spinal cord regeneration in the adult newt.

Some adult vertebrate species, such as newts, axolotls and zebrafish, have the ability to regenerate their central nervous system (CNS). However, the factors that establish a permissive CNS environment for correct morphological and functional regeneration in these species are not well understood. Recent evidence supports a role for retinoid signaling in the intrinsic ability of neurons, in these regeneration-competent species, to regrow after CNS injury.

Retinoic acid inhibits neuronal voltage-gated calcium channels.

Retinoic acid is the active metabolite of vitamin A and regulates several important cellular processes by activating retinoic acid receptors (RAR) and retinoid X receptors (RXR). These receptors generally act as transcription factors, though non-genomic actions of both retinoic acid and the receptors have also been reported. One such nongenomic effect includes the modulation of Ca levels during homeostatic synaptic plasticity in the hippocampus.

The effect of rearing environment on memory formation.

is a well-studied model system for determining how changes in the environment influence associative learning and memory formation. For example, some wild strains of , collected from separate geographic locations, show superior memory-forming abilities compared with others. Here, we studied memory formation in two laboratory-bred strains, derived from the same original population in The Netherlands.

The role of retinoic acid in the formation and modulation of invertebrate central synapses.

Unlabelled: Trophic factors can influence many aspects of nervous system function, such as neurite outgrowth, synapse formation, and synapse modulation. The vitamin A metabolite, retinoic acid, can exert trophic effects to promote neuronal survival and outgrowth in many species and is also known to modulate vertebrate hippocampal synapses. However, its role in synaptogenesis has not been well studied, and whether it can modulate existing invertebrate synapses is also not known.

Extending the duration of long-term memories: Interactions between environmental darkness and retinoid signaling.

Retinoid signaling plays an important role in hippocampal-dependent vertebrate memories. However, we have previously demonstrated that retinoids are also involved in the formation of long-term implicit memory following operant conditioning of the invertebrate mollusc Lymnaea stagnalis. Furthermore, we have discovered an interaction between environmental light/dark conditions and retinoid signaling and the ability of both to convert intermediate-term memory into long-term memory.

Expression of a retinoic acid receptor (RAR)-like protein in the embryonic and adult nervous system of a protostome species.

The vitamin A metabolite, retinoic acid, is an important molecule in nervous system development and regeneration in vertebrates. Retinoic acid signaling in vertebrates is mediated by two classes of nuclear receptors, the retinoid X receptors (RXRs) and the retinoic acid receptors (RARs). Recently, evidence has emerged to suggest that many effects of retinoic acid are conserved between vertebrate and invertebrate nervous systems, even though the RARs were previously thought to be a vertebrate innovation and to not exist in non-chordates.

Retinoic acid affects calcium signaling in adult molluscan neurons.

Retinoic acid, the active metabolite of vitamin A, is important for nervous system development, regeneration, as well as cognitive functions of the adult central nervous system. These central nervous system functions are all highly dependent on neuronal activity. Retinoic acid has previously been shown to induce changes in the firing properties and action potential waveforms of adult molluscan neurons in a dose- and isomer-dependent manner.

Novel interactive effects of darkness and retinoid signaling in the ability to form long-term memory following aversive operant conditioning.

The vitamin A metabolite, retinoic acid, is important for memory formation and hippocampal synaptic plasticity in vertebrate species. In our studies in the mollusc Lymnaea stagnalis, we have shown that retinoic acid plays a role in memory formation following operant conditioning of the aerial respiratory behaviour. Inhibition of either retinaldehyde dehydrogenase (RALDH) or the retinoid receptors prevents long-term memory (LTM) formation, whereas synthetic retinoid receptor agonists promote memory formation by converting intermediate-term memory (ITM) into LTM.

Retinoid signaling is necessary for, and promotes long-term memory formation following operant conditioning.

Retinoic acid, a metabolite of vitamin A, is proposed to play an important role in vertebrate learning and memory, as well as hippocampal-dependent synaptic plasticity. However, it has not yet been determined whether retinoic acid plays a similar role in learning and memory in invertebrates. In this study, we report that retinoid signaling in the mollusc Lymnaea stagnalis, is required for long-term memory formation following operant conditioning of its aerial respiratory behaviour.

Retinoic acid induces changes in electrical properties of adult neurons in a dose- and isomer-dependent manner.

The electrical activity of neurons is known to play a role in neuronal development, as well as repair of adult nervous tissue. For example, the extension of neurites and motility of growth cones can be modulated by changes in the electrical firing of neurons. The vitamin A metabolite retinoic acid also plays a critical role during nervous system development and is also known to elicit regenerative responses, namely the induction, enhancement, and directionality of neurite outgrowth.

Presence of Ribeiroia ondatrae in the developing anuran limb disrupts retinoic acid levels.

The widespread reports of malformed frogs have sparked interest worldwide to try and determine the causes of such malformations. Ribeiroia ondatrae is a digenetic trematode, which has been implicated as one such cause, as this parasite encysts within the developing tadpole hind limb bud and inguinal region causing dramatic limb malformations. Currently, the mechanisms involved in parasite-induced limb deformities remain unclear.

Developmental expression of a molluscan RXR and evidence for its novel, nongenomic role in growth cone guidance.

It is well known that the vitamin A metabolite, retinoic acid, plays an important role in vertebrate development and regeneration. We have previously shown that the effects of RA in mediating neurite outgrowth, are conserved between vertebrates and invertebrates (Dmetrichuk et al., 2005, 2006) and that RA can induce growth cone turning in regenerating molluscan neurons (Farrar et al.

A novel, nongenomic mechanism underlies retinoic acid-induced growth cone turning.

The vitamin A metabolite, retinoic acid (RA), is well known for its roles in neural development and regeneration. We have previously shown that RA can induce positive growth cone turning in regenerating neurons in vitro. In this study, we address the subcellular mechanisms underlying this chemo-attractive response, using identified central neurons from the adult mollusc, Lymnaea stagnalis.