Neuropharmacology and behavior in planarians: Translations to mammals

Buttarelli, Francesca Romana; Pellicano, Clelia; Pontieri, Francesco E.

doi:10.1016/j.cbpc.2008.01.009

Cited by 95 publications

(90 citation statements)

References 75 publications

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“…The planarian has a centralized brain that guides behavior (Buttarelli et al, 2008;Sarnat and Netsky, 1985), and it is hard to imagine how memory traces (not just reflex arcs mediated by central pattern generators) can be encoded and stored in tissues remaining after complete head removal. However, such results are now made more plausible by modern discoveries such as epigenetic modification, which occurs in many cell types, not just the CNS (Arshavsky, 2006;Day and Sweatt, 2010;Ginsburg and Jablonka, 2009;Levenson and Sweatt, 2005;Zovkic et al, 2013) and RNAi (Smalheiser et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…Free-living, planarian flatworms represent the 'first' class of organism to have a centralized brain with true synaptic transmission (Sarnat and Netsky, 1985), and share the majority of neurotransmitters that occur in vertebrate brains (Buttarelli et al, 2008). Planarians have primitive eyes and other sensory capabilities, including sensitivity to chemical gradients (Mason, 1975;Miyamoto and Shimozawa, 1985), vibration (Dessì Fulgheri and Messeri, 1973), electric fields and magnetic fields (Brown and Chow, 1975;Brown, 1966).…”

Section: Introductionmentioning

confidence: 99%

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An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

Shomrat

Levin

2013

Journal of Experimental Biology

102

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SUMMARYPlanarian flatworms are a popular system for research into the molecular mechanisms that enable these complex organisms to regenerate their entire body, including the brain. Classical data suggest that they may also be capable of long-term memory. Thus, the planarian system may offer the unique opportunity to study brain regeneration and memory in the same animal. To establish a system for the investigation of the dynamics of memory in a regenerating brain, we developed a computerized training and testing paradigm that avoided the many issues that confounded previous, manual attempts to train planarians. We then used this new system to train flatworms in an environmental familiarization protocol. We show that worms exhibit environmental familiarization, and that this memory persists for at least 14days -long enough for the brain to regenerate. We further show that trained, decapitated planarians exhibit evidence of memory retrieval in a savings paradigm after regenerating a new head. Our work establishes a foundation for objective, high-throughput assays in this molecularly tractable model system that will shed light on the fundamental interface between body patterning and stored memories. We propose planarians as key emerging model species for mechanistic investigations of the encoding of specific memories in biological tissues. Moreover, this system is likely to have important implications for the biomedicine of stem-cell-derived treatments of degenerative brain disorders in human adults. Supplementary material available online at

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

Shomrat

Levin

2013

Journal of Experimental Biology

102

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“…As cancer and tissue regeneration are often linked in the literature (Oviedo and Beane 2009), flatworms are also put forward as model systems to assess genotoxicity (Guecheva et al 2001;Kalafatic et al 2004) and carcinogenicity (Best and Morita 1993;Schaeffer 1993b), and in experiments in teratology and eco-toxicology (Indeherberg et al 1999;Preza and Smith 2001;Navarro et al 2009). Among the many advantages of flatworms, such as their ease of culture in the laboratory and sensitivity to low concentrations of environmental toxins (Nano et al 2002), previous research has also demonstrated that their cellular and physiological responses are similar to those in mammals (Hall et al 1986;Schaeffer 1993a;Buttarelli et al 2008).…”

Section: Introductionmentioning

confidence: 95%

“…Traditionally, they are used as models in studies concerning regeneration (Egger et al 2006;Eisenhoffer et al 2008;Janicke and Scharer 2009;Petersen and Reddien 2008;Umesono and Agata 2009). They are also suggested for neuropharmacology drug screening (Buttarelli et al 2008;Rawls et al 2010) and aging studies (Mouton et al 2009). Moreover these animals are subjects of studies on evolutionary biology of sexual reproduction (Janicke and Scharer 2009).…”

Section: Introductionmentioning

confidence: 99%

Reference genes for qPCR assays in toxic metal and salinity stress in two flatworm model organisms

et al. 2011

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The flatworm species Schmidtea mediterranea and Macrostomum lignano have become new and innovative model organisms in stem cell, regeneration and tissue homeostasis research. Because of their unique stem cell system, (lab) technical advantages and their phylogenetic position within the Metazoa, they are also ideal candidate model organisms for toxicity assays. As stress and biomarker screenings are often performed at the transcriptional level, the aim of this study was to establish a set of reference genes for qPCR experiments for these two model organisms in different stress situations. We examined the transcriptional stability of nine potential reference genes (actb, tubb, ck2, cox4, cys, rpl13, gapdh, gm2ap, plscr1) to assess those that are most stable during altered stress conditions (exposure to carcinogenic metals and salinity stress). The gene expression stability was evaluated by means of geNorm and NormFinder algorithms. Sets of best reference genes in these analyses varied between different stress situations, although gm2ap and actb were stably transcribed during all tested combinations. In order to demonstrate the impact of bad normalisation, the stress-specific gene hsp90 was normalised to different sets of reference genes. In contrast to the normalisation according to GeNorm and NormFinder, normalisation of hsp90 in Macrostomum lignano during cadmium stress did not show a significant difference when normalised to only gapdh. On the other hand an increase of variability was noticed when normalised to all nine tested reference genes together. Testing appropriate reference genes is therefore strongly advisable in every new experimental condition.

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“…Planarians possess many of the neurotransmitter systems present in vertebrates [1] and are the most primitive example of cephalization in the animal kingdom, displaying a true brain, sometimes referred to as cephalic ganglia [2].…”

Section: Introductionmentioning

confidence: 99%

Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians

et al. 2015

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Planarians are rapidly developing into very useful research subjects in pharmacology and neuroscience research. Here we report that curare, a cholinergic nicotinic receptor antagonist, alleviates the nicotine-induced planarian seizure-like movements (pSLM) by up to 50 % at equimolar concentrations of nicotine and curare (1 mM), while curare alone does not induce significant pSLMs. The simplest interpretation of our data is that there are nicotine induced behaviors insensitive to curare in our experimental organism. To the best of our knowledge, this is the first report on curare-insensitive, nicotine-induced effects in any organism.

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Neuropharmacology and behavior in planarians: Translations to mammals

Cited by 95 publications

References 75 publications

An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

An automated training paradigm reveals long-term memory in planaria and its persistence through head regeneration

Reference genes for qPCR assays in toxic metal and salinity stress in two flatworm model organisms

Evidence of Nicotine-Induced, Curare-Insensitive, Behavior in Planarians

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