RESUMEN
We used a simple sensory and motor system to investigate the neuronal mechanisms of olfactory orientation behaviour. The main olfactory organs of terrestrial molluscs, the experimental animals used in this work, are located on the tips of their tentacles, which display complex movements when they explore a new environment. By reconstructing the trajectory of the tentacle tip ('nose') movements in three dimensions in freely moving snails, we showed that the protracted tentacles performed continuous scanning, both spontaneously and in response to odours. Odour applications elicited a brief startle-like quiver of the tentacle in a concentration-independent manner as well as a concentration-dependent contraction. Previous work showed that activation of an identified cerebral motoneuron, MtC3, produces tentacle contraction. Here we showed that in semi-intact preparations, MtC3 responded to odours in a concentration-dependent manner, similar to the tentacle contraction response to the same odours in intact animals. This observation suggests that MtC3 is involved in the central control of the scanning area by regulating the tentacle length. Using voltage-sensitive dyes and imaging, we demonstrated that during the hyperpolarizing phases of oscillations in the procerebral lobe, the main olfactory centre of the CNS of terrestrial molluscs, MtC3 spike frequency significantly decreased. We also showed that direct activation of the procerebral lobe resulted in the phasic inhibition of MtC3. This is therefore an example of an olfactory system in which the interaction of oscillatory and single neuronal activity plays an important role in the fine tuning of orientation behaviour to suit the particular odour environment.
Asunto(s)
Caracoles Helix/fisiología , Neuronas/fisiología , Orientación/fisiología , Olfato/fisiología , Animales , Calcio/metabolismo , Colorantes , Señales (Psicología) , Electrofisiología , Microelectrodos , Neuronas Motoras/fisiología , Movimiento/fisiología , Odorantes , Órganos de los Sentidos/fisiologíaRESUMEN
We investigated the influence of the protein synthesis blocker anisomycin on contextual memory in the terrestrial snail Helix. Prior to the training session, the behavioral responses in two contexts were similar. Two days after a session of electric shocks (5 d) in one context only, the context conditioning was observed as the significant difference of behavioral response amplitudes in two contexts. On the day following testing of context learning, a session of "reminding" was performed, immediately after which the snails were injected with anisomycin or vehicle. Testing of long-term context memory has shown that only anisomycin injections impaired the context conditioning. In control series, the snails were injected after the training session with anisomycin/saline without reminding, and no impairment of the long-term context memory was observed, while injection of anisomycin during the training session completely abolished the long-term memory. No effects of anisomycin on the short-term memory were observed. Surprisingly, injection of anisomycin after the reminding combined with reinforcing stimuli elicited no effect on the context memory. Differences between single-trial and multisession learning are discussed.
Asunto(s)
Aprendizaje por Asociación/fisiología , Reacción de Prevención/fisiología , Caracoles Helix/metabolismo , Memoria/fisiología , Biosíntesis de Proteínas/fisiología , Animales , Anisomicina/farmacología , Aprendizaje por Asociación/efectos de los fármacos , Reacción de Prevención/efectos de los fármacos , Ambiente , Caracoles Helix/efectos de los fármacos , Memoria/efectos de los fármacos , Biosíntesis de Proteínas/efectos de los fármacos , Inhibidores de la Síntesis de la Proteína/farmacologíaRESUMEN
A large body of evidence implicates beta-amyloid peptide (betaAP) and other derivatives of the evolutionarily highly conserved amyloid precursor protein (APP) in the pathogenesis of Alzheimer's disease. However, the functional relationship of APP and its proteolytic derivatives to synaptic plasticity is not well known. We demonstrate that 30 min exposure to the 25-35 fragment of betaAP do not markedly change the dynamics of synaptic responses in identified neurons of terrestrial snail while a significant decrease of long-term sensitization was observed after 180 min betaAP bath application. In the behavioral experiments, a significant reduction of sensitization, and decreased ability to develop food-aversion conditioning was observed after betaAP injection. Our results clearly demonstrate that the neurotoxic 25-35 fragment of betaAP may play a significant role in behavioral plasticity by chronically eliminating certain underlying forms of synaptic plasticity. The study also proposes a novel invertebrate model to Alzheimer's disease.
Asunto(s)
Péptidos beta-Amiloides/farmacología , Caracoles Helix/efectos de los fármacos , Sistema Nervioso/efectos de los fármacos , Plasticidad Neuronal/efectos de los fármacos , Sinapsis/efectos de los fármacos , Transmisión Sináptica/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Animales , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Secuencia Conservada/fisiología , Modelos Animales de Enfermedad , Evolución Molecular , Potenciales Postsinápticos Excitadores/efectos de los fármacos , Potenciales Postsinápticos Excitadores/fisiología , Ganglios de Invertebrados/efectos de los fármacos , Ganglios de Invertebrados/metabolismo , Ganglios de Invertebrados/fisiopatología , Caracoles Helix/fisiología , Sistema Nervioso/metabolismo , Sistema Nervioso/fisiopatología , Plasticidad Neuronal/fisiología , Fragmentos de Péptidos/metabolismo , Fragmentos de Péptidos/farmacología , Sinapsis/fisiología , Transmisión Sináptica/fisiología , Factores de TiempoRESUMEN
Despite the clinical efficacy of the most thoroughly studied conventional neuroleptic agent haloperidol, and the atypical antipsychotic risperidone is well established, little information is available on their molecular effects. Recent advances in high-density DNA microarray techniques allow the possibility to analyze thousands of genes simultaneously for their differential gene expression patterns in various biological processes, and to determine mechanisms of drug action. The aim of this series of experiments was to gain experience in antipsychotic gene-expression profiling and characterize (in the parlance of genomics) the "antipsychotic transcriptome." In this prospective animal study, broad-scale gene expression profiles were characterized for brains of rats treated with antipsychotics and compared with those of sham controls. We used DNA microarrays containing 8000 sequences to measure the expression patterns of multiple genes in rat fronto-temporo-parietal cortex after intraperitoneal treatment with haloperidol or risperidone. A number of transcripts were differentially expressed between control and treated samples, of which only 36 and 89 were found to significantly differ in expression as a result of exposure to haloperidol or risperidone, respectively (P<0.05). Acutely, 13 genes were more highly expressed and 15 transcripts were found to be significantly less abundant, whereas chronically nine genes were up-regulated and none of them was repressed in haloperidol-treated cortices. Risperidone acutely induced 43 and repressed 46 genes, and chronically over-expressed 6 and down-regulated 11 transcripts. Selected genes were assayed by real-time PCR, then normalized to beta-actin. These assays confirmed the significance of the array results for all transcripts tested. Despite their differing receptor affinity and selectivity, our findings indicate that haloperidol and risperidone interfere with cell survival, neural plasticity, signal transduction, ionic homeostasis and metabolism in a similar manner.