Neuroscience
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The therapy of patients suffering the psychiatric disorder schizophrenia requires the usage of antipsychotic drugs that are classified into two different groups, the first-generation (FGAs) and the second-generation antipsychotics (SGAs). This study compares the effects of the two FGAs haloperidol and flupentixol with those of the SGA olanzapine on synapse formation and synaptic activity of embryonic rat hippocampal neurons. To this end, the development of perineuronal nets (PNNs), the formation of synapses and the resulting spontaneous network activity under control and treatment conditions were studied using an indirect co-culture system of neurons and astrocytes in completely defined media. ⋯ Unexpectedly, flupentixol that is regarded as an FGA caused similar effects than the SGA olanzapine in that it augmented synapse number as well as network activity. Our pilot study provides a proof of concept that the neuron-astrocyte co-culture model can be used to investigate the impact of antipsychotics on pivotal parameters of neuronal cell biology. Thereby, it may support the comparative analysis of antipsychotics applied in the therapy of schizophrenia.
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The inferior colliculus (IC), a midbrain structure that processes acoustic information of aversive nature, is distinguished from other auditory nuclei in the brainstem by its connections with structures of the motor system. Previous evidence relating the IC to motor behavior shows that glutamatergic and GABAergic mechanisms in the IC exert influence on systemic haloperidol-induced catalepsy. There is substantial evidence supporting a role played by the endocannabinoid system as a modulator of the glutamatergic neurotransmission, as well as the dopaminergic activity in the basal nuclei and therefore it may be considered as a potential pharmacological target for the treatment of movement disorders. ⋯ Furthermore, the intracollicular administration of AM251 at 100pmol/0.2μl was able to decrease the duration of catalepsy as compared to AM251 at 50pmol/0.2μl- and AM251 at 200pmol/0.2-μl-treated group. The latency for stepping down from the horizontal bar - induced by haloperidol administration - was decreased when microinjection of AEA at 50pmol/0.2μl was preceded with blockade of CB1 receptor with AM251 (100pmol/0.2μl). Our results strengthen the involvement of CB1-signaled endocannabinoid mechanisms of the IC in the neuromodulation of catalepsy induced by systemic administration of the dopaminergic receptors non-selective antagonist haloperidol.
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The theta rhythm is necessary for hippocampal-dependent spatial learning. It has been proposed that each hippocampal stratum can generate a current theta dipole. Therefore, considering that each hippocampal circuit (CA1, CA3, and Dentate Gyrus (DG)) contributes differently to distinct aspects of a spatial memory, the theta oscillations on each stratum and their couplings may exhibit oscillatory dynamics associated with different stages of learning. ⋯ The early acquisition stage of the Morris task was characterized by the predominance of slow frequency theta activity and high coupling between specific hippocampal strata at slow frequencies. However, on the last training day, the theta oscillations were faster in all hippocampal strata, with tighter coupling at fast frequencies between the CA3 pyramidal stratum and other strata. Our results suggest that modifications to the theta frequency and its coupling can be a means by which the hippocampus differentially operates during acquisition and retrieval states.
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Rhynchophylline (RIN) is a significant active component isolated from the Chinese herbal medicine Uncaria rhynchophylla. Several studies have demonstrated that RIN has a significant anticonvulsant effect in many types of epilepsy models in vivo. However, the mechanisms of the anticonvulsant effect remain elusive. ⋯ Whole-cell voltage-clamp recordings indicated that RIN inhibited neuronal hyperexcitability via inhibition of the persistent sodium current (INaP) and NMDA receptor current. Immunofluorescence experiments also demonstrated that RIN rectified the pilocarpine-induced upregulation of Nav1.6 and NR2B protein expression. In conclusion, our results identified RIN as an anticonvulsant agent that inhibited ictal discharge via INap and NMDA receptor current inhibition.
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In spite of the fact that the functional organization of primary visual cortices (V1) differs across species, the dynamic of orientation selectivity is highly structured within neuronal populations. In fact, neurons functionally connect each other in an organized Hebbian process, wherein their wiring and firing are intimately related. Moreover, neuronal ensembles have been suggested to be strongly implicated in sensory processing. ⋯ On the contrary, in mice, the broadly tuned cells displayed higher connectivity index. Second, a significant correlation was found between the connectivity strength and the difference of preferred orientations of neurons for both species. Finally, we observed a systematic adjustment of the connectivity weights within neuronal ensembles in mouse primary visual cortex similarly to the cat V1.