Neuroscience
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The dorsomedial striatum (DMS) has been implicated in the acquisition of reward representations, a proposal leading to the hypothesis that it should play a role in situations involving reward loss. We report the results of an experiment in which the effects of DMS excitotoxic lesions were tested in consummatory successive negative contrast (reward devaluation), autoshaping training with partial vs. continuous reinforcement (reward uncertainty), and appetitive extinction (reward omission). Animals with DMS lesions exhibited reduced lever pressing responding, but enhanced goal entries, during partial reinforcement training in autoshaping. ⋯ Thus, DMS lesions selectively affected the behavioral adjustment to a situation involving reward uncertainty, producing a behavioral reorganization according to which goal tracking (goal entries) became predominant at the expense of sign tracking (lever pressing). This pattern of results shows that the function of the DMS in situations involving reward loss is not general, but restricted to reward uncertainty. We suggest that a nonassociative, drive-related process induced by reward uncertainty requires normal output from DMS neurons.
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Hypoxic circumstances result in functional and structural impairments of the brain. Oxygen-glucose deprivation (OGD) on hippocampal slices is a technique widely used to investigate the consequences of ischemic stroke and the potential neuroprotective effects of different drugs. Acetyl-l-carnitine (ALC) is a naturally occurring substance in the body, and it can therefore be administered safely even in relatively high doses. ⋯ A further aim was to investigate the mechanism underlying the protective effect of this compound. The experiments revealed that ALC is neuroprotective against OGD in a dose-dependent manner, which is manifested not only in the regeneration of the impaired synaptic transmission after the OGD, but also in the inducibility and stability of the LTP. In the case of the most effective concentration of ALC (500μM), use of a phosphoinositide 3-kinase (PI3K) inhibitor (LY294002) revealed that the PI3K/Akt signaling pathway has a key role in the restoration of the synaptic transmission and plasticity reached by ALC treatment.
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In experimental animal models of auditory hair cell (HC) loss, insults such as noise or ototoxic drugs often lead to secondary changes or degeneration in non-sensory cells and neural components, including reduced density of spiral ganglion neurons, demyelination of auditory nerve fibers and altered cell numbers and innervation patterns in the cochlear nucleus (CN). However, it is not clear whether loss of HCs alone leads to secondary degeneration in these neural components of the auditory pathway. To elucidate this issue, we investigated changes of central components after cochlear insults specific to HCs using diphtheria toxin receptor (DTR) mice expressing DTR only in HCs and exhibiting complete HC loss when injected with diphtheria toxin (DT). ⋯ In contrast, noise exposure induced significant changes in synapses, myelin and CN organization even without loss of inner HCs. We observed a decrease of neuronal size in the auditory pathway, including peripheral axons, spiral ganglion neurons, and CN neurons, likely due to loss of input from the cochlea. Taken together, selective HC ablation and noise exposure showed different patterns of pathology in the auditory pathway and the presence of HCs is not essential for the maintenance of central synaptic connectivity and myelination.
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Amitriptyline (AMI), a commonly prescribed tricyclic antidepressant (TCA) to parkinsonian patients, specifically showed a significant delay in dopaminergic therapy initiation and improvement in motor disability in parkinsonian patients. Moreover, it was recently shown that AMI has neuroprotective properties; however, the mechanisms underlying this effect in Parkinson's disease (PD) are not fully understood. The current study aimed to investigate the possible neuroprotective mechanisms afforded by AMI in the rotenone model of PD and to assess whether another TCA member, imipramine (IMI), shows a corresponding effect. ⋯ Pretreatment of rotenone groups with AMI or IMI prevented rotenone-induced neuronal degeneration and increased striatal dopamine level with motor recovery. These effects were accompanied by restoring striatal monoamines and brain-derived neurotrophic factor levels, as well as reducing oxidative damage, microglial activation and expression of proinflammatory cytokines and inducible nitric oxide synthase. The present results suggest that modulation of noradrenaline and serotonin levels, up-regulation of neurotrophin, inhibition of glial activation, anti-oxidant and anti-inflammatory activities could serve as important mechanisms underlying the neuroprotective effects of the used drugs in the rotenone model of PD.
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A loud auditory stimulus (LAS) presented simultaneously with a visual imperative stimulus can reduce reaction time (RT) by automatically triggering a movement prepared in the brain and has been used to investigate a movement preparation. It is still under debate whether or not a response is prepared in advance in RT tasks involving choice responses. The purpose of the present study was to investigate the preparatory state of anticipatory postural adjustments (APAs) during a choice reaction step initiation. ⋯ This observation suggests that APAs are prepared in advance and withheld from release until the appropriate timing during a choice reaction step initiation. The preparatory activity of APAs might be modulated by the inhibitory activity required by the choice tasks. The preparation strategy may be chosen for fast responses and is judged most suitable to comply with the tasks because inappropriately initiated APAs can be corrected without making complete stepping errors.