Neuroscience
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Rivastigmine is a non-competitive inhibitor of both acetylcholinesterase (AChE) and butylcholinesterase (BuChE) used to treat mild to moderate dementia in Alzheimer's disease (AD) patients. Although rivastigmine reportedly ameliorates cognitive dysfunction in these patients, its ability to improve Behavioral and Psychological Symptoms of Dementia (BPSD) remains unclear. To determine whether rivastigmine treatment antagonizes depression-like behaviors, we chronically administered rivastigmine (0.1-1.0mg/kg) to olfactory bulbectomized (OBX) mice once a day for 2weeks, starting 2weeks after bulbectomy. ⋯ These effects were blocked by WAY-100635 but not ketanserin treatment. Finally, we confirmed that 5-HT1A but not 5-HT2A receptor stimulation by specific agonists mimicked rivastigmine-induced anti-depression activity and promoted hippocampal neurogenesis. We conclude that, in addition to enhancing the cholinergic system, rivastigmine treatment restores normal function of the hippocampal serotonergic system, an activity that likely ameliorates depressive behaviors in AD patients.
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A spinal generator for ejaculation (SGE) has been identified in the rat that orchestrates peripheral events leading to ejaculation. Despite physiological evidence of cerebral influences exerted on the SGE, brain-descending pathways to the SGE have not been fully delineated. A tracing study combining retrograde and anterograde approaches was undertaken in adult male rats in order to identify brain sites containing neurons that directly project onto SGE neurons. ⋯ Galanin and substance P receptor (NK1) were used as markers of SGE neurons. DA-positive fibers and varicosities originating in the targeted brain sites were found to make close appositions with neurons expressing galanin or NK1 receptors in central medial gray of L3-L4 spinal segments. This study provides new insights regarding the anatomical support for the brain control of ejaculation via direct influences onto the SGE.
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N-methyl-d-aspartate receptors (NMDARs) at layer (L)1/primary whisker motor cortex synaptic inputs are distinct from thalamic/striatal (Str) synaptic inputs onto L5 pyramidal neurons in the rat somatosensory cortex. However, the consequences of differential expression of putative GluN3A-containing triheteromeric NMDARs at L1 inputs and GluN2A-containing diheteromeric NMDARs at Str inputs on plasticity of the underlying synapses at the respective inputs remain unknown. Here we demonstrate that L1, but not Str, synapses are potentiated following delta burst stimulation (dBS). ⋯ Our data suggest distinct potentiating paradigms for the two convergent inputs onto pyramidal neurons in the somatosensory cortex and co-dependence of synaptic potentiation on brain wave-tuned frequencies of burst stimulation and subunit composition of underlying NMDARs. A model for predicting the likelihood of enhancing synaptic efficacy is proposed based on Ca(2+) influx through these receptors and integration of EPSPs at these inputs. Together, these findings raise the possibility of input-specific enhancements of synaptic efficacy in neurons as a function of the animal's behavioral state and/or arousal in vivo.
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Some pathophysiological models of schizophrenia posit that prenatal inflammation sensitizes the developing brain to second insults in early life and enhances brain vulnerability, thereby increasing the risk of developing the disorder during adulthood. We previously developed a two-hit animal model, based on the well-established prenatal immune challenge with poly-inosinic/cytidylic acid (polyI:C), followed by juvenile restraint stress (RS). We observed an additive disruption of prepulse inhibition (PPI) of acoustic startle in juvenile mice submitted to both insults. ⋯ The reversal effect of α-lipoic acid pretreatment on these behavioral alterations was further accompanied by a normalization of the associated oxidative status and dopaminergic and GABAergic abnormalities in the prefrontal cortex. Based on our double insult paradigm, these results support the hypothesis that oxidative stress plays an important role in the development of PPI deficits, a well-known behavior associated with schizophrenia. These findings form the basis of future studies aiming to unravel mechanistic insights of the putative role of antioxidants in the treatment of schizophrenia, especially during the prodromal stage.
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Previous studies have indicated a sparse distribution of multisensory neurons in the transition zones between cortical areas associated with specific sensory modalities. However, little is known about the distribution and functional properties of such neurons. The bimodal visual-auditory neurons in the transition area between visual and auditory cortices in rats were examined to determine whether these neurons are modulated by simultaneous input from visual and auditory modalities. ⋯ Exposing adult animals to combined visual and auditory stimuli resulted in an expansion of bimodal neuron distribution in the visual-auditory transition area. These effects were more pronounced in young animals; in this case, the distribution of visual-auditory neurons extended past the limits of the transition area and invaded the flanking modality-specific cortical areas. These results provide a direct demonstration of the role of sensory experience in shaping cortical structure, which can have implications for neuronal integration and cognitive function.