Brain structure & function
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Comparative Study
Brain grey matter deficits in smokers: focus on the cerebellum.
Structural cerebral deficiencies in smokers have been well characterized by morphometric investigations focussing on cortical and subcortical structures. Although the role of the cerebellum is increasingly noted in mental and addiction disorders, no reports exist regarding cerebellar alterations in smokers employing a methodology specifically designed to assess the cerebellar morphology. We acquired high-resolution MRI scans from 33 heavy smokers and 22 never-smokers and used a voxel-based morphometry (VBM) approach utilizing the Spatially Unbiased Infratentorial (SUIT) toolbox (Diedrichsen 2006) to provide an optimized and fine-grained exploration of cerebellar structural alterations associated with smoking. ⋯ The grey matter volume in Crus I correlated negatively with the amount of nicotine dependence as assessed by means of the Fagerström scale. Since Crus I has been identified as the cognitive division of the cerebellum, the structural deficit may in part mediate cognitive deficits previously reported in smokers. Of note, the dependence-related magnitude of the volume deficit may support the notion that the cerebellum is substantially involved in core mechanisms of drug dependence.
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The proper organization and function of GABAergic interneuron networks is essential for many cognitive processes and abnormalities in these systems have been documented in schizophrenic patients. The memory function of the hippocampus depends on two major patterns of oscillations in the theta and gamma ranges, both requiring the intact functioning of the network of fast-firing interneurons expressing parvalbumin. We examined the ability of acute and chronic administration of NMDA receptor (NMDA-R) antagonists to recapitulate the oscillatory dysfunctions observed in schizophrenia. ⋯ Chronic administration of ketamine also leads to decrease in the number of detectable parvalbumin interneurons. Histological examination of interindividual differences indicated, however, that within the ketamine treated group a further decrease in parvalbumin neurons correlated with strengthening of oscillations. The findings are consistent with abnormalities of oscillations in human schizophrenia and further validate the NMDA-R hypofunction hypothesis.
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The nucleus reuniens (RE) of the midline thalamus has been shown to strongly innervate structures of the limbic forebrain, prominently including the hippocampus (HF) and the medial prefrontal cortex (mPFC) and to exert pronounced excitatory effects on HF and mPFC. It was unknown, however, whether RE projections to, and hence actions on, the HF and mPFC originate from a common or largely separate groups of RE neurons. Using fluorescent retrograde tracing techniques, we examined the patterns of distribution of RE cells projecting to HF, to the mPFC or to both sites via axon collaterals. ⋯ Depending on specific combinations of injections, double labeled cells ranged from approximately 3-9% of the labeled neurons. The nucleus reuniens has been shown to be a vital link in limbic subcortical-cortical communication and recent evidence indicates a direct RE involvement in hippocampal and medial prefrontal cortical-dependent behaviors. The present findings indicate that RE is critically positioned to influence the HF and mPFC, and their associated behaviors, via separate or collateral projections to these sites.
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Oscillation activities are the feature of neural network and correlated to different physiological states. The theta (θ) oscillation (2-7 Hz) has been reported in the basal ganglia, and the intrinsic resonance properties of individual neurons have provided a basis for this network oscillation. The basal ganglia neurons receive comprehensive modulation arising from dopaminergic (DA) neurons located in the substantia nigra pars compacta (SNc), but how the oscillation is regulated in SNc DA neurons remains poorly understood. ⋯ Further investigation demonstrated two individual components: (1) SK-current generated resonance at around -65 mV, which could be blocked by apamin (300 nM), a specific antagonist of the small-conductance calcium-dependent potassium channel; (2) h-current (I (h)) generated resonance at around -75 mV, which could be abolished by ZD7288 (10 μM), a selective blocker of HCN channels. We concluded that in SNc DA neurons, θ resonance was mediated by two distinct ionic channels at hyperpolarized potentials. Our results imply that θ frequency resonance of individual SNc DA neurons may participate in coordinating rhythmic firing activity and contribute to the physiological or pathophysiological behaviors of Parkinson's disease.