A role of the basal ganglia in the occurrence of visual hallucinations (a hypothetical mechanism)

A hypothetical mechanism of the basal ganglia involvement in visual hallucinations is proposed. According to this mechanism, hallucination is the result of modulation of the efficacy of corticostriatal synaptic inputs and changes in spiny cell activity due to the rise of striatal dopamine concentration (or due to other reasons). These changes cause an inhibition of neurons in the substantia nigra pars reticulata and subsequent disinhibition of neurons in the superior colliculus and pedunculopontine nucleus (including its cholinergic cells). In the absence of afferentation from the retina this disinhibition leads to activation of neurons in the lateral geniculate nucleus, pulvinar and other thalamic nuclei projecting to the primary and highest visual cortical areas, prefrontal cortex, and also back to the striatum. Hallucinations as conscious visual patterns are the result of selection of signals circulating in several interconnected loops each of which includes one of above mentioned neocortical areas, one of thalamic nuclei, limbic and one of visual areas of the basal ganglia, superior colliculus and/or pedunculopontine nucleus. According to our model, cannabinoids, opioids and ketamine may lead to hallucinations due to their promotional role in the LTD of cortical inputs to GABAergic spiny cells of striatal striosomes projecting to dopaminergic neurons, disinhibition of the lasts, and increase in striatal dopamine concentration.     

特发性基底节钙化致病的分子机制

特发性基底节钙化(Idiopathic basal ganglia calcification, IBGC)俗称Fahr病,是一种以基底节及大脑其他部位钙化为特征的神经系统遗传疾病,患者可出现运动障碍及认知、精神异常,目前尚无有效治疗药物。该病具有遗传异质性,自2012年本课题组发现第一个致病基因SLC20A2以来,现今又发现4个该病的致病基因：PDGFRB,PDGFB,ISG15和XPR1,初步将IBGC的发生机制分别与大脑局部无机磷稳态失衡、血脑屏障功能障碍及IFN-α/β免疫信号过度放大联系起来。文章综述了IBGC的遗传学研究进展,初步探讨了不同基因导致IBGC的分子机理。     

Thermophysiology of the paradoxical sleep

Data on interactions between the paradoxical sleep (PS) and thermoregulation under thermo-comfortable and extreme conditions (in high and low temperatures, forced and spontaneous fasting, acclimation to cold and acclimation to natural winter conditions) are reviewed. The hypothesis of the PS role in synchronising and endogenous "kindling" of the visceral function ultradian rhythms is substantiated. Some new data are presented on entering torpor as a phenomenon of the "dramatic" neuronal plasticity.     

Effects of dihydroergotoxine methane sulphonate (Redergine) on sleep in cats deprived of paradoxical sleep

Dihydroergotoxine methane sulphonate (DHET 1.0 mg/kg i.p.) was administered to cats deprived of paradoxical sleep (PS) for 72 h and 23 h of recovery sleep were recorded. During the first 12 h of recovery sleep slow-wave sleep (SWS) was significantly increased. There were no significant changes in the amounts of wakefulness (W), PS and several sleep indices. Analysis of the entire 23 h of recording period revealed no significant changes in any of the parameters studied. The results suggest that DHET has SWS enhancing property in the condition where "pressure" for PS was increased.     

Regional organisation of brain activity during paradoxical sleep (PS)

Human brain function is regionally organised during paradoxical sleep (PS) in a very different way than during wakefulness or slow wave sleep. The important activity in the pons and in the limbic/paralimbic areas constitutes the key feature of the functional neuroanatomy of PS, together with a relative quiescence of prefrontal and parietal associative cortices. Two questions are still outstanding. What neurocognitive and neurophysiological mechanisms may explain this original organization of brain function during PS? How the pattern of regional brain function may relate to dream content? Although some clues are already available, the experimental answer to both questions is still pending.     

Possible mechanism of cannabinoid-mediated modulation of signal transduction through the basal ganglia

A possible mechanism of cannabinoid-mediated akinesia is suggested. This effect is proposed to be the consequence of a decrease in LTD/LTP in cortical inputs to striatopallidal/striatonigral cells in the matrix due to CB1 receptor activation. In addition, cannabinoids can attenuate locomotor activity due to a reducing of glutamate/GABA release from axon terminals of subthalamic nucleus/striatonigral cells of matrix and subsequent decrease/increase in the activity of neurons of globus pallidus/substantia nigra pars reticulata. Cannabinoid-mediated rise of dopamine release might be a result of a decrease of dopamine neuron inhibition by striatonigral cells of striosomes. It follows from the suggested mechanism that an inactivation (activation) of CB1 receptors leading to rise (lowering) of the motor activity can be useful for treatment of Parkinson (Huntington) disease.     

Role of the lateral paragigantocellular nucleus in the network of paradoxical (REM) sleep: an electrophysiological and anatomical study in the rat

The lateral paragigantocellular nucleus (LPGi) is located in the ventrolateral medulla and is known as a sympathoexcitatory area involved in the control of blood pressure. In recent experiments, we showed that the LPGi contains a large number of neurons activated during PS hypersomnia following a selective deprivation. Among these neurons, more than two-thirds are GABAergic and more than one fourth send efferent fibers to the wake-active locus coeruleus nucleus. To get more insight into the role of the LPGi in PS regulation, we combined an electrophysiological and anatomical approach in the rat, using extracellular recordings in the head-restrained model and injections of tracers followed by the immunohistochemical detection of Fos in control, PS-deprived and PS-recovery animals. With the head-restrained preparation, we showed that the LPGi contains neurons specifically active during PS (PS-On neurons), neurons inactive during PS (PS-Off neurons) and neurons indifferent to the sleep-waking cycle. After injection of CTb in the facial nucleus, the neurons of which are hyperpolarized during PS, the largest population of Fos/CTb neurons visualized in the medulla in the PS-recovery condition was observed in the LPGi. After injection of CTb in the LPGi itself and PS-recovery, the nucleus containing the highest number of Fos/CTb neurons, moreover bilaterally, was the sublaterodorsal nucleus (SLD). The SLD is known as the pontine executive PS area and triggers PS through glutamatergic neurons. We propose that, during PS, the LPGi is strongly excited by the SLD and hyperpolarizes the motoneurons of the facial nucleus in addition to local and locus coeruleus PS-Off neurons, and by this means contributes to PS genesis.     

Dopamine-glutamate interactions in the basal ganglia

Summary In an attempt to formulate a working hypothesis of basal-ganglia functions, arguments are considered suggesting that the basal ganglia are involved in a process of response selection i.e. in the facilitation of wanted and in the suppression of unwanted behaviour. The meso-accumbal dopamine-system is considered to mediate natural and drug-induced reward and sensitization. The meso-striatal dopamine-system seems to fulfill similar funcions: It may mediate reinforcement which strengthens a given behaviour when elicited subsequently, but which is not experienced as reward or hedonia.Glutamate as the transmitter of the corticofugal projections to the basal ganglia nuclei and of the subthalamic neurons is critically involved in basal ganglia funcions and dysfunctions; for example Parkinson's disease can be considered to be a secondary hyperglutamatergic disease. Additionally, glutamate is an essential factor in the plasticity response of the basal-ganglia. However, opposite to previous suggestions, the NMDA-receptor blocker MK-801 does not prevent psychostimulant- nor morphine-induced day to day increase (sensitization) of locomotion. Also the day to day increase of haloperidol-induced catalepsy was not prevented by MK-801.     

Self-deprivation of paradoxical sleep in cats

The phenomenon of paradoxical sleep (PS) self-deprivation has been detected and described. The self-deprivation is acquired just as a classical conditioned reflex during enforced PS deprivation both by water tank procedure and by the animal's awakenings in response to sensory stimuli or direct electric stimulation of activating structures of the midbrain and diencephalon, following the transition of slow-wave sleep to PS. In this situation the transition of the brain from one physiological state to another is a conditioned signal, and sensory stimulation or brain stimulation, resulting in arousal reaction, serves as an unconditioned stimulus. It is suggested that the detection and analysis of PS self-deprivation are of a great importance, on the one hand, for correct understanding of the functional significance of this physiological brain state, and, on the other hand, for accurate analysis and assessment of the dissociative processes, observed during PS deprivation and postdeprivation period.     

Motor functions of the basal ganglia

This session dealt with the structure and function of the basal ganglia and their role in motor control. The key issues discussed in the first four presentations concerned the pathophysiology of movement performance in parkinsonian patients and in animal models of this disease. Three papers were presented on neurochemically specified subsystems of the basal ganglia. Therapeutic aspects (stereoencephalotomy and chronic electrical stimulation of neural tissue) were discussed in the last two papers. A brief account is given on the highlights of each of these reports.     

PET imaging of the basal ganglia

The present chapter reviews PET imaging in basal ganglia disorders; Parkinson's disease is used as a model of these disorders because the neurochemical pathobiology of this disease is well known and great advances in the imaging area have been achieved. Other basal ganglia disorders including Tourette's syndrome, dystonia, Huntington's chorea and Wilson's disease are also dealt with. With PET and SPECT techniques, the whole integrative dopaminergic network of neurons can be studied, which plays an important role in differential diagnostics. Furthermore, pharmacological effects of medication can be visualized and the role of stereotaxic neurosurgery can be evaluated. Finally, functional imaging gives clues about the prognosis and rehabilitation aspects of the basal ganglia disorders.