What are the computations of the cerebellum,the basal ganglia and the cerebral cortex?

The classical notion that the cerebellum and the basal ganglia are dedicated to motor control is under dispute given increasing evidence of their involvement in non-motor functions. Is it then impossible to characterize the functions of the cerebellum, the basal ganglia and the cerebral cortex in a simplistic manner? This paper presents a novel view that their computational roles can be characterized not by asking what are the “goals” of their computation, such as motor or sensory, but by asking what are the “methods” of their computation, specifically, their learning algorithms. There is currently enough anatomical, physiological, and theoretical evidence to support the hypotheses that the cerebellum is a specialized organism for supervised learning, the basal ganglia are for reinforcement learning, and the cerebral cortex is for unsupervised learning.This paper investigates how the learning modules specialized for these three kinds of learning can be assembled into goal-oriented behaving systems. In general, supervised learning modules in the cerebellum can be utilized as “internal models” of the environment. Reinforcement learning modules in the basal ganglia enable action selection by an “evaluation” of environmental states. Unsupervised learning modules in the cerebral cortex can provide statistically efficient representation of the states of the environment and the behaving system. Two basic action selection architectures are shown, namely, reactive action selection and predictive action selection. They can be implemented within the anatomical constraint of the network linking these structures. Furthermore, the use of the cerebellar supervised learning modules for state estimation, behavioral simulation, and encapsulation of learned skill is considered. Finally, the usefulness of such theoretical frameworks in interpreting brain imaging data is demonstrated in the paradigm of procedural learning.     

Does the intergeniculate leaflet play a role in the integration of the photoperiod by the suprachiasmatic nucleus?

The circadian clock located in the suprachiasmatic nuclei (SCN) is influenced by the photoperiod. After the transfer from a long (LP 14:10) to a short photoperiod (SP 10:14), the adjustment of the light sensitivity of the SCN, in terms of Fos expression, takes 25 nights. To examine the contribution of the thalamic intergeniculate leaflet (IGL) and its NPY-immunoreactive projection in the extension of the duration of the photosensitive phase of the SCN, male Syrian hamsters received electrolytic lesions of the IGL. We showed a lower number of Fos-ir cells in the SCN of IGLx hamsters following a light pulse applied 13 h after dark onset, 25 nights after the transfer from LP to SP compared to sham operated hamsters. The present study shows that the integrity of the IGL is necessary to have a complete integration of photoperiodic changes by the SCN. This demonstrates the involvement of the IGL in the integration of photoperiodic information by the SCN.     

Modeling the Protonation States of the Catalytic Aspartates in β-Secretase and the Process of the Enzymatic Hydrolysis

背景：阿尔茨海默病(AD）主要表现为脑内β-淀粉样蛋白（Aβ）沉积，Aβ由β-淀粉酶（β- Secretase，BACE）催化水解淀粉样前体蛋白（amyloid precursor protein, APP）产生，但是BACE的催化机制至今仍不清楚。 目的：确定质子在BACE催化性氨基酸(Asp 32 和 Asp 228)中的精确定位，同时在计算机上模拟BACE催化底物APP蛋白的全部过程，揭示BACE催化水解底物的机制。 设计，时间和 SETTING: 全部的量子化学计算在中山大学中山医学院人体解剖教研室进行，2008年8月至2009年3月。 材料: 一台linux计算机工作站，商业性的大型药物设计软件包Schrodinger, 针对学术机构免费的量子化学软件 MOPAC 2007。 方法: 在计算机上构建了一个BACE催化模型，应用量子化学/分子力学(QM/MM)相结合的方法在密度泛函理论水平的基础上计算质子在BACE催化性氨基酸(Asp 32 和 Asp 228)中的精确定位； 在量子化学的半经验理论水平基础上模拟BACE催化水解底物肽EVNL/AAEF的全部过程。 主要结果指标: 计算BACE和底物在不同的单质子化状态下两个催化性氨基酸中的4个羧基氧原子的共面性；在模拟催化水解底物过程中检测BACE催化活性区域内空间和能量的变化。 结果： BACE的同分异构体228o,其4个催化氨基酸羧基氧原子形成的二面角为8.7°；而且利用这种同分异构体（228o）作为初始状态，催化水解底物的活化能最低（1.6959 kcal/mol），焓最高（-7.4055 kcal/mol）。 结论：在催化前，质子最有可能位于BACE的催化氨基酸Asp 228的外位羧基氧原子上,催化水解时，Asp 228作为催化酸，Asp 32 作为催化碱驱动催化水分子攻击底物，形成四面体中间物后，质子的换位到Asp 32的内位羧基氧原子上。     

What is the role of the cerebellum in the pathophysiology of dystonia?

Journal of Neurology -     

Mapping the amphetamine-evoked dopamine release in the brain of the Göttingen minipig

The availability of dopamine D(2/3) binding sites in brain of six male and six female G?ttingen minipigs was measured in a baseline condition and after challenge with amphetamine sulfate (1mg/kg, i.v.) in PET studies with [(11)C]raclopride. Maps of the binding potential (pB; B(max)/K(d)) of [(11)C]raclopride were spatially normalized and co-registered to a common stereotaxic coordinate system for pig brain. The pB maps were then analyzed by volume of interest and voxel-wise comparisons of gender and condition. The mean baseline pB tended to be 10-20% higher in striatum of the female group, but this gender difference was not significant. Variance of the mean baseline pB was higher in the males (44%) than in females (30%), but there was no correlation between pB and individual plasma cortisol or testosterone concentrations. Using statistical parametric mapping, we detected a focus in the right posterior putamen where the magnitude of the amphetamine-evoked decrease in pB was greater in the male than in the female group. Thus, the spatial pattern of reactivity of dopamine D(2/3) receptor availability to amphetamine challenge is not identical in male and female pigs. Within the entire population, the decline in pB evoked by amphetamine (Delta pB) was greater in the ventral striatum (-28%) than in the caudate nucleus (-17%), consistent with earlier reports in monkeys and humans. The magnitude of Delta pB correlated highly with the baseline pB values in all divisions of the striatum. Based upon the principles of competitive binding, the slope of this empirical relationship, f(i), is equal to the fraction of [(11)C]raclopride binding sites sensitive to endogenous dopamine; the magnitude of this fraction ranged from 0.29 in the caudate to 0.36 in the ventral striatum.     

ECT anesthesia: the lighter the better?

BACKGROUND: Electroconvulsive therapy (ECT) is a most effective treatment for patients with major affective disorders. The influence of anesthetic drugs on seizure "adequacy" or on treatment success has not been systematically investigated. METHODS: A bispectral EEG index score (BIS) was used to identify the depth of anesthesia during ECT. Our study included 22 major depressive episode (MDE) patients expanding to 219 ECTs (05/05-01/06) with no limitations of concurrent medication. RESULTS: Fourteen out of the 22 patients showed full remission. Individual number of ECT sessions needed to reach full remission correlated negatively with mean pre-ECT BIS values (p=0.001). Additionally, using a repeated measurement regression analysis significant correlations were found for pre-ECT BIS versus motor response time, seizure concordance, ictal coherence and peak heart rate. CONCLUSION: The results of our study suggest BIS-levels as a predictor of faster ECT response. Controlling BIS-levels before stimulation may have an additional effect on treatment success.     

Why didn't the glia cross the road?

To cross or not to cross the midline? This is the question that pathfinding axons in the developing CNS must answer. In the past few years the molecular mechanisms involved in this decision process have been determined for neurones. A recent paper now shows that glia are also affected by these same mechanisms and that the presence of glia can tip the balance in favour of repulsion or attraction of neurones to the midline.     

What is the origin of the premotor potential recorded from the second lumbrical?

When recording with a palm electrode, a premotor potential (PMP) precedes the compound muscle action potential that is evoked from the second lumbrical muscle following median nerve stimulation. The origin of this PMP has been uncertain. We demonstrate that median sensory nerve action potentials (SNAPs) can be recorded orthodromically with the palm electrode and conclude that the origin of the PMP is a median SNAP arising from antidromically activated digital sensory branches.     

Does the definition of borders of the planum temporale influence the results in schizophrenia?

OBJECTIVE: The planum temporale, a highly asymmetric neocortical area of the temporal lobe, has a possible role in schizophrenia. The authors used three different anatomical definitions of the planum temporale to examine the anterior, posterior, and total planum temporale gray matter volumes simultaneously. METHOD: Magnetic resonance imaging was used to examine 30 male schizophrenic patients and 30 healthy male comparison subjects. The total planum temporale was identical in all three anatomical definitions applied to determine the border between the anterior and posterior planum temporale regions. RESULTS: No significant differences between men with and without schizophrenia were detected with regard to planum temporale volumes and asymmetry coefficients for any of the three definitions. CONCLUSIONS: The authors could not prove the hypothesis that the definition of planum temporale borders influences the results concerning possible disturbances of planum temporale asymmetry in patients with schizophrenia.     

Glutamatergic pathways from the Kölliker-Fuse nucleus to the phrenic nucleus in the rat

After ipsilateral injections of biotinylated dextran amine (BDA) into the K?lliker-Fuse (KF) nucleus and cholera toxin B subunit (CTb) into the ventral horn in C4 to C5 segments of the spinal cord, an overlapping distribution of BDA-labeled axon terminals and CTb-labeled neurons was found in the rostral ventral respiratory group (rVRG) region ipsilateral to the injection sites. After ipsilateral injections of BDA into the KF and Fluoro-Gold (FG) into the ventral horn in C4 to C5 segments of the spinal cord, BDA-labeled axons were found to make asymmetrical synapses with the somata and dendrites of FG-labeled neurons within the neuropil of the rVRG region. Using retrograde tracing combined with immunohistochemistry for phosphate-activated glutaminase (PAG), we observed that as many as 72% of the rVRG neurons projecting to the PhN were immunoreactive for PAG and that approximately 62% and 75% of the KF neurons projecting respectively to the rVRG region and PhN contain PAG immunoreactivity. Using anterograde tracing combined with immunohistochemistry for vesicular glutamate transporter 2 (VGluT2), we further demonstrated that the KF axon terminals in the rVRG and PhN regions as well as the rVRG axon terminals in the PhN region contain VGluT2 immunoreactivity. The present results suggest that the glutamatergic pathways from the KF to the PhN directly and indirectly via the rVRG region may exist and underlie the inspiratory responses that are elicited by activation of the KF neurons.     

What is the locus of the errorless-learning advantage?

In two experiments involving word-stem completion, an advantage was found for errorless over errorful-learning conditions, for both severely and moderately memory-impaired participants. This advantage did not depend on the implicit/explicit nature of the question asked. Additional tests showed that subsequent recognition of target items was good for both groups, but only in the absence of lures derived from participants' prior errors. Source-memory was shown to be virtually absent in the severely impaired group and only weakly present in the moderately impaired group. This combination of results suggests that preserved implicit memory, in the absence of explicit memory, is sufficient for an errorless-learning advantage to accrue.