Automated three-dimensional analysis of histological and autoradiographic rat brain sections: application to an activation study.

Besides the newly developed positron emission tomography scanners (microPET) dedicated to the in vivo functional study of small animals, autoradiography remains the reference technique widely used for functional brain imaging and the gold standard for the validation of in vivo results. The analysis of autoradiographic data is classically achieved in two dimensions (2D) using a section-by-section approach, is often limited to few sections and the delineation of the regions of interest to be analysed is directly performed on autoradiographic sections. In addition, such approach of analysis does not accommodate the possible anatomical shifts linked to dissymmetry associated with the sectioning process. This classic analysis is time-consuming, operator-dependent and can therefore lead to non-objective and non-reproducible results. In this paper, we have developed an automated and generic toolbox for processing of autoradiographic and corresponding histological rat brain sections based on a three-step approach, which involves: (1) an optimized digitization dealing with hundreds of autoradiographic and histological sections; (2) a robust reconstruction of the volumes based on a reliable registration method; and (3) an original 3D-geometry-based approach to analysis of anatomical and functional post-mortem data. The integration of the toolbox under a unified environment (in-house software BrainVISA, http://brainvisa.info) with a graphic interface enabled a robust and operator-independent exploitation of the overall anatomical and functional information. We illustrated the substantial qualitative and quantitative benefits obtained by applying our methodology to an activation study (rats, n=5, under unilateral visual stimulation).     

Inversion of Melatonin Circadian Rhythm in Chronic Alcoholic Patients during Withdrawal: Preliminary Study on Seven Patients

Aims: The inversion of melatonin circadian rhythm secretionin some alcoholics during both intake and acute withdrawal hasbeen widely reported. In the same way, what happens to thisinversion when these patients are in long-term withdrawal isnot known. To document this abnormality in alcoholics afterwithdrawal we investigated melatonin secretion observed duringchronic alcoholization and after withdrawal. Methods: We measuredthe urinary 6-sulfatoxymelatonin (6SM) (6SM/creatinine ratio),main metabolite of the hormone, in two fractions, one diurnaland the other nocturnal, in seven alcohol-dependent patientspresenting with this abnormality during alcoholization at twotimes: in acute withdrawal phase (under benzodiazepines) and15 days after beginning of withdrawal (free of any psychotropictreatment). Results: Our results show that this reversed rhythmof melatonin secretion as seen by the diurnal excretion of 6SM(6SM/creatinine ratio) persists during acute withdrawal in morethan half of the patients and is still present 15 days afterwithdrawal in three patients. Conclusion: It is remarkable thatthe inversion of the melatonin rhythms gets corrected in fourout of seven patients after withdrawal. But, the circadian disorganizationof melatonin secretion in three patients could underline a desynchronizationin some alcoholic patients and may indicate more widespreadcircadian temporal structure disturbances in these patients.     

Fatigue and fitness modelled from the effects of training on performance

Summary The purpose of this study was to compare two ways of estimating both fatigue and fitness indicators from systems model of the effects of training on performance. The model was applied to data concerning the training of a hammer thrower. The variations in performance were mathematically related to the successive amounts of training. The model equation was composed of negative (NF) and positive (PF) functions. The NF and PF were associated with the fatigue and fitness estimated in previous studies. Using another method, fatigue and fitness indicators were estimated from a combination of NF and PF. The influence of training on performance was negatively associated with fatigue (NI), and positively to fitness (PI). The changes in performance were well described by the model in the present study (r = 0.96,N = 19,P<0.001). Significant correlations were observed between NF and NI (r = 0.93,P < 0.001) on the one hand and between PF and PI (r = 0.90,P < 0.001) on the other. The absolute values and the time variations of PI and NI were closer to the change in performance than NF and PF. The NF and PF were accounted for mainly by the accumulation of amounts of training. On the other hand, NI and PI were accounted for rather by the impact of these amounts of training on performance.     

Pathology of inverted Takotsubo cardiomyopathy

Myocardial dysfunction without coronary involvement may occur in acute cerebral diseases. The inverted Takotsubo pattern has been recently recognized as a novel heart neurologic stress-related syndrome. We report on the case of a 40-year-old woman presenting with massive subarachnoid hemorrhage and brain death. Echocardiography revealed an extensive left ventricular circumferential akinesis except at the apex. Histologic analysis of the heart confirmed the absence of myocardial infarction and revealed only sparse foci of myocyte necrosis with contraction bands in the akinetic areas.     

Anatomical evidence for direct connections between the shell and core subregions of the rat nucleus accumbens

The nucleus accumbens is thought to subserve different aspects of adaptive and emotional behaviors. The anatomical substrates for such actions are multiple, parallel ventral striatopallidal output circuits originating in the nucleus accumbens shell and core subregions. Several indirect ways of interaction between the two subregions and their associated circuitry have been proposed, in particular through striato-pallido-thalamic and dopaminergic pathways. In this study, using anterograde neuroanatomical tracing with Phaseolus vulgaris-leucoagglutinin and biotinylated dextran amine as well as single-cell juxtacellular filling with neurobiotin, we investigated the intra-accumbens distribution of local axon collaterals for the identification of possible direct connections between the shell and core subregions. Our results show widespread intra-accumbens projection patterns, including reciprocal projections between specific parts of the shell and core. However, fibers originating in the core reach more distant areas of the shell, including the rostral pole (i.e. the calbindin-poor part of the shell anterior to the core) and striatal parts of the olfactory tubercle, than those arising in the shell and projecting to the core. The latter projections are more restricted to the border region between the shell and core. The density of the fiber labeling within both the shell and core was very similar. Moreover, specific intrinsic projections within shell and core were identified, including a relatively strong projection from the rostral pole to the rostral shell, reciprocal projections between the rostral and caudal shell, as well as projections within the core that have a caudal-to-rostral predominance. The results of the juxtacellular filling experiments show that medium-sized spiny projection neurons and medium-sized aspiny neurons (most likely fast-spiking) contribute to these intra-accumbens projections. While such neurons are GABAergic, the intrastriatal projection patterns indicate the existence of lateral inhibitory interactions within, as well as between, shell and core subregions of the nucleus accumbens.     

Behavioral Profiles of Genetically Selected Aggressive and Nonaggressive Male Wild House Mice in Two Anxiety Tests

Artificially selected aggressive (SAL) and non-aggressive (LAL) male house mice were tested in a hexagonal tunnel maze and light-dark preference (LD) box to determine if the bidirectional selection for aggressive behavior leads to a coselection for different levels of trait anxiety. The tunnel maze consists of an open, brightly lit central arena surrounded by a complex system of interconnecting tunnels. As in the LD box, animals which spend less time and are less active in the brightly illuminated section of the maze are considered to have higher anxiety levels. In the tunnel maze, the LAL mice showed more exploration and spent more time in the central arena than the SAL animals, but only during the final 2 min of the 6-min test. This reduced preference for the central arena was not due to general inactivity or a failure of the SAL to find the central arena and indicates a higher level of state anxiety in the aggressive animals. In contrast, no anxiety-like differences were found in the LD box, either for the percentage of time spent in the light compartment or for the number of crossings. SAL males actually showed higher levels of moving and rearing, and lower levels of freezing, than did LAL males.