Aging effects on spatial tuning of hippocampal place cells in mice

One reason the electrophysiological correlates of hippocampal neurons are of interest is the possibility that they reflect their representational properties, presumably spatial/relational ones. Stable spatial representations, based on activity of ensembles of hippocampal place cells, initially develop through a series of short-episodic spatial tunings. Hence these short-episodic spatial tunings are important for understanding the establishment of stable place fields. Studies of age-related changes in place cell activities traditionally focus on place fields. In the present study, we characterized the short-episodic spatial tunings (1-min bins) of hippocampal CA1 place cells of freely moving mice in a familiar cylinder arena, and compared these functions in young and old mice. Spatial tuning was expressed by spatial selectivity, which we found fluctuated across a 16-min recording session in both young and old mice. High spatial selectivity, which is mainly due to the low firing of a place cell out of the place field in young mice, was significantly higher in old mice. The high firing rate out of the place field was the main factor contributing to significantly lower spatial selectivity in old mice. In addition, young mice showed a broad peak in the spatial selectivity between 4 and 10 min. In contrast old mice showed no peak in the spatial selectivity during this time period. The stability of place fields after a 24-h interval was also lower in old mice than in young mice. The low spatial tuning and unstable place fields suggest that a hippocampal-based spatial representation was impaired in the old mice. Furthermore, we speculate that the age-related impairment in hippocampal inhibition system may be involved in the impaired spatial representation of hippocampal CA1 place cells in old mice. Electronic Publication     

帕金森病相关基因的模糊聚类分析

目的通过分析与帕金森病相关基因之间的相互关系，探讨遗传因素对帕金森病发病机制的影响，为帕金森病的预防及临床诊断和治疗提供可能的遗传学参考依据。方法分别对NCBI中Genbank数据库中的与帕金森病相关基因序列进行两两序列的局部比对分析。确定相关序列的度量关系，并采用模糊聚类的方法进行聚类分析。结果由模糊聚类的结果可知，当α=0．6时，共分为三类，其分别为：{x2，x12,x9，x17，x3，x7，x10,x13，x14,x18,x19}；{x5,x16，x1，x6}；{x4，x8，x11,x15}。结论由聚类分析的角度可推断：被聚为一类的基因其功能普遍具有相似性。     

Seeing or not seeing where your hands are

Previous findings have demonstrated the existence of a visual peripersonal space centered on the hand in humans and its modulatory effects on tactile perception. A strong modulatory effect of vision on touch perception was found when a visual stimulus was presented near the hand. In contrast, when the visual stimulus was presented far from the hand, only a weak modulatory effect was found. The aim of the present study was to verify whether such cross-modal links between touch and vision in the peripersonal space centered on the hand could be mediated by proprioceptive signals specifying the current hand positions or if they directly reflect an interaction between two sensory modalities, i.e., vision and touch. To this aim, cross-modal effects were studied in two different experiments: one in which patients could see their hands and one in which vision of their hands was prevented. The results showed strong modulatory effects of vision on touch perception when the visual stimulus was presented near the seen hand and only mild effects when the vision of the hand was prevented. These findings are explained by referring to the activity of bimodal neurons in premotor and parietal cortex of macaque, which have tactile receptive fields on the hand, and corresponding visual receptive fields in the space immediately adjacent to the tactile fields. One important feature of these bimodal neurons is that their responsiveness to visual stimuli delivered near the body part is reduced or even extinguished when the view of the body part is prevented. This implies that, at least for the hand, the vision of the hand is crucial for determining the spatial mapping between vision and touch that takes place in the peripersonal space. In contrast, the proprioceptive signals specifying the current hand position in space do not seem to be relevant in determining the cross-modal interaction between vision and touch.     

Decline in visual attention and spatial memory in aged rats

The present study was a longitudinal study of age-related changes in performance of the 5-choice serial reaction time task, a test of visual attention. Following acquisition of the task, animals were tested on two occasions on their ability to perform the 5-choice task. In Test 1 (Young: 7 months; Aged: 13–14 months) no age-related effects on baseline performance were revealed. However, increasing the attentional load of the task revealed an impairment in choice accuracy by animals of the Aged group. In Test 2 (Young: 10–11 months; Aged 23–24 months), animals of the Aged group were significantly impaired on the baseline schedule of the task compared to the Young group. The deficit in accuracy on the task could be improved in the Aged animals by decreasing the attentional load. The results of the present study suggest a deficit in attentional function as a result of the aging process, markedly similar to that observed following lesions of the basalo-cortical cholinergic system.     

Compensatory eye movements in the presence of conflicting canal and otolith signals

Summary Orbital motion of the head with the face directed towards the axis of rotation is a stimulus to the otolith organs which is in the opposite rightwards-leftwards sense to the rotational stimulus to the semicircular canals. This can be experienced, for example, by a child held at arms length en face and swung from side to side. As one swings, say to the right, the child's head rotates to its right yet moves linearly to its left. Eye movement responses to a transient orbital movement were observed whilst subjects fixated earth-fixed targets, i) a near target placed between the head and the axis whose relative displacement is in the same direction as head rotation, and ii) a far target placed beyond the axis whose relative motion is in the opposite direction to head rotation. The motion stimuli evoked slow phase eye movements at 45 ms latency, always in the opposite direction to head rotation, thus compensating for the motion of the far target but in the wrong direction for fixating the near target. Theoretically, fixating the near target demands a predominance of the otolith ocularreflex, which would give an eye movement in the correct direction. However, despite visual cues, it seems that if the canal and otolith-ocular reflexes are evoked in opposing directions, the otolith reflex fails to operate at a sensitivity sufficiently high to reverse the direction of the canal-reflex.     

Simulation Studies of Latency Measures of Components of the Event-Related Brain Potential

We compared the accuracy of P300 latency estimates obtained with different procedures under several simulated signal and noise conditions. Both preparatory and signal detection techniques were used. Preparatory techniques included frequency filters and spatial filters (single electrode selection and Vector filter). Signal detection techniques included peak-picking, cross-correlation, and Woody filter. Accuracy in the latency estimation increased exponentially as a function of the signal-to-noise ratio. Both Woody filter and cross-correlation provided better estimates than peak-picking, although this advantage was reduced by frequency filtering. For all signal detection techniques, Vector filter provided better estimates than single electrode selection. Large component overlap impaired the accuracy of the estimates obtained with both single electrode selection and Vector filter, but with Vector filter impairment occurred only when the overlapping component had a scalp distribution that was similar to the scalp distribution of the signal component. The effects of varying noise characteristics, P300 duration and latency, and the parameters of Vector filter were also investigated.     

Functional Cluster Analysis of CT Perfusion Maps: A New Tool for Diagnosis of Acute Stroke?

CT perfusion imaging constitutes an important contribution to the early diagnosis of acute stroke. Cerebral blood flow (CBF), cerebral blood volume (CBV) and time-to-peak (TTP) maps are used to estimate the severity of cerebral damage after acute ischemia. We introduce functional cluster analysis as a new tool to evaluate CT perfusion in order to identify normal brain, ischemic tissue and large vessels. CBF, CBV and TTP maps represent the basis for cluster analysis applying a partitioning (k-means) and density-based (density-based spatial clustering of applications with noise, DBSCAN) paradigm. In patients with transient ischemic attack and stroke, cluster analysis identified brain areas with distinct hemodynamic properties (gray and white matter) and segmented territorial ischemia. CBF, CBV and TTP values of each detected cluster were displayed. Our preliminary results indicate that functional cluster analysis of CT perfusion maps may become a helpful tool for the interpretation of perfusion maps and provide a rapid means for the segmentation of ischemic tissue.     

Control of single-joint movements in deafferented patients: evidence for amplitude coding rather than position control

Two deafferented patients and several control subjects participated in a series of experiments to investigate how accurate single-joint movements are programed, spatially calibrated, and updated in the absence of proprioceptive information. The deafferented patients suffered from a permanent and severe loss of large sensory myelinated fibers below the neck. Subjects performed, with and without vision, sequences of forearm supinations and pronations with two temporal delays between each movement (0 s and 8 s). Overall, the lack of proprioception did not yield any significant decrease in movement accuracy when vision was available. Without vision, the absence of proprioceptive afferents yielded (1) significantly larger spatial errors, (2) amplitude errors similar to those of control subjects, and (3) a significant drift when an 8-s delay was introduced between two successive movements. Subjects also performed, without vision, a 20 supination followed by a 20 pronation that brought back the wrist to the starting position. On some trials, the supination was blocked unexpectedly by way of a magnetic brake. When the supination was blocked, subjects were already on the second target and no pronation was required when the brake was released. The defferented patients, unaware of the procedure, always produced a 20 pronation. These data confirm that deafferented patients were not coding a final position. It rather suggests that they coded an amplitude and translated the spatial distance between the two targets in a corresponding force pulse. Overall, the results highlight the powerful and key role of proprioceptive afferents for calibrating the spatial motor frame of reference.     

Spatial learning and memory following fimbria-fornix transection and grafting of fetal septal neurons to the hippocampus

Summary The ability of intrahippocampal grafts of fetal septal-diagonal band tissue, rich in developing cholinergic neurons, to ameliorate cognitive impairments induced by bilateral fimbria-fornix transections in rats was examined in three experiments using the Morris water-maze to test different aspects of spatial memory. Experiment 1. Rats with fimbria-fornix lesions received either septal cell suspension grafts or solid septal grafts; normal rats and rats with lesions alone were used as controls. Sixteen weeks after surgery, the rats' spatial learning and memory were tested in the water-maze using a place test, designed to investigate place navigation performance, in which rats learned to escape from the water by swimming to a platform hidden beneath the water's surface. After 5 days of training, the rats were given a spatial probe test in which the platform was removed from the tank to test spatial reference memory. Experiment 2. The same rats used in Exp. 1 were tested in a delayed-match-to-sample, working memory version of the water-maze task. The platform was located in one of two possible locations during each trial, which was composed of 2 swims. If the rat remembered the location of the platform on the 2nd swim of a trial, it should find the platform more quickly on that swim, and thereby demonstrate working memory. Experiment 3. Prior to receiving fimbria-fornix lesions, normal rats were trained in a modification of the water-maze task using alternating cue navigation and place navigation trials (i.e., with visible or non-visible escape platforms). The retention and reacquisition of the place task and the spatial probe test were examined in repeated tests up to 6 months after the lesion and intrahippocampal grafting of septal cell suspensions. The effects of central muscarinic cholinergic receptor blockade with atropine were also tested. Normal rats performed well in both the place and spatial probe tests. In contrast, rats with fimbria-fornix lesions only were unable to acquire or retain spatial information in any test. Instead, these rats adopted a random, nonspatial search strategy, whereby their latencies to find the platform decreased in the place navigation tasks. Sixty to 80% of the rats with septal suspension or solid grafts had recovered place navigation, i.e., the ability to locate the platform site in the tank, in Exp. 1 and 3, and they showed a significantly improved performance in the working memory test in Exp. 2. Atropine abolished the recovered place navigation in the grafted rats, whereas normal rats were impaired to a lesser extent. In contrast, atropine had no effect on the non-spatial strategy adopted by rats with fimbria-fornix lesions only. The results show that: (1) fimbria-fornix lesions disrupt spatial learning and memory in both naive and pretrained rats; (2) with extended training the fimbria-fornix lesioned rats develop an efficient non-spatial strategy, which enables them to reduce their escape latency to levels close to those of intact controls; (3) intrahippocampal septal grafts can restore the ability of the lesioned rats to use spatial cues in the localization of the platform site; and (4) the behavioural recovery produced by grafts is dependent upon an atropine sensitive mechanism.     

The effect of transcranial magnetic stimulation on the latencies of vertical saccades

In this study, we investigated the effect of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) on the latency of two different types of visually-guided vertical saccades: reflexive saccades triggered by the sudden onset of a target, and saccades towards target locations known in advance. For this reason, we used two oculomotor tasks: a gap and a delay task, respectively. Nine normal subjects performed vertical saccades at ±7.5 and ±15°. TMS was applied at 80 and 100 ms after target onset in the gap task, and after fixation offset in the delay task. Without TMS, we confirmed a latency asymmetry in the gap task favouring upward saccades at the lower eccentricity (7.5°), and a latency symmetry in the delay task. TMS increased the latencies of all saccades in the delay task, when delivered at 100 ms. This effect was mostly pronounced for downward saccades at 7.5°. As a result, saccade latencies showed an asymmetry in this condition, similar to the one observed in the gap task without TMS. The gap task with TMS resulted in a variable latency distribution and no significant overall effect on saccade latency. Our results indicate that the right PPC is involved in the initiation of vertical saccades in the delay task, and that this involvement appears to be enhanced for downward saccades. A conclusion for the involvement of this area in the gap task could not be drawn from this study.