Brain Research Reviews最新文献

Crucial to our everyday social functioning is an ability to interpret the behaviors of others. This process involves a rapid understanding of what a given action is not only in a physical sense (e.g., a precision grip around the stem of a wine glass) but also in a semantic sense (e.g., an invitation to “cheers”). The functional properties of fronto-parietal mirror neurons (MNs), which respond to both observed and executed actions, have been a topic of much debate in the cognitive neuroscience literature. The controversy surrounds the role of the “mirror neuron system” in action understanding: do MNs allow us to comprehend others' actions by allowing us to internally represent their behaviors or do they simply activate a direct motor representation of the perceived act without recourse to its meaning? This review outlines evidence from both human and primate literatures, indicating the importance of end-goals in action representations within the motor system and their predominance in influencing action plans. We integrate this evidence with recent views regarding the complex and dynamic nature of the mirror neuron system and its ability to respond to broad motor outcomes.

Digital reconstruction of neuronal morphology is a powerful technique for investigating the nervous system. This process consists of tracing the axonal and dendritic arbors of neurons imaged by optical microscopy into a geometrical format suitable for quantitative analysis and computational modeling. Algorithmic automation of neuronal tracing promises to increase the speed, accuracy, and reproducibility of morphological reconstructions. Together with recent breakthroughs in cellular imaging and accelerating progress in optical microscopy, automated reconstruction of neuronal morphology will play a central role in the development of high throughput screening and the acquisition of connectomic data. Yet, despite continuous advances in image processing algorithms, to date manual tracing remains the overwhelming choice for digitizing neuronal morphology. We summarize the issues involved in automated reconstruction, overview the available techniques, and provide a realistic assessment of future perspectives.

Although the central noradrenergic system has been shown to be involved in a number of behavioral and neurophysiological processes, the relation of these to its role in depressive illness has been difficult to define. The present review discusses the hypothesis that one of its chief functions that may be related to affective illness is the inhibition of behavioral activation, a prominent symptom of the disorder. This hypothesis is found to be consistent with most previous neuropsychopharmacological and immunohistochemical experiments on active behavior in rodents in a variety of experimental conditions using manipulation of neurotransmission at both locus coeruleus and forebrain adrenergic receptors. The findings support a mechanism in which high rates of noradrenergic neural activity suppress the neural activity of principal neurons in forebrain regions mediating active behavior. The suppression may be mediated through postsynaptic galaninergic and adrenergic receptors, and via the release of corticotrophin-releasing hormone. The hypothesis is consistent with clinical evidence for central noradrenergic system hyperactivity in depressives and with the view that this hyperactivity is a contributing etiological factor in the disorder. A similar mechanism may underlie the ability of the noradrenergic system to suppress seizure activity suggesting that inhibition of the spread of neural activation may be a unifying function.

Adult rodents picked up by the tail and slowly descending towards a horizontal surface extend all four limbs in anticipation of contact. Mouse mutants with pathologies in various brain regions and the spinal cord display instead a flexion response, often characterized by paw-clasping and a bat-like posture. These phenotypes are observed in mice with lesions in cerebellum, basal ganglia, and neocortex, as well as transgenic models of Alzheimer's disease. The underlying mechanism appears to include cerebello-cortico-reticular and cortico-striato-pallido-reticular pathways, possibly triggered by changes in noradrenaline and serotonin transmission.

The Camillo Golgi's school of Histology and General Pathology in Pavia played an important role in the development of medical-biological studies in Italy in the period after Unification of the state. Founded around 1880 when Golgi (1843–1926) began to wield power at the University of Pavia, the school soon became famous for the distinctive morphological basis of its studies. Many of its staff members made important discoveries and won international acclaim. The school however went into decline after 1910 because of its rigid adherence to the morphological approach that had characterized its golden years at a time when the international scientific world was developing other fundamental methodological criteria for medical–biological studies.

Neurite outgrowth is a fundamental process in the differentiation of neurons. The first, seminal study documenting the generation of “appendages” (now known as filopodia and lamellipodia) on the “cones d'accroissement,” the specialized growth cones at the tips of neurites, was reported by Cajal still in the XIXth century, investigating chicken neurons embryos stained by the Golgi's reazione nera. Since then, studies have continued using, in addition to brain tissues, powerful in vitro models, i.e. primary cultures of pyramidal neurons from the hippocampus and neurosecretory cell lines, in particular PC12 cells. These studies have documented that neuronal neurites, upon sprouting from the cell body, give rise to both axons and dendrites. The specificity of these differentiated neurites depends on the diffusion barrier established at the initial segment of the axon and on the specialized domains, spines and presynaptic boutons, assembled around complexes of scaffold proteins. The two main, coordinate mechanisms that support neurite outgrowth are (a) the rearrangement of the cytoskeleton and (b) the expansion of the plasma membrane due to the exo/endocytosis of specific vesicles, distinct from those filled with neurotransmitters (clear and dense-core vesicles). The latter process is the main task of this review. In axons the surface-expanding exocytoses are concentrated at the growth cones; in dendrites they may be more distributed along the shaft. At least two types of exocytic vesicles appear to be involved, the enlargeosomes, positive for VAMP4, during early phases of development, and Ti-VAMP-positive vesicles later on. Outgrowth studies, that are now intensely pursued, have already yielded results of great importance in brain cell biology and function, and are playing an increasing role in pathology and medicine.

Since the discoveries of Camillo Golgi and Ramón y Cajal, the precise cellular organization of the cerebellum has inspired major computational theories, which have then influenced the scientific thought not only on the cerebellar function but also on the brain as a whole. However, six major issues revealing a discrepancy between morphologically inspired hypothesis and function have emerged. (1) The cerebellar granular layer does not simply operate a simple combinatorial decorrelation of the inputs but performs more complex non-linear spatio-temporal transformations and is endowed with synaptic plasticity. (2) Transmission along the ascending axon and parallel fibers does not lead to beam formation but rather to vertical columns of activation. (3) The olivo-cerebellar loop could perform complex timing operations rather than error detection and teaching. (4) Purkinje cell firing dynamics are much more complex than for a linear integrator and include pacemaking, burst–pause discharges, and bistable states in response to mossy and climbing fiber synaptic inputs. (5) Long-term synaptic plasticity is far more complex than traditional parallel fiber LTD and involves also other cerebellar synapses. (6) Oscillation and resonance could set up coherent cycles of activity designing a functional geometry that goes far beyond pre-wired anatomical circuits. These observations clearly show that structure is not sufficient to explain function and that a precise knowledge on dynamics is critical to understand how the cerebellar circuit operates.

Giuseppe Moruzzi was born one century ago; he was an outstanding Italian neurophysiologist, who was particularly famous for his contributions to the study of the mechanisms underlying the control of the sleep–waking cycle in mammals. In 1990, Rita Levi-Montalcini, Moruzzi's great friend and admirer, used the occasion of an invitation by the University of Parma, where Moruzzi graduated in medicine in 1933, to celebrate Moruzzi's scientific achievements. She wished to pay a tribute to Moruzzi's human and ethical qualities by portraying him as a “perfect model” for the young generation wishing to pursue scientific research. The transcription of “Rita's” tribute to Moruzzi links two of the greatest figures of Italian neuroscience and also provides a lively account of how the personal histories of two promising young scientists intertwined with the great and tragic events of world history in the past century.

The black reaction allowed Golgi to describe with amazing detail the morphology of glial cells as well as their proximal location and intimate connections with neurons and blood vessels. Based on this location, Golgi hypothesized that glial cells were functional units in the nervous system and were not merely a structural support medium. Relatively recent advances have confirmed the importance of glial cells in nervous system function and disease. The occurrence of gliosis is considered the hallmark of damaged tissue. Gliosis can differentially influence disease development and it is a prevailing characteristic of temporal lobe epilepsy. Its presence in the epileptic hippocampi might contribute to hyperexcitability, the development of aberrant neurogenic changes and inflammatory processes related to seizures. Considering the accumulating data regarding the pathological role of glial cells in epilepsy, novel therapeutic approaches that target glial cells are being explored. Such therapeutic approaches directed to glial cells present a novel perspective for the management of refractory pathologies.

The third paper by Camillo Golgi on his new method was on the olfactory bulb. This paper has never been translated into English, but is of special interest both for its pioneering description of olfactory bulb cells and for containing the first illustration by Golgi of cells stained with his new method. A translation into English is provided in this paper, together with commentaries on the significant points in his descriptions. These results are placed in the perspective of Cajal's subsequent first publication on the olfactory bulb and brief mention of the work of other early histologists. This perspective allows one to see more clearly Golgi's fundamental contributions to the olfactory bulb in particular and to the description of the neuronal architecture of the brain in general.