A Kv1.5 to Kv1.3 switch in endogenous hippocampal microglia and a role in proliferation.
The proliferation of microglia is a normal process in CNS development and in the defense against pathological insults, although, paradoxically, it contributes to several brain diseases. We have examined the types of voltage-activated K(+) currents (Kv) and their roles in microglial proliferation. Microglia were tissue-printed directly from the hippocampal region using brain slices from 5- to 14-d-old rats. Immediately after tissue prints were prepared, unipolar and bipolar microglia expressed a large Kv current, and the cells were not proliferating. Surprisingly, this current was biophysically and pharmacologically distinct from Kv1.3, which has been found in dissociated, cultured microglia, but it was very similar to Kv1.5. After several days in culture the microglia became highly proliferative, and although the Kv prevalence and current density decreased, many cells exhibited a prominent Kv that was indistinguishable from Kv1.3. The Kv1.5-like current was present in nonproliferating cells, whereas proliferating cells expressed the Kv1.3-like current. Immunocytochemical staining showed a dramatic shift in expression and localization of Kv1.3 and Kv1.5 proteins in microglia: Kv1.5 moving away from the surface and Kv1.3 moving to the surface as the cells were cultured. K(+) channel blockers inhibited proliferation, and the pharmacology of this inhibition correlated with the type of Kv current expressed. Our study, which introduces a method for the physiological examination of microglia from identified brain regions, demonstrates the differential expression of two functional Kv subunits and shows that a functional delayed rectifier current is necessary for microglia proliferation. (+info)
Stereoscopic (cyclopean) motion sensing.
This paper reviews literature on the motion processing of dynamic change in binocular disparity, called stereoscopic (cyclopean) motion. Studies investigating the visual processing of stereoscopic motion in the Z-axis, stereoscopic motion in the X/Y plane, and cyclopean motion are discussed. It is concluded that stereoscopic motion is processed by a motion-sensing system composed of special-purpose mechanisms that function like low-level motion sensors. For animals with binocular vision, low-level motion processing may involve, at least in part, stereoscopic processing. (+info)
MT neurons in the macaque exhibited two types of bimodal direction tuning as predicted by a model for visual motion detection.
We previously proposed a model for detecting local image velocity on the magnocellular visual pathway (Kawakami & Okamoto (1996) Vision Research, 36, 117-147). The model detects visual motion in two stages using the hierarchical network that includes component and pattern cells in area MT. To validate the model, we predicted two types of bimodal direction tuning for MT neurons. The first type is characteristic of component cells. The tuning is bimodal when stimulated with high-speed spots, but unimodal for low-speed spots or for bars. The interval between the two peaks widens as the spot's speed increases. The second type is characteristic of pattern cells. The tuning is bimodal when stimulated with low-speed bars, but unimodal for high-speed bars or for spots. The interval widens as the bar's speed decreases. To confirm this prediction, we studied the change of direction tuning curves for moving spots and bars in area MT of macaque monkeys. Out of 35 neurons measured at various speeds, six component cells and four pattern cells revealed the predicted bimodal tunings. This result provided neurophysiological support for the validity of the model. We believe ours is the first systematic study that records the two types of bimodality in MT neurons. (+info)
Testosterone-dependent primer pheromone production in the sebaceous gland of male goat.
To test the hypothesis that the primer pheromone responsible for inducing the "male effect" is produced in the sebaceous gland androgen dependently, we examined the correlation between morphological changes of sebaceous glands and the pheromone activity in skin samples taken from castrated goats that had been treated with testosterone. Five castrated goats were implanted s.c. with testosterone capsules to maintain physiological levels of plasma testosterone for four weeks. Skin samples were obtained from the head region on Day 0 (the day of testosterone implant), Day 7, Day 14, Day 28 (the day of testosterone removal), Day 36, Day 42, and Day 56. Matched blood samples were also collected for measurement of testosterone concentration. The pheromone activity of the ether-extracts of the upper dermal layer containing sebaceous glands was assessed by its stimulatory effect on the hypothalamic GnRH pulse generator, which was monitored for changes of specific multiple unit activity (MUA) in ovariectomized estradiol-primed goats as described previously. The sebaceous gland enlarged during the testosterone treatment but reduced in size after testosterone removal. The pheromone activity first appeared in 2 out of 5 goats on Day 7 and in all the 5 goats by Day 28. Fourteen days after testosterone removal (Day 42), the pheromone activity was no longer detectable in any of the 5 goats. In short, the sebaceous gland size and the pheromone activity shifted almost in parallel. The present results provide strong support for the view that the primer pheromone is produced testosterone dependently in the sebaceous gland of the male goat. (+info)
Ocular microtremor (OMT): a new neurophysiological approach to multiple sclerosis.
Using a piezoelectric transducer, the frequency and pattern of ocular microtremor (OMT) between 50 normal subjects and 50 patients with multiple sclerosis were compared. Controls were age matched. All records were analysed blindly. The frequency of OMT in the normal group was 86 (SD 6) Hz, which was significantly different from that of the multiple sclerosis group (71 (SD) 10 Hz, p<0.001). Those in the multiple sclerosis group with clinical evidence of brain stem or cerebellar disease (n=36) had an average OMT frequency of 67 (SD 9) Hz (p<0.001) compared with normal (n=86), whereas those with no evidence of brain stem or cerebellar involvement (n=14) had a frequency of 81.2 (SD 6) Hz (p<0.05, n=64). The differences between the two multiple sclerosis groups were also significant (p<0. 001, n=50). At least one abnormality (frequency and pattern) of OMT activity was seen in 78% of patients with multiple sclerosis. In the presence of brain stem or cerebellar disease 89% had abnormal records whereas in the absence of such disease 50% had abnormal records. This is the first report of the application of this technique to patients with multiple sclerosis. The results suggest that OMT activity may be of value in the assessment of multiple sclerosis. (+info)
Towards new models of disease and physiology in the neurosciences: the role of induced and naturally occurring mutations.
There is a dearth of good mouse models for central nervous system (CNS) disorders. However, the development of gene-targeted technology and the recognition of the importance of the mouse as a model organism have led to the development of a range of behavioural tests for mice. Spontaneous mutations in mice have already provided important information about the role of novel gene products in disorders such as epilepsy and deafness. This has provided the impetus to the establishment of large-scale mutagenesis programmes to generate new mutations. Tests of sensory and motor function have previously been most frequently used as these are simple to perform and the phenotypes are relatively obvious. Subtle phenotypes, of relevance to pyschiatric disorders such as anxiety and schizophrenia, can be detected using more complex tests. Screens such as prepulse inhibition and startle have been adapted for mice and these can be run with relatively high throughput using fully automated equipment. Other behaviours such as sleep and circadian rhythms, learning and memory and nociception can also be assessed. New technological advances in non-invasive imaging and neurochemical analyses have meant that these techniques can be readily applied to mouse phenotyping. The use of these screens together with mutagenesis is already beginning to increase the numbers of mouse models of potential relevance to CNS diseases. (+info)
Accuracy of tetrode spike separation as determined by simultaneous intracellular and extracellular measurements.
Simultaneous recording from large numbers of neurons is a prerequisite for understanding their cooperative behavior. Various recording techniques and spike separation methods are being used toward this goal. However, the error rates involved in spike separation have not yet been quantified. We studied the separation reliability of "tetrode" (4-wire electrode)-recorded spikes by monitoring simultaneously from the same cell intracellularly with a glass pipette and extracellularly with a tetrode. With manual spike sorting, we found a trade-off between Type I and Type II errors, with errors typically ranging from 0 to 30% depending on the amplitude and firing pattern of the cell, the similarity of the waveshapes of neighboring neurons, and the experience of the operator. Performance using only a single wire was markedly lower, indicating the advantages of multiple-site monitoring techniques over single-wire recordings. For tetrode recordings, error rates were increased by burst activity and during periods of cellular synchrony. The lowest possible separation error rates were estimated by a search for the best ellipsoidal cluster shape. Human operator performance was significantly below the estimated optimum. Investigation of error distributions indicated that suboptimal performance was caused by inability of the operators to mark cluster boundaries accurately in a high-dimensional feature space. We therefore hypothesized that automatic spike-sorting algorithms have the potential to significantly lower error rates. Implementation of a semi-automatic classification system confirms this suggestion, reducing errors close to the estimated optimum, in the range 0-8%. (+info)
Common data model for neuroscience data and data model exchange.
OBJECTIVE: Generalizing the data models underlying two prototype neurophysiology databases, the authors describe and propose the Common Data Model (CDM) as a framework for federating a broad spectrum of disparate neuroscience information resources. DESIGN: Each component of the CDM derives from one of five superclasses-data, site, method, model, and reference-or from relations defined between them. A hierarchic attribute-value scheme for metadata enables interoperability with variable tree depth to serve specific intra- or broad inter-domain queries. To mediate data exchange between disparate systems, the authors propose a set of XML-derived schema for describing not only data sets but data models. These include biophysical description markup language (BDML), which mediates interoperability between data resources by providing a meta-description for the CDM. RESULTS: The set of superclasses potentially spans data needs of contemporary neuroscience. Data elements abstracted from neurophysiology time series and histogram data represent data sets that differ in dimension and concordance. Site elements transcend neurons to describe subcellular compartments, circuits, regions, or slices; non-neuroanatomic sites include sequences to patients. Methods and models are highly domain-dependent. CONCLUSIONS: True federation of data resources requires explicit public description, in a metalanguage, of the contents, query methods, data formats, and data models of each data resource. Any data model that can be derived from the defined superclasses is potentially conformant and interoperability can be enabled by recognition of BDML-described compatibilities. Such metadescriptions can buffer technologic changes. (+info)