Inhibition of Alzheimer's disease beta-amyloid aggregation, neurotoxicity, and in vivo deposition by nitrophenols: implications for Alzheimer's therapy.
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Alzheimer Disease↗
Biomedical subjects
J C Houzel
Publications and source records attributed to J C Houzel.
Visual interhemispheric transfer to areas 17 and 18 in cats with convergent strabismus.
Commissural connections between primary visual cortical maps of the two hemispheres are essential to unify the split representation of the visual field. In normal adult cats, callosal connections are essentially restricted to the border between areas A17 and A18, where the central vertical meridian is projected. In contrast, early convergent strabismus leads to an expanded callosal-receiving zone, as repeatedly indicated by anatomical experiments. We investigated here the functional correlates of this widespread distribution of callosal terminals by analysing transcallosal visual responses in five anaesthetized and paralysed 4-10-month-old cats whose right eye had been surgically deviated on postnatal day 6. After acute section of the optic chiasm, single-unit activity was recorded from A17 and A18 of the right hemisphere while the left eye was visually stimulated. A total of 108/406 units were transcallosally activated. While they were more frequent at the 17/18 border (46% of the units recorded within this region), numerous transcallosally activated units were located throughout A17 (16%), A18 (27%) or within the white matter (17%). In all regions, transcallosally driven units displayed functional deficits usually associated with strabismus, such as decreased binocularity and ability to respond to fast-moving stimuli, and increased receptive field size. Many units also displayed reduced orientation selectivity and increased position disparity. In addition, transcallosal receptive fields were manifestly located within the hemifield ipsilateral to the explored cortex, with almost no contact with the central vertical meridian. Comparison with data from normal adults revealed that strabismus induced a considerable expansion of the callosal receiving zone, both in terms of the cortical region and of the extent of the visual field involved in interhemispheric transfer, with implications in the integration of visual information across the hemispheres.
Animals↗
Maxsim, software for the analysis of multiple axonal arbors and their simulated activation.
In order to analyze the structural organization of complex axonal arbors reconstructed from histological serial sections, and to investigate the functional implications of their geometrical properties, we developed software providing the following facilities: (1) direct importation of data files generated by a commercially available 3-D light-microscopic reconstruction system, including routine procedures for identification and correction of data acquisition errors; (2) real-time 3-D rotations of the arbors in the stack of serial sections; (3) multiple interactive display modes; (4) possibility of modifying diameter and/or connectivity of different branches; (5) simulation of the invasion of the arbor by a single action potential initiated at any chosen point, and visualization of spatio-temporal profiles of activation; (6) extraction of quantitative data converted to standard file formats compatible with available mathematical software. All these tools can be applied to single or multiple axons, individually or simultaneously. The software, called Maxsim, is a highly flexible C-written program running on graphical workstations using the UNIX operating system and X-Window environment.
Animals↗
Morphology of callosal axons interconnecting areas 17 and 18 of the cat.
Seventeen callosally projecting axons originating near the border between areas 17 and 18 in adult cats were anterogradely labelled with biocytin and reconstructed in 3-D from serial sections. All axons terminated near the contralateral 17/18 border. However, they differed in their diameter, tangential and radial distributions, and overall geometry of terminal arbors. Diameters of reconstructed axons ranged between 0.45 and 2.25 microns. Most of the axons terminated in multiple terminal columns scattered over several square millimetres of cortex. Thus in general callosal connections are not organized according to simple, point-to-point spatial mapping rules. Usually terminal boutons were more numerous in supragranular layers; some were also found in infragranular layers, none in layer IV. However, a few axons were distributed only or mainly in layer IV, others included this layer in their termination. Thus, different callosal axons may selectively activate distinct cell populations. The geometry of terminal arbors defined two types of architecture, which were sometimes represented in the same axon: parallel architecture was characterized by branches of considerable length which supplied different columns or converged onto the same column; serial architecture was characterized by a tangentially running trunk or main branch with radial collaterals to the cortex. These architectures may relate to temporal aspects of inter-hemispheric interactions. In conclusion, communication between corresponding areas of the two hemispheres appears to use channels with different morphological and probably functional properties.
Animals↗
Computational structure of visual callosal axons.
We analysed the activation profiles obtained by simulating invasion of an orthodromic action potential in eleven anterogradely filled and serially reconstructed terminal arbors of callosal axons originating and terminating in areas 17 and 18 of the adult cat. This was done in order to understand how geometry relates to computational properties of axons. In the simulation, conduction from the callosal midline to the first bouton caused activation latencies of 0.9-3.2 ms, compatible with published electrophysiological values. Activation latencies of the total set of terminal boutons varied across arbors between 0.3 and 2.7 ms. Arbors distributed boutons in tangentially segregated terminal columns spanning one or, more often, several layers. Individual columns of one axon were frequently activated synchronously or else with a few hundred microseconds of each other. Synchronous activation of spatially separate columns is achieved by: (i) long primary or secondary branches of similar calibre running nearly parallel to each other for several millimetres; (ii) variations in the calibre of branches serially fed to separate columns by the same primary or secondary branch; (iii) exchange of high-order or preterminal branches across columns. The long, parallel branches blatantly violate principles of axonal economy. Simulated alterations of the axonal arbors indicate that similar spatiotemporal patterns of activity could, in principle, be obtained by less axon-costly architectures. The structure of axonal arbors, therefore, may not be determined solely by the type of spatiotemporal activation profiles it achieves in the cortex but also by other constraints, in particular those imposed by developmental mechanisms.
Action Potentials↗
Pattern of development of the callosal transfer of visual information to cortical areas 17 and 18 in the cat.
The aim of this study was to investigate the development of visual callosal transfer in the normally reared cat. Two- to nine-week-old kittens and adults (used as controls) underwent section of the optic chiasm. Three days later, the animals were placed under anesthesia and paralysed; unit activities were recorded from visual cortical areas 17 and 18 and from the white matter in one hemisphere. The units were tested for their responses to visual stimulation of each eye successively. Out of 1036 recorded neurons, 185 could be activated through the eye contralateral to the explored cortex via callosal transfer. Most of them could also be driven through the ipsilateral eye via the 'direct' geniculo-cortical pathway. For animals aged > or = 2 weeks, virtually all of these units were located at the 17/18 border zone, with a majority in the supragranular layers. When activated through the corpus callosum, they displayed receptive fields located either on the central vertical meridian of the visual field or in the hemifield ipsilateral to the explored cortex. Such extension into the ipsilateral hemifield as well as receptive field disparities of binocular units decreased with age, while spontaneous activity, strength of response, orientation selectivity and ability to respond to slits moving at middle-range velocity increased. The main conclusion is that the transient callosal projections described by anatomists, which are present until 3 months of age, do not achieve supraliminar synaptic contacts with parts of areas 17 and 18 other than the 17/18 border zone, at least from 12 days after birth. However the visual callosal transfer in young animals displays some characteristics which disappear with age.
Aging↗
Visual inter-hemispheric processing: constraints and potentialities set by axonal morphology.
The largest bundle of axonal fibers in the entire mammalian brain, namely the corpus callosum, is the pathway through which almost half a billion neurons scattered over all neocortical areas can exert an influence on their contralateral targets. These fibers are thus crucial participants in the numerous cortical functions requiring collaborative processing of information across the hemispheres. One of such operations is to combine the two partial cortical maps of the visual field into a single, coherent representation. This paper reviews recent anatomical, computational and electrophysiological studies on callosal connectivity in the cat visual system. We analyzed the morphology of individual callosal axons linking primary visual cortices using three-dimensional light-microscopic techniques. While only a minority of callosal axons seem to perform a strict 'point-to-point' mapping between retinotopically corresponding sites in both hemispheres, many others have widespread arbors and terminate into a handful of distant, radially oriented tufts. Therefore, the firing of a single callosal neuron might influence several cortical columns within the opposite hemisphere. Computer simulation was then applied to investigate how the intricate geometry of these axons might shape the spatio-temporal distribution of trans-callosal inputs. Based on the linear relation between diameter and conduction velocity of myelinated fibers, the theoretical delays required for a single action potential to reach all presynaptic boutons of a given arbor were derived from the caliber, g-ratio and length of successive axonal segments. This analysis suggests that the architecture of callosal axons is, in principle, suitable to promote the synchronous activation of multiple targets located across distant columns in the opposite hemisphere. Finally, electrophysiological recordings performed in several laboratories have shown the existence of stimulus-dependent synchronization of visual responses across the two hemispheres. Possible implications of these findings are discussed in the context of temporal tagging of neuronal assemblies.
Animals↗