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H Axelrad

Publications and source records attributed to H Axelrad.

At least 19 recordsLinked to original sources
PubMed2004

The cerebellar second homunculus remains silent during passive bimanual movements.

In a previous study, we showed that the second homunculus in lobule VIII of the cerebellum is activated during bilateral out-of-phase index finger-thumb opposition, implying a role in motor coordination. However, several recent studies indicate that the cerebellum could be more actively involved in sensory information processing during movement. Therefore, as lobule VIII activation could involve either a motor or a proprioceptive component, these two components must be distinguished and their relative contribution must be determined. Using functional imaging, we studied cerebellar activation of the same region during passively induced index finger-thumb opposition of both hands in in-phase and out-of-phase modes, thereby excluding the voluntary movement component. No significant activation was detected in lobule VIII. Intense activation of lobule VIII, obtained during active, out-of-phase bimanual movements, therefore does not involve a significant sensory component related to direct proprioceptive feedback. This result is strongly in favour of the specific recruitment of lobule VIII during out-of-phase movements related more to complex motor timing than to sensory function.

Adult↗
PubMed2004

Specific neocerebellar activation during out-of-phase bimanual movements.

We used fMRI to study cerebellar activation during index finger-thumb opposition of the right hand and index finger-thumb opposition of both hands in in-phase and out-of-phase modes. The right hand movement activates the contralateral anterior lobe of the cerebellum. During bimanual in-phase movements, this activity pattern becomes bilateral. More interestingly, bilateral out-of-phase movements recruit the cerebellar posterior lobe VIII, which likely corresponds to the second homunculus. As out-of-phase movements differ from the in-phase movements only by their temporal complexity and their attentional awareness, this study demonstrates the preferential involvement of the cerebellar second homunculus in the control of complex movements.

Adult↗
PubMed2002

Extending the cerebellar Lugaro cell class.

We describe here, in Golgi-impregnated rat cerebellar cortex, a new group of large granular layer neurons. These cells have a globular soma located at variable depths in the granular layer, and three to four long radiating dendrites coursing through the three layers of the cortex. The axon projects more or less directly into the molecular layer, where it expands in a local plexus of oblique and tortuous thick collaterals ascending through the major part of the layer. Interestingly, the axons of several of these cells give off a collateral that courses for a long distance in the transverse direction, just above the Purkinje cell somata, parallel to the parallel fibers. While the granular layer location and the polymorphous somato-dendritic pattern of these cells is reminiscent of that of Golgi cells, their axonal pattern is clearly of the same type as that of another large granular layer interneuron, the Lugaro cell. Moreover, double anti-calretinin and anti-calbindin immunolabellings show that Lugaro cells as well as some globular somata dispersed in the granular layer are both calretinin-positive and in close apposition with numerous calbindin-positive varicosities of Purkinje cell axon recurrent collaterals. These latter are known from previous ultrastructural studies to be pre-synaptic to Lugaro cells. The common granular layer location and calretinin labelling, the striking similarity in axonal projection pattern, and the important common recurrent afferentation by Purkinje cell axons strongly argue in favor of the classification of these globular interneurons as a subgroup of a widened Lugaro cell type.

Animals↗
PubMed2001

Cellular and subcellular morphological localization of normal prion protein in rodent cerebellum.

Normal cellular prion protein, a necessary protagonist in fatal neurodegenerative prion diseases, was mapped in rodent cerebellum to establish its cellular and ultrastuctural localization. Existing morphological data about native prion protein distribution in brain tissues remain, indeed, contradictory and do not fit with biochemical and cell biological results. Using ultrastructural preembedding immunocytochemistry and a monoclonal anti-mouse prion protein antibody, this report shows that cellular prion protein is present in all cortico-cerebellar and deep nuclei neuronal cell types, as well as in all glial cell types. The heaviest expression appears on parallel fibres and astrocytic processes. The protein is exclusively located on the outer cell membrane and in Golgi and endosomal intracytoplasmic organelles, with no cytoplasmic or synaptic vesicle labelling. Most important, and in contrast with previous ultrastructural data, cellular prion protein is shown to be distributed on all portions of neurons, without any preferential synaptic targeting. The present morphological report shows, for the first time in vivo, that the cellular prion protein is present on the entire cell surface membrane of all neuronal and glial cell types of the rat cerebellum. This ubiquitous presence supports the notion that prion protein has a generalized cellular function in brain tissue rather than a specialized role restricted to synaptic transmission.

Animals↗
PubMed1998

Lugaro cells target basket and stellate cells in the cerebellar cortex.

Lugaro cells are fusiform neurons located just beneath the Purkinje cell layer. Their axon projects profusely in the molecular layer and emits some collaterals in the granular layer. We have analysed the molecular layer postsynaptic targets of a Golgi-impregnated Lugaro cell, using the electronmicroscopic gold-toning procedure and post-embedding anti-GABA immunocytochemistry. All the gold-labeled neuritic and somatic profiles were GABA-positive, thus confirming that the Lugaro cell is an inhibitory interneuron. The axonal varicosities of this cell form multiple symmetrical synaptic junctions with basket and stellate cell somata and proximal dendrites, and, perhaps, with the molecular layer dendrites of Golgi interneurons. Lugaro cells thus seem to exert a feed-back inhibitory control on Purkinje cells.

Animals↗
PubMed1996

Morphology of the Golgi-impregnated Lugaro cell in the rat cerebellar cortex: a reappraisal with a description of its axon.

We present a detailed description of the somatodendritic and axonal features of the Golgi-impregnated Lugaro cell in the rat cerebellar cortex. This neuron, present throughout the cerebellum, is characterized by a fusiform cell body located at the border between the granular and Purkinje cell layers, horizontal bipolar dendrites extending in the parasagittal plane and an axon projecting exclusively to the molecular and granular layers. A quantitative analysis of 77 Lugaro cells confirms the somatodendritic homogeneity of this cell type. Computer reconstructions showed that the bipolar dendrites spread like an horizontal X centered by the cell body, implying that Lugaro cells are arranged in a flat lattice just beneath the Purkinje cell layer. Fifty-seven Lugaro cells with sufficiently impregnated axons displayed a common pattern of organization with, nevertheless, a certain variability of the axonal trajectory. Some axons projected directly into the molecular layer with a profuse plexus spreading just above the parent cell. Other axons first traveled downwards into the granular layer, sometimes even reaching and passing into the white matter. They always hooked back to reascend through the granular layer and also finally terminate in the molecular layer, near and sometimes at a distance from the parent cell. In a few samples, one or two remote axon collaterals were seen to extend longitudinally in the lower molecular layer for a few hundred microns, in the same direction as the parallel fibers. In all cases a few collaterals projected into the granular layer. In view of its dense afferentation by Purkinje cell recurrent collaterals and its profuse inhibitory projection in the molecular layer, the Lugaro cell could act as a feedback interneuron on the corticocerebellar output.

Animals↗
PubMed1994

Granular layer collaterals of the unipolar brush cell axon display rosette-like excrescences. A Golgi study in the rat cerebellar cortex.

The unipolar brush cell (UBC) is a medium-sized neuron located in the granular layer of the cerebellar cortex and morphologically characterized by a single dendritic shaft terminated by a brush-like tuft [Mugnaini and Floris, J. Comp. Neurol., in press]. This neuronal class is mostly encountered in the vestibular part of the cerebellum, although also present in the rest of the vermal folia. The UBC axon, as seen in Golgi impregnated material, has a tortuous course throughout the granular layer and gives off number of collaterals of variable diameter. Some of the axon collaterals enter the white matter only for a short distance, after which they ascend into the granular layer. Astonishingly, some of the thick granular collaterals of these axons display characteristic expansions resembling the rosette excrescences seen on mossy fibers. In our series these rosettes are mostly of the simple type [Palay, S. and Chan-Palay, V., Cerebellar Cortex. Cytology and Organization, Springer, Berlin, 1974], i.e. short swellings with simple globular contours. The exact projection targets and functional effect of the UBC axon and granular rosettes have still to be demonstrated.

Animals↗
PubMed1994

The candelabrum cell: a new interneuron in the cerebellar cortex.

A new cell type is described in silver-impregnated sections of the rat cerebellar cortex, uniformly distributed through all the cerebellar folia. The soma is rather small, roughly pyriform, vertically oriented, and squeezed, in a sandwich-like manner, between the Purkinje cell somata. One or two thick dendrites arise from the upper pole of the cell body and course through the entire molecular layer, dividing into a few, slightly oblique, branches that can reach the pia mater. These dendrites are covered with irregularly distributed spines. Some more slender dendrites emerge from the lower part of the cell body, or from the proximal trunk of a molecular dendrite, and spread tortuously for a short distance in the upper granular layer. A thick initial segment emerges directly from the soma or from the proximal portion of a dendrite, the axon winding then horizontally through or just above the Purkinje cell layer. During this horizontal course it gives off vertically oriented beaded branches ascending through the major part of the molecular layer. These branches, rather closely spaced, occupy different parasagittal planes, separated by about 10 to 30 microns. This axonal arborisation can thus be compared with a candelabrum. The peculiar three-dimensional spread of the axonal collaterals suggests a functional relationship between these branches and the dendritic trunks of neighbouring Purkinje cells. A comparative analysis of the morphological differences between this candelabrum interneuron and the other corticocerebellar interneurons found in the vicinity of the ganglionic layer confirms the specificity of this new cell class.

Animals↗
PubMed1993

Effects of recurrent collateral inhibition on Purkinje cell activity in the immature rat cerebellar cortex--an in vivo electrophysiological study.

We present here a study on the effects of inhibitory recurrent collaterals of Purkinje cell (PC) axons on the activity of the immature rat cerebellar cortex. Simultaneous extracellular recordings of pairs of PCs were performed in rat pups aged 5-8 days postnatal. Bicuculline was applied to the surface of the cortex in order to functionally antagonize PC recurrent collaterals. At this early developmental stage these are the only inhibitory links in the network. Dye marks from the microelectrode tips and 3D serial-section reconstruction of the structure allowed the exact determination of the distance separating recorded cells and of their respective orientation in the cortex. Standard statistical tests and an informational entropy index were used to calculate levels of cooperativity. By comparing PC activity under control conditions and after bicuculline superfusion it is shown that recurrent collateral inhibition has a structurating effect on the PC activity and that it increases the informational content of the network. Inhibition decreases the activity of the cells by 35% and drastically changes the interspike interval histograms. This leads to a more constrained state of the system. Three types of coupling via recurrent collaterals are present: symmetrical, asymmetrical or non existent. The exact type of coupling follows a simple vicinity rule and strongly influences the cooperativity level between the recorded cells. This cooperativity was also found to be spatially compartmentalized. Several pairs were driven by common inputs via climbing fibers or parallel fibers. Using the predictive value of a theoretical model of this immature structure we propose a complementary explanation of the role of the recurrent collaterals at this stage of development: that of a spatial and temporal filter, specific to each different microzone.

Action Potentials↗
PubMed1993

Effects of collateral inhibition in a model of the immature rat cerebellar cortex: multineuron correlations.

A model of the immature rat cerebellar cortex is used to simulate the effect of the inhibitory recurrent collateral axons of the Purkinje cells on the spike trains in the network. Inhibition induces an important overall change in the statistical characteristics of individual spike trains. It is also instrumental in producing a strong cooperativity between the different neurons. Moreover, a functional spatial anisotropy appears. A specific entropy index is used to analyze levels of information transfer between clustered and faraway neurons in the network. The formatting effect of recurrent collateral inhibition on spike trains and on network functional dynamics is studied by means of a model of the newborn rat cerebellar cortex. This immature structure has simpler morphological characteristics and fewer physiological parameters than the adult one. It is thus a good candidate for the comparison between experimental and theoretical data. The model network is made of 256 formal neurons (FN), arranged in a square lattice. Each neuron is coupled to its eight nearest neighbors by inhibitory links. All the parameters of the different elements of the model--in particular integration of inhibitory and excitatory inputs--are given anatomical and physiological values derived from biological data. Activities of single FNs and correlations between spatially distant ones are analyzed with classical statistical techniques as well as with a specific informational entropy method we introduce. Simulation results indicate that inhibition is instrumental in: (1) the transformation of the spike train characteristics. This includes a lengthening of the mean interspike interval as well as an overall change in the statistical distribution of intervals, with an emergence of long-lasting ones; (2) the functional structuration of the network. Inhibitory connections between nearest neighbors induce a strong cooperativity between FNs. Furthermore a clear spatial anisotropy occurs in the functioning of the network, with inhibitory effects extending beyond local connectivity in preferential directions. We propose an interpretation of this functional structuration in terms of the various routes followed by the inhibition, including relay effects. The parameters of the model (levels of activities, inhibition rules and connectivities) were varied in order to test the robustness of the above results. Finally, the results are compared with those obtained in an experimental situation.

Animals↗
PubMed1992

Intermediate cells of Lugaro are present in the immature rat cerebellar cortex at an earlier stage than previously thought.

The maturation of the intermediate cell of Lugaro, impregnated by classical silver methods, was studied on parasagittal sections of cerebellar vermis of newborn rat pups. Using morphological criteria characteristic of the adult cell type, immature Lugaro neurons can be recognized from the second part of the first postnatal week on. This implies that these cells differentiate at a much earlier age than previously inferred from studies using tritiated thymidine.

Aging↗
PubMed1991

Propagation of parallel fiber volleys in the cerebellar cortex: a computer simulation.

We have studied the dynamic changes occurring during the propagation of active volleys through the parallel fiber (PF) tract in a portion of molecular layer of the cerebellar cortex, by means of a realistic computer simulation of the fibers (random distribution of PF origin; correlation between length and conduction velocity throughout depth). Surface electrical stimulations as well as mossy fiber stimulations of the PFs were mimicked. From a quantitative analysis of the propagation of the different types of volleys it appears that the constraints enforced by the morphological and functional characteristics of the PFs lead to an important spatial and temporal dispersion of the action potentials during their displacement along the folium. In particular, the time relationship between activity in the deep and superficial fibers as well as the number and location of active fibers at a given time (i.e. locus) will considerably vary during propagation. Moreover, in the case of a mossy fiber stimulation, there exists a striking asymmetry of the volleys travelling on each side of the site of stimulation. Therefore any information coded by the conjunctive activation of more than a few parallel fibers will be spatially and temporally dispersed in such a manner that successive postsynaptic Purkinje cells will receive very different combinations of inputs. This seems in favor of the hypothesis that these neurons function as coincidence detectors.

Action Potentials↗
PubMed1985

[Cerebellar cortex: simulation of recurrent collateral inhibition by means of a neuronal automata assembly. II. Temporal modulation and informational content].

A quantitative evaluation of the information content exhibited by a neuronal automata assembly coupled by collateral inhibitory--type rules was undertaken on the results of a computer simulation of this partial model of the cerebellar cortex. By comparison with an uncoupled array the model exhibited two main properties: A markovian type of behavior appears in the functioning of the system in as much as the appearance of a given state is strongly and exclusively correlated to the immediately preceding one. This behavior leads to a decrease in the entropy of the system. This implies that the informational content of the efferent "activity" is significantly higher than that of the afferent one.

Cerebellar Cortex↗
PubMed1985

[Cerebellar cortex: simulation of recurrent collateral inhibition with the aid of a set of neuronal automata. I. Model and global results].

In view of a study on the transfer function of the cerebellar cortex a modelization of each of the various subsystems was undertaken. The recurrent collateral inhibition existing between Purkinje cells was mimicked by means of an assembly of neuronal automata (NA) temporally evolving at random through three states ("silent", "tonic" and "phasic" and interacting with simple rules. In such an assembly--by comparison with a control group of independent NA--a drastic modulation of activity appears. First the total of the mean number of state shifts is increased by more than 10%. This increase is clearly hierarchical with a maximal effect for the "silent" state. Second the average duration of each state also varies, although in a contrasted manner. Third, and moreover, a clear spatial cooperativity emerges. Indeed all the individually coupled NA are in the same "silent" state at identical moments for more than 5.5% of the total running time. A cyclic repetition of this spatiotemporal cooperativity is apparent. The emergence of these collective properties--which can not be deduced linearly from the unitary elements--introduces a parameter of order leading to a coherent functioning of the system.

Animals↗
PubMed1980

Electrical inhibition of Purkinje cells in the cerebellum of the rat.

Monosynaptic activation of cerebellar Purkinje cells by a volley of parallel-fiber impulses is followed by a powerful disynaptic chemical inhibition mediated by molecular layer interneurons, including basket cells. Active zone established by basket preterminal axons on the body surface of the Purkinje cell account for this inhibition. However, morphological studies indicate that branches of the presynaptic fibers further descend along the initial segment of the Purkinje axon. Terminals from several basket cells converge and encapsulate each initial segment with a peculiar architectural structure that is reminiscent of that characterizing the axon cap of the teleost Mauthner cell. Because no function has yet been attributed to this pinceau, we have reanalyzed the successive Purkinje cell responses to activation of their presynaptic elements. Electrophysiological data provided by field-potential and single-unit measurements indicate that the classical phases of excitation and inhibition after a parallel-fiber volley are preceded by a brief inhibition of the Purkinje cells. Transmembrane hyperpolarizing potentials that exhibit the characteristics expected of electrically mediatd potentials underlie this early phase of inhibition; their properties are consistent with the hypothesis that they are generated by currents through terminals of nearby basket cells. Therefore, these hyperpolarizations, which are similar in their mechanism of generation to those described in the Mauthner cell system, represent a known case of electrical inhibition in the mammalian central nervous system.

Action Potentials↗
PubMed1977

[Organization in "barrels" of layer-IV cells of the S1 cortex in the mouse: effects of lesions or deprivation of the mystacial vibrissa].

In newborn mice the mystacial pads of the upper lips were submitted to different destructive or functionally reducing procedures. The effects on the barrels of the somato-sensory cortex were judged in mature animals and classified into 3 categories: 1. the barrels were present and normal; 2. the cortex was devoid of barrel structures; 3. the barrels were disorganized. Only procedures which involved peripheral lesions, and not those which reduced only the functional level, produced effects as deep as absence or disorganization of the barrels.

Animals↗