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[Spatial reorganization of horizontal connections of cat cortical area 17 induced by eye rotation].

In six cats with experimental unilateral or bilateral strabismus, surgically induced early in postnatal life, torsion eye rotation with a deviation angle of 10 to 20 degrees was also detected. Spatial distribution of retrogradely labeled neurons in area 17 was studied following microiontophoretic injection of horseradish peroxidase in area 17 or 18 cortical columns. Eye rotation was shown to cause the increase of the length of horizontal neuronal connections in area 17 along the projection of visual field vertical meridian. The reorganization of neuronal connections, detected in this work, may promote the functional changes, described in the literature, that compensate for the eye rotation.

Animals↗

Connections of neurons in the lumbar ventral horn of spinal cord are altered after long-standing limb loss in a macaque monkey.

Explanations for the massive reorganization in primary motor cortex, M1, after limb amputation typically focus on processes that occur in cortex. Few have investigated whether changes in more peripheral parts of the pathway might also play a role in the reorganization. In the present study, we examined the integrity and connectivity of the spinal cord motoneurons in a macaque monkey (Macaca mulatta) that lost a hindlimb as a result of accidental injury more than 3.5 years earlier. To label motoneurons, multiple small injections of a neuroanatomical tracer were placed in the muscles of the hip just adjacent to the stump of the amputated leg, and in matched locations in the opposite side for control purposes. Injections of a second tracer were made in the intact foot. In the ventral horn that related to the intact hindlimb, motoneurons labeled by the hip injections were concentrated rostral and ventromedial to those labeled by the foot injections. Hip injections on the side of the amputation labeled neurons that were located well beyond the normal territory for motoneurons related to the hip and into the zone normally occupied by neurons projecting to the foot. Labeled motoneurons innervating the intact limb were significantly larger than neurons on the side of the amputation (x = 2410 and 2061 microm(2), respectively). The findings suggest that many neurons survived the long-standing amputation, and made new connections with remaining intact muscles. These new patterns of connectivity likely contribute to the reorganization of motor cortex in amputees, and perhaps to abnormal behaviors like those reported by human amputees.

Amputation, Surgical↗

How do cell assemblies encode information in the brain?

The present review discusses why cell-assembly coding, i.e. ensemble coding by functionally connected neurons, is a tenable view of the brain's neuronal code and how it operates in the working brain. The cell-assembly coding has two major properties, i.e., partial overlapping of neurons among assemblies and connection dynamics within and among the assemblies. The former is the ability of one neuron to participate in different types of information processing. The latter is the capability for functional synaptic connections, detected by activity correlations of the neurons, to change among different types of information processing. An example of a series of experiments which detected these two major properties is then given. Several relevant points concerning the detection of the actual dynamics of cell-assembly coding are also enumerated. They include the dependence of the type of cell-assembly coding on types of information-processing in different structures of the brain, sparse coding by distributed overlapped assemblies, and coincidence detection as a role of individual neurons to bind distributed neurons into cell assemblies.

Animals↗

BDNF modulates, but does not mediate, activity-dependent branching and remodeling of optic axon arbors in vivo.

The proper development of axon terminal arbors and their recognition of target neurons depend, in part, on neuronal activity. Neurotrophins are attractive candidate signals to participate in activity-dependent development and refinement of neuronal connectivity. In the visual system, brain-derived neurotrophic factor (BDNF) has been shown to modulate the elaboration and refinement of axonal arbors and to participate in the establishment of topographically ordered visual maps. By examining in vivo with time-lapse microscopy the effects of activity blockade and BDNF on optic axon arborization, I show that the dynamic mechanisms by which neurotrophins and neuronal activity regulate axon arborization differ. Acute retinal activity blockade by intraocular injection of tetrodotoxin (TTX) rapidly and significantly increased branch addition and elimination, thus interfering with axon branch stabilization. The effects of activity blockade on branch dynamics resulted in increased arbor complexity in the long term and were prevented by altering endogenous BDNF levels at the target. BDNF promoted axon arborization by increasing branch addition and lengthening, without affecting branch elimination. Activity blockade, however, did not prevent the growth-promoting effects of BDNF, indicating that BDNF can affect axon arborization even in the absence of activity. Together this evidence indicates that BDNF acts as a modulator, but not as a direct mediator, of activity during the morphological development of neurons. Consequently, neuronal activity and BDNF use distinct but interactive mechanisms to control the development of neuronal connectivity; BDNF modulates axon arborization by promoting growth, neuronal activity participates in axon branch stabilization, and together these two signals converge to shape axon form.

Action Potentials↗

Reverse optical probing (ROPING) of neocortical circuits.

We describe an optical technique to detect circuits of synaptically connected neurons. By combining calcium imaging of the spontaneous activity of neuronal populations with intracellular recordings from a given neuron, we perform a type of reverse correlation analysis to detect neurons that generate action potentials time-locked to the synaptic currents of the recorded cell. This technique can quickly reveal monosynaptically connected neurons.

Animals↗

Effect of lateral connections on the accuracy of the population code for a network of spiking neurons.

We study how neuronal connections in a population of spiking neurons affect the accuracy of stimulus estimation. Neurons in our model code for a one-dimensional orientation variable phi. Connectivity between two neurons depends on the absolute difference absolute value(phi - phi') between the preferred orientation of the two neurons. We derive an analytical expression of the activity profile for a population of neurons described by the spike response model with noisy threshold. We estimate the stimulus orientation and the trial-to-trial fluctuations using the population vector method. For stationary stimuli, uniform inhibitory connections produce a more reliable estimation of the stimulus than short-range excitatory connections with long-range inhibitions, although the latter interaction type produces a sharper tuning curve. These results are consistent with previous analytical studies of the Fisher information.

Action Potentials↗

[Neuron-vascular connections in the superior geniculate body and anterior bigeminal body of cats after acceleration].

Thirty-nine cats were exposed to acceleration of 10 g for one or several days. Their neuronal-vascular relations in the subcortical optic centers were investigated using ink-gelatin injections and Nissl's method. During one-day back-to-chest, chest-to-back and head-to-feet acceleration and many-day head-to-feet and chest-to-back acceleration neuronal-vascular relations decreased, whereas during one-day feet-to-head and many-day, chest-to-back and feet-to-head acceleration they increased. During one-day centrifugation edematous neurons and during many-day centrifugation swollen neurons may occur.

Acceleration↗

Eye-rotation-induced spatial reorganization of horizontal connections in field 17 of the cat cortex.

Six cats with rotation of one or both eyes (strabismus) produced surgically in the early postnatal period demonstrated torsional deviation of the eyes by 10-20 degrees in addition to the rotation. The spatial distribution of retrograde labeled neurons in field 17 was studied by microiontophoretic administration of horseradish peroxidase into individual cortical columns in fields 17 and 18. These studies showed that rotation of the eyes increased the extent of horizontal neuronal connections in field 17 along the projection of the vertical meridian of the field of vision. It is suggested that this reorganization of neuronal connections may support functional changes compensating for eye rotation, as described in the literature.

Animals↗

The influence of acetylcholine and atropine on the temporary connection in neuronal populations of the motor cortex.

The activity of neurons of the sensorimotor cortex during the paired combination of stimulations of brain structures (the medial lemniscus, the reticular nucleus of the midbrain tegmentum, and the pyramidal tract), with an interstimulus interval of 1.2 sec, was investigated in awake nonimmobilized rabbits. During the omission of the reinforcing stimulus at a place of its expected delivery, a complicated complex of reorganizations of the impulse activity of the neurons develops, consisting of the reproduction of responses and changes in impulse activity which differ in configuration from them, and which usually appear at later periods. The direct application of acetylcholine to the cortex facilitates the manifestation of both types of reorganizations of the neuronal activity. The application, on the other hand, of atropine suppresses primarily the second type of reorganizations. In addition, acetylcholine increases the total duration of these electrical indices of the temporary connection of the developed reactions, while atropine decreases it.

Acetylcholine↗

Cadherins: molecular codes for axon guidance and synapse formation.

The formation of the myriad of neuronal connections within the vertebrate nervous system relies on expression of molecular tags that match extending axon populations with synaptic target sites. Recent work suggests that cadherins, a group of calcium-dependent cell adhesion molecules, are candidates to serve such a role. The diversity of the cadherin family in the nervous system allows for a multitude of interactions to specify neuronal connections. Specific cadherin types demarcate subpopulations of developing axons that interconnect within neuronal circuits. Expression of different cadherin species at select synapse populations raises exciting prospects for this molecule class in controlling adhesive interactions during synaptogenesis and plasticity. Regulation of cadherin-mediated adhesive strength is an attractive mechanism to explain the different cadherin functions in axon growth and at synapses.

Animals↗

Morphology of individual axons in crossed corticorubral projections in developing cats and effects of partial denervation.

Ordered neuronal connections in mature brains are thought to be sculpted from initially diffuse projections by elimination of inappropriate projections and strengthening of appropriate ones. Although evidence suggests that neuronal activity plays a role in these processes, the mechanism behind the modification of neuronal connections remains obscure. To gain insight into the mechanisms of axonal elimination and projection strengthening, we examined the morphology of individual axons that were to be eliminated as well as the consequences of partial denervation. While corticorubral projections in adult cats are thought to be uncrossed, early in postnatal development and after early unilateral lesions to the sensorimotor cortex, however, a significant amount of crossed corticorubral projections occurs. We examined the morphology of individual corticorubral axons in fetal cats and kittens from embryonic day 59 to postnatal day 48 and those that had received early unilateral lesions to the cortex, by serial reconstruction of Phaseolus-vulgaris-leucoagglutinin- or biocytin-labeled axons. For about 2 weeks during pre- and postnatal development, crossed axons remained simple in morphology, with few branches. Thereafter, they showed an increase in branch number, but then began to show fewer branches again. Axons and their collaterals were found in nonrestricted areas of the red nucleus (RN) throughout the period of observation, indicating that axons can sit at an inappropriate target for weeks but fail to ramify. In contrast, crossed corticorubral axons in kittens with cortical lesions showed terminal-arbor-like structures in the RN region that are in mirror symmetry to topographically appropriate areas in the ipsilateral RN, although some showed simple morphology without arbors. These complicated forms of morphology of individual axons during development and after partial denervation may not be explained by a simple activity-dependent mechanism.

Animals↗

An artificial neural network analogue of learning in autism.

An artificial neural network is simulated that shares formal qualitative similarities with the selective attention and generalization deficits seen in people with autism. The model is based on neuropathological studies which suggest that affected individuals have either too few or too many neuronal connections in various regions of the brain. In simulations where the model was taught to discriminate children with autism from children with mental retardation, having too few simulated neuronal connections led to relatively inferior discrimination of the two groups in a training set and, consequently, relatively inferior generalization of the discrimination to a novel test set. Too many connections produced excellent discrimination but inferior generalization because of overemphasis on details unique to the training set. It is concluded that, within the context of the current model, the neuropathological observations that have been described in the literature are sufficient to explain some of the unique pattern recognition and discrimination learning abilities seen in some people with autism as well as their problems with generalization and concept acquisition. The model generates testable hypotheses that have implications for understanding the pathogenesis, treatment, and phenomenology of autism.

Analysis of Variance↗

Excitatory cortical neurons form fine-scale functional networks.

The specificity of cortical neuron connections creates columns of functionally similar neurons spanning from the pia to the white matter. Here we investigate whether there is an additional, finer level of specificity that creates subnetworks of excitatory neurons within functional columns. We tested for fine-scale specificity of connections to cortical layer 2/3 pyramidal neurons in rat visual cortex by using cross-correlation analyses of synaptic currents evoked by photostimulation. Recording simultaneously from adjacent layer 2/3 pyramidal cells, we find that when they are connected to each other (20% of all recorded pairs) they share common input from layer 4 and within layer 2/3. When adjacent layer 2/3 neurons are not connected to each other, they share very little (if any) common excitatory input from layers 4 and 2/3. In contrast, all layer 2/3 neurons share common excitatory input from layer 5 and inhibitory input from layers 2/3 and 4, regardless of whether they are connected to each other. Thus, excitatory connections from layer 4 to layer 2/3 and within layer 2/3 form fine-scale assemblies of selectively interconnected neurons; inhibitory connections and excitatory connections from layer 5 link neurons across these fine-scale subnetworks. Relatively independent subnetworks of excitatory neurons are therefore embedded within the larger-scale functional architecture; this allows neighbouring neurons to convey information more independently than suggested by previous descriptions of cortical circuitry.

Action Potentials↗

The cerebral and cerebellar connections of pretecto-thalamic and pretecto-olivary neurons in the anterior pretectal nucleus of the cat.

The neuronal connections of the anterior pretectal nucleus (PTA) were investigated in the cat. For the light microscopy, the retrograde double-labeling technique by means of Fluoro-Gold (FG) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP) was used. Following injections of one tracer into the central lateral nucleus of the thalamus (CL) and the other into the dorsal accessory olivary nucleus (DAO), distributions of labeled neurons in the PTA were observed. Most of the labeled neurons were single-labeled either with FG or with WGA-HRP. The result indicated that pretecto-thalamic projection neurons were distributed throughout the whole extent of the PTA, whereas pretecto-olivary projection neurons were located in a restricted area of the ventral part of the PTA. Only a very small number of double-labeled neurons were found in the PTA. These two efferent projections thus seemed to be derived from different populations of PTA neurons. For the electron microscopy, a combination of retrograde transport of horseradish peroxidase (HRP) and anterograde degeneration technique was used. After HRP injections into the CL combined with lesions either in the motor cortex (MCx) or in the anterior interpositus nucleus of the cerebellum (Cbl), some degenerating axon terminals originating from the cerebrum or cerebellum were found to synapse with retrogradely labeled pretecto-thalamic projection neurons. We have already observed direct cerebral and cerebellar projections to the pretecto-olivary projection neurons (J. Comp. Neurol., 259 (1987) 348-363). We conclude that the two different populations of PTA neurons comprise two different kinds of neuronal circuitries, i.e. MCx-PTA-CL-MCx and Cbl-PTA-DAO-Cbl, and that these two circuitries might interrelate with each other in the PTA at the cellular level.

Animals↗

Anatomical evidence for a bi-neuronal pathway connecting the nucleus tractus solitarius to caudal ventrolateral medulla to rostral ventrolateral medulla in the rat.

Using tract tracing techniques and dual-color histochemistry, this study investigated connections between the nucleus tractus solitarius (NTS), caudal ventrolateral medulla (CVLM), and rostral ventrolateral medulla (RVLM) in the rat. The anterograde tracer biotinylated dextran amine (BDA) was deposited into the NTS. The retrograde tracer Fluoro-Gold was deposited into the RVLM. In the CVLM, Fluoro-Gold-labeled cells were found intermingled with anterogradely labeled fibers coursing from the NTS. BDA-labeled axons, varicosities, and boutons were observed in close apposition to retrogradely labeled neurons in the CVLM. These data provide anatomical evidence for a bi-neuronal pathway from NTS to CVLM to RVLM; and support the hypothesis that these connections may comprise the medullary baroreceptor reflex pathway.

Animals↗

Cytoarchitecture and topographic projections of the gustatory centers in a teleost, Carassius carassius.

The neuronal connections in the central gustatory system of the crucian carp were examined by means of degeneration and HRP methods. Cell morphology in the primary gustatory lobes was studied in Golgi-impregnated material. Medium-sized neurons of the facial lobe emit axons which project to the secondary gustatory nucleus. The nucleus intermedius facialis of Herrick ('05) projects bilaterally. Large neurons send axons through the spinal trigeminal tract to terminate in the spinal trigeminal nucleus and in the medial funicular nucleus. In the vagal lobe, second-order neurons for the ascending projections are located in the superficial part of the sensory zone. These neurons project exclusively to the ipsilateral secondary gustatory nucleus. Neurons located in the deeper part of the sensory zone send axons to the motor zone and to the brainstem reticular formation to form short reflex arcs. The glossopharyngeal lobe has similar neuronal connections to the vagal sensory zone. Both facial and vagal lobes receive afferent projections from the following central structures: nucleus posterioris thalami, nucleus diffusus lobi inferioris, optic tectum, motor nucleus of the trigeminal nerve, medullary reticular formation, and the gray matter of the upper spinal cord. The facial lobe has an additional afferent from the mesencephalic reticular formation. The major sources to the medullary gustatory lobes are the nucleus posterioris thalami and nucleus diffusus lobi inferioris. Each type of neuron classified by morphology and location in the facial, glossopharyngeal, and vagal lobes was correlated with its particular destination. Topographic projections were demonstrated in the secondary and tertiary gustatory centers.

Afferent Pathways↗

Constraining the connectivity of neuronal networks cultured on microelectrode arrays with microfluidic techniques: a step towards neuron-based functional chips.

In vitro culture of small neuronal networks with pre-defined topological features is particularly desirable when the electrical activity of such assemblies can be monitored for long periods of time. Indeed, it is hoped that such networks, with pre-determined connectivity, will provide unique insights into the structure/function relationship of biological neural networks and their properties of self-organization. However, the experimental techniques that have been developed so far for that purpose have either failed to provide very long-term pattern definition and retention, or they have not shown potential for integration into more complex microfluidic devices. To address this problem, three-dimensional microfluidic systems in poly(dimethylsiloxane) (PDMS) were fabricated and used in conjunction with both custom-made and commercially available planar microelectrode arrays (pMEAs). Various types of primary neuronal cell cultures were established inside these systems. Extracellular electrical signals were successfully recorded from all types of cells placed inside the patterns, and this bioelectrical activity was present for several weeks. The advantage of this approach is that it can be further integrated with microfluidic devices and pMEAs to yield, for example, complex neuron-based biosensors or chips for pharmacological screening.

Action Potentials↗

Axon navigation in the mammalian primary olfactory pathway: where to next?

The process of establishing long-range neuronal connections can be divided into at least three discrete steps. First, axons need to be stimulated to grow and this growth must be towards appropriate targets. Second, after arriving at their target, axons need to be directed to their topographically appropriate position and in some cases, such as in cortical structures, they must grow radially to reach the correct laminar layer. Third, axons then arborize and form synaptic connections with only a defined subpopulation of potential post-synaptic partners. Attempts to understand these mechanisms in the visual system have been ongoing since pioneer studies in the 1940s highlighted the specificity of neuronal connections in the retino-tectal pathway. These classical systems-based approaches culminated in the 1990s with the discovery that Eph-ephrin repulsive interactions were involved in topographical mapping. In marked contrast, it was the cloning of the odorant receptor family that quickly led to a better understanding of axon targeting in the olfactory system. The last 10 years have seen the olfactory pathway rise in prominence as a model system for axon guidance. Once considered to be experimentally intractable, it is now providing a wealth of information on all aspects of axon guidance and targeting with implications not only for our understanding of these mechanisms in the olfactory system but also in other regions of the nervous system.

Animals↗