Eph and ephrin signaling in the formation of topographic maps

The axonal connections between the retina and its midbrain target, the superior colliculus (SC), is mapped topographically, such that the spatial relationships of cell bodies in the retina are maintained when terminating in the SC. Topographic map development uses a Cartesian mapping system such that each axis of the retina is mapped independently. Along the nasal-temporal mapping axis, EphAs and ephrin-As, are graded molecular cues required for topographic mapping while the dorsal-ventral axis is mapped in part via EphB and ephrin-Bs. Because both Ephs and ephrins are cell surface molecules they can signal in the forward and reverse directions. Eph/ephrin signaling leads to changes in cytoskeletal dynamics that lead to actin depolymerization and endocytosis guiding axons via attraction and repulsion.     

Plasticity and stability of somatosensory maps in thalamus and cortex

Work on elucidating the mechanisms of plasticity in somatosensory maps continues apace. Recent work has focused on both the nature of the thalamocortical interactions that determine plasticity, and on the differences between plasticity induced by nerve block or damage versus that induced by experience. Recordings from awake behaving animals have thrown light on the thalamocortical circuit mechanisms that underlie map plasticity; meanwhile, intracellular recordings from cortical slices have thrown light on the precise synaptic mechanisms underlying plasticity.     

Proprioceptive alignment of visual and somatosensory maps in the posterior parietal cortex

A touch on one hand can enhance the response to a visual stimulus delivered at a nearby location [1, 2], improving our interactions with the external world. In order to keep such visual-tactile spatial interactions effective, the brain updates the continuous postural changes, like those typically accompanying hand actions, through proprioception, thus maintaining the somatosensory and visual maps in spatial register [2, 3]. The posterior parietal cortex (PPC) might be critical for such a spatial remapping [4]; nevertheless, a direct causal demonstration of its involvement is lacking. Here, we found that unattended touches to one hand enhanced visual sensitivity for phosphenes induced by occipital trancranial magnetic stimulation (TMS) [5] when the touched hand was spatially coincident to the reported location of the phosphenes in external space. Notably, this spatially specific crossmodal facilitation was maintained after hand crossing, suggesting an efficient visual-tactile remapping. Critically, after 1 Hz repetitive TMS interference [6] over the PPC, but not over the primary somatosensory cortex, phosphene detection was still enhanced by spatially coincident touches with uncrossed hands, but it was enhanced by spatially noncoincident touches after hand crossing. This is the first causal evidence in humans that the PPC constantly updates the representation of the body in space in order to facilitate crossmodal interactions.     

Biologically plausible models of topographic map formation in the somatosensory and auditory cortices

Computational models of the somatosensory and auditory systems have been constructed with the neurosimulator GENESIS. The somatosensory model consists of a cortical layer with 1024 pyramidal cells and 512 basket cells connected to a hand surface with 512 tactile receptors. The auditory model consists of a cortical layer with 2256 pyramidal cells and 1128 basket cells connected to a cochlea with 47 receptors. The models reproduce processes related to the formation and maintenance of somatotopic and tonotopic maps and exhibit several features observed in experiments with animals such as variability in the shapes and sizes of areas of cortical representation and, in the case of somatotopy, cortical magnification values in agreement with experimental findings and linear decay of receptive field overlap as a function of cortical distance between recording sites in normal conditions.     

Saccade-related remapping of target representations between topographic maps: a neural network study

The goal of this study was to explore how a neural network could solve the updating task associated with the double-saccade paradigm, where two targets are flashed in succession and the subject must make saccades to the remembered locations of both targets. Because of the eye rotation of the saccade to the first target, the remembered retinal position of the second target must be updated if an accurate saccade to that target is to be made. We trained a three-layer, feed-forward neural network to solve this updating task using back-propagation. The network's inputs were the initial retinal position of the second target represented by a hill of activation in a 2D topographic array of units, as well as the initial eye orientation and the motor error of the saccade to the first target, each represented as 3D vectors in brainstem coordinates. The output of the network was the updated retinal position of the second target, also represented in a 2D topographic array of units. The network was trained to perform this updating using the full 3D geometry of eye rotations, and was able to produce the updated second-target position to within a 1 degrees RMS accuracy for a set of test points that included saccades of up to 70 degrees . Emergent properties in the network's hidden layer included sigmoidal receptive fields whose orientations formed distinct clusters, and predictive remapping similar to that seen in brain areas associated with saccade generation. Networks with the larger numbers of hidden-layer units developed two distinct types of units with different transformation properties: units that preferentially performed the linear remapping of vector subtraction, and units that performed the nonlinear elements of remapping that arise from initial eye orientation.     

Learning through maps: functional significance of topographic organization in primary sensory cortex.

The presence of "maps" in sensory cortex is a hallmark of the mammalian nervous system, but the functional significance of topographic organization has been called into question by physiological studies claiming that patterns of neural behavioral activity transcend topographic boundaries. This paper discusses recent behavioral and physiological studies suggesting that, when animals or human subjects learn perceptual tasks, the neural modifications associated with the learning are distributed according to the spatial arrangement of the primary sensory cortical map. Topographical cortical representations of sensory events, therefore, appear to constitute a true structural framework for information processing and plasticity.     

Coupling of total hemoglobin concentration,oxygenation, and neural activity in rat somatosensory cortex

Recent advances in brain imaging techniques, including functional magnetic resonance imaging (fMRI), offer great promise for noninvasive mapping of brain function. However, the indirect nature of the imaging signals to the underlying neural activity limits the interpretation of the resulting maps. The present report represents the first systematic study with sufficient statistical power to quantitatively characterize the relationship between changes in blood oxygen content and the neural spiking and synaptic activity. Using two-dimensional optical measurements of hemodynamic signals, simultaneous recordings of neural activity, and an event-related stimulus paradigm, we demonstrate that (1) there is a strongly nonlinear relationship between electrophysiological measures of neuronal activity and the hemodynamic response, (2) the hemodynamic response continues to grow beyond the saturation of electrical activity, and (3) the initial increase in deoxyhemoglobin that precedes an increase in blood volume is counterbalanced by an equal initial decrease in oxyhemoglobin.     

Self-organizing mechanism for the formation of ordered neural mappings

A model for the formation of ordered neural mappings in general, and of retinotectal connections, in particular is given. The main point came from the theory of noise induced transitions, i.e. order may be the result of the interplay between deterministic and random interactions. An activity-dependent self-organizing mechanism is presented in terms of modifiable synapses. Simulation experiments were done not only for the normal ontogenetic development but also for the plastic behaviour of the retinotopic connections.     

Differential effects of aging on fore- and hindpaw maps of rat somatosensory cortex

Getting older is associated with a decline of cognitive and sensorimotor abilities, but it remains elusive whether age-related changes are due to accumulating degenerational processes, rendering them largely irreversible, or whether they reflect plastic, adaptational and presumably compensatory changes. Using aged rats as a model we studied how aging affects neural processing in somatosensory cortex. By multi-unit recordings in the fore- and hindpaw cortical maps we compared the effects of aging on receptive field size and response latencies. While in aged animals response latencies of neurons of both cortical representations were lengthened by approximately the same amount, only RFs of hindpaw neurons showed severe expansion with only little changes of forepaw RFs. To obtain insight into parallel changes of walking behavior, we recorded footprints in young and old animals which revealed a general age-related impairment of walking. In addition we found evidence for a limb-specific deterioration of the hindlimbs that was not observed in the forelimbs. Our results show that age-related changes of somatosensory cortical neurons display a complex pattern of regional specificity and parameter-dependence indicating that aging acts rather selectively on cortical processing of sensory information. The fact that RFs of the fore- and hindpaws do not co-vary in aged animals argues against degenerational processes on a global scale. We therefore conclude that age-related alterations are composed of plastic-adaptive alterations in response to modified use and degenerational changes developing with age. As a consequence, age-related changes need not be irreversible but can be subject to amelioration through training and stimulation.     

Bilateral receptive field neurons and callosal connections in the somatosensory cortex

Earlier studies recording single neuronal activity with bilateral receptive fields in the primary somatosensory cortex of monkeys and cats agreed that the bilateral receptive fields were related exclusively to the body midline and that the ipsilateral information reaches the cortex via callosal connections since they are dense in the cortical region representing the midline structures of the body while practically absent in the regions representing the distal extremities. We recently found a substantial number of neurons with bilateral receptive fields on hand digits, shoulders-arms or legs-feet in the caudalmost part (areas 2 and 5) of the postcentral gyrus in awake Japanese monkeys (Macaca fuscata). I review these results, discuss the functional implications of this bilateral representation in the postcentral somatosensory cortex from a behavioural standpoint and give a new interpretation to the midline fusion theory.     

Experience-induced plasticity of cutaneous maps in the primary somatosensory cortex of adult monkeys and rats

In a first study, the representations of skin surfaces of the hand in the primary somatosensory cortex, area 3b, were reconstructed in owl monkeys and squirrel monkeys trained to pick up food pellets from small, shallow wells, a task which required skilled use of the digits. Training sessions included limited manual exercise over a total period of a few hours of practice. From an early clumsy performance in which many retrieval attempts were required for each successful pellet retrieval, the monkeys exhibited a gradual improvement. Typically, the animals used various combinations of digits before developing a successful retrieval strategy. As the behavior came to be stereotyped, monkeys consistently engaged surfaces of the distal phalanges of one or two digits in the palpation and capture of food pellets from the smallest wells. Microelectrode mapping of the hand surfaces revealed that the glabrous skin of the fingertips predominantly involved in the dexterity task was represented over topographically expanded cortical sectors. Furthermore, cutaneous receptive fields which covered the most frequently stimulated digital tip surfaces were less than half as large as were those representing the corresponding surfaces of control digits. In a second series of experiments, Long-Evans rats were assigned to environments promoting differential tactile experience (standard, enriched, and impoverished) for 80 to 115 days from the time of weaning. A fourth group of young adult rat experienced a severe restriction of forepaw exploratory movement for either 7 or 15 days. Cortical maps derived in the primary somatosensory cortex showed that environmental enrichment induced a substantial enlargement of the cutaneous forepaw representation, and improved its spatial resolution (smaller glabrous receptive fields). In contrast, tactile impoverishment resulted in a degradation of the forepaw representation that was characterized by larger cutaneous receptive fields and the emergence of non-cutaneous responses. Cortical maps derived in the hemispheres contralateral to the immobilized forelimb exhibited a severe decrease of about 50% in the overall areal extent of the cutaneous representation of the forepaw, which resulted from the invasion of topographically organized cortical zones of non-cutaneous responses, and numerous discontinuities in the representation of contiguous skin territories. The size and the spatial arrangement of the cutaneous receptive fields were not significantly modified by the immobilization of the contralateral forelimb. Similar results were obtained regardless of whether the forelimb restriction lasted 7 or 15 days. These two studies corroborate the view that representational constructs are permanently reshaped by novel experiences through dynamic competitive processes. These studies also support the notion that subject-environment interactions play a crucial role in the maintenance of basic organizational features of somatosensory representations.     

ERK is involved in the reorganization of somatosensory cortical maps in adult rats submitted to hindlimb unloading

Sensorimotor restriction by a 14-day period of hindlimb unloading (HU) in the adult rat induces a reorganization of topographic maps and receptive fields. However, the underlying mechanisms are still unclear. Interest was turned towards a possible implication of intracellular MAPK signaling pathway since Extracellular-signal-Regulated Kinase 1/2 (ERK1/2) is known to play a significant role in the control of synaptic plasticity. In order to better understand the mechanisms underlying cortical plasticity in adult rats submitted to a sensorimotor restriction, we analyzed the time-course of ERK1/2 activation by immunoblot and of cortical reorganization by electrophysiological recordings, on rats submitted to hindlimb unloading over four weeks. Immunohistochemistry analysis provided evidence that ERK1/2 phosphorylation was increased in layer III neurons of the somatosensory cortex. This increase was transient, and parallel to the changes in hindpaw cortical map area (layer IV). By contrast, receptive fields were progressively enlarged from 7 to 28 days of hindlimb unloading. To determine whether ERK1/2 was involved in cortical remapping, we administered a specific ERK1/2 inhibitor (PD-98059) through osmotic mini-pump in rats hindlimb unloaded for 14 days. Results demonstrate that focal inhibition of ERK1/2 pathway prevents cortical reorganization, but had no effect on receptive fields. These results suggest that ERK1/2 plays a role in the induction of cortical plasticity during hindlimb unloading.     

A unified model of dominance hierarchy formation and maintenance

In many different species it is common for animals to spend large portions of their lives in groups. Such groups need to divide available resources amongst the individuals they contain and this is often achieved by means of a dominance hierarchy. Sometimes hierarchies are stable over a long period of time and new individuals slot into pre-determined positions, but there are many situations where this is not so and a hierarchy is formed out of a group of individuals meeting for the first time. There are several different models both of the formation of such dominance hierarchies and of already existing hierarchies. These models often treat the two phases as entirely separate, whereas in reality, if there is a genuine formation phase to the hierarchy, behaviour in this phase will be governed by the rewards available, which in turn depends upon how the hierarchy operates once it has been formed. This paper describes a method of unifying models of these two distinct phases, assuming that the hierarchy formed is stable. In particular a framework is introduced which allows a variety of different models of each of the two parts to be used in conjunction with each other, thus enabling a wide range of situations to be modelled. Some examples are given to show how this works in practice.     

Ephrin-as guide the formation of functional maps in the visual cortex

Ephrin-As and their receptors, EphAs, are expressed in the developing cortex where they may act to organize thalamic inputs. Here, we map the visual cortex (V1) in mice deficient for ephrin-A2, -A3, and -A5 functionally, using intrinsic signal optical imaging and microelectrode recording, and structurally, by anatomical tracing of thalamocortical projections. V1 is shifted medially, rotated, and compressed and its internal organization is degraded. Expressing ephrin-A5 ectopically by in utero electroporation in the lateral cortex shifts the map of V1 medially, and expression within V1 disrupts its internal organization. These findings indicate that interactions between gradients of EphA/ephrin-A in the cortex guide map formation, but that factors other than redundant ephrin-As are responsible for the remnant map. Together with earlier work on the retinogeniculate map, the current findings show that the same molecular interactions may operate at successive stages of the visual pathway to organize maps.     

A neural network model of the cerebellar cortex performing dynamic associations

The present paper proposes a model which applies formal neural network modeling techniques to construct a theoretical representation of the cerebellar cortex and its performances in motor control. A schema that makes explicit use of propagation delays of neural signals, is introduced to describe the ability to store temporal sequences of patterns in the Golgi-granule cell system. A perceptron association is then performed on these sequences of patterns by the Purkinje cell layer. The model conforms with important biological constraints, such as the known excitatory or inhibitory nature of the various synapses. Also, as suggested by experimental evidence, the synaptic plasticity underlying the learning ability of the model, is confined to the parallel fiber — Purkinje cell synapses, and takes place under the control of the climbing fibers. The result is a neural network model, constructed according to the anatomy of the cerebellar cortex, and capable of learning and retrieval of temporal sequences of patterns. It provides a framework to represent and interpret properties of learning and control of movements by the cerebellum, and to assess the capacity of formal neural network techniques for modeling of real neural systems.     

A neural network model on self-organizing emergence of simple-cell receptive field with orientation selectivity in visual cortex

In order to probe into the self-organizing emergence of simple cell orientation selectivity, we tried to construct a neural network model that consists of LGN neurons and simple cells in visual cortex and obeys the Hebbian learning rule. We investigated the neural coding and representation of simple cells to a natural image by means of this model. The results show that the structures of their receptive fields are determined by the preferred orientation selectivity of simple cells. However, they are also decided by the emergence of self-organization in the unsupervision learning process. This kind of orientation selectivity results from dynamic self-organization based on the interactions between LGN and cortex.     

A neural network model on self-organizing emergence of simple-cell receptive field with orientation selectivity in visual cortex

In order to probe into the self-organizing emergence of simple cell orientation selectivity, we tried to construct a neural network model that consists of LGN neurons and simple cells in visual cortex and obeys the Hebbian learning rule. We investigated the neural coding and representation of simple cells to a natural image by means of this model. The results show that the structures of their receptive fields are determined by the preferred orientation selectivity of simple cells. However, they are also decided by the emergence of self-organization in the unsupervision learning process. This kind of orientation selectivity results from dynamic self-organization based on the interactions between LGN and cortex.     

Cerebral cortex: the singular precision of visual cortex maps

A remarkable new technique, two-photon confocal fluorescence microscopy, has revealed an extraordinarily precise organization in the visual cortex. The methodology seems set to become the tool of choice for studying cortical maps.     

Sleep contributes to dendritic spine formation and elimination in the developing mouse somatosensory cortex

Sleep is maximal during early postnatal life when rapid and extensive synapse remodeling occurs. It remains unknown whether and how sleep affects synapse development and plasticity. Using transcranial two‐photon microscopy, we examined the formation and elimination of fluorescently labeled dendritic spines and filopodia of Layer 5 pyramidal neurons in the barrel cortex of 3‐week‐old mice during wakefulness and sleep. We observed high turnover of dendritic protrusions over 2 h in both wake and sleep states. The formation rate of dendritic spines or filopodia over 2 h was comparable between the two states. The elimination rate of dendritic spines or filopodia was lower during 2‐h wakefulness than during 2‐h sleep. Similar results were observed on dendritic protrusion dynamics over 12‐h light/dark cycle when mice spent more time asleep or awake. The substantial remodeling of dendritic protrusions during the sleep state supports the notion that sleep plays an important role in the development and plasticity of synaptic connections in the mouse cortex. © 2011 Wiley Periodicals, Inc. Develop Neurobiol, 2012