The development of the retinogeniculate pathway or the geniculocortical pathway, or both, occurs either before birth or before eye opening in many species. It is widely believed that spontaneous retinal activity could drive the segregation of afferents into eye-specific laminae or columns and the refinement of initially diffuse receptive fields and the emergence of orderly, retinotopic organization. We show that a recent computational model that generates a phenomenologically accurate representation of spontaneous retinal activity can indeed drive afferent segregation and, more particularly, topographic and receptive field refinement in the retinogeniculocortical system. We use a model of anatomical synaptic plasticity based on recent data suggesting that afferents might compete for limited amounts of retrograde neurotrophic factors (NTFs). We find that afferent segregation and receptive field formation are disrupted in the

In the primary visual cortex of strabismic cats, the elimination of correlated activity between the two eyes enhances the segregation of the geniculocortical afferents into alternating ocular dominance domains. In addition, both tangential intracortical fibres and neuronal synchronization are severely reduced between neurons activated by different eyes. Consequently, ocular dominance columns belonging to different eyes are functionally rather independent. We wondered whether this would also affect the organization of orientation preference maps. To this end, we visualized the functional architecture of area 17 of strabismic cats with both optical imaging based on intrinsic signals and double labelling of orientation and ocular dominance columns with [ 14 C]2-deoxyglucose and [ 3 H]proline. As expected, monocular iso-orientation domains had a patchy appearance and differed for the two eyes, leading to a clear segregation of the ocular dominance domains. Comparison of ‘angle maps ’ revealed that orientation domains exhibit a pinwheel organization as in normally reared cats. Interestingly, the map of orientation preferences did not show any breaks at the borders between ocular dominance columns: iso-orientation domains were continuous across these borders. In addition, iso-orientation contours tended to cross the borders of adjacent ocular dominance columns at right angles. These data suggest that the basic relations between the layout of orientation maps and ocular dominance columns are not disturbed by artificial decorrelation of binocular input. Therefore in cat area 17, the orientation map does not seem to be modified by experience-dependent changes of thalamic input connections. This suggests the possibility that usedependent rearrangement of geniculocortical afferents into ocular dominance columns is due to Hebbian modifications whereby postsynaptic responsivity is constrained by the scaffold of the orientation map.

The expression of development programmes encoded in genes leads to the wide range of structures and functionality found in biology. Neural development is a highly adaptive form of selforganisation. This arises from the ability of neural systems to fine-tune their structure to both internal and external environments after an initial over-production of neural elements. Such structural refinement is a necessary part of selforganisation. This paper reports a biologically motivated model that regulates and refines the growth of neuron-to-neuron interconnections in a 3D artificial neural network. Our inspiration is spontaneous neural activity and the multiple roles of neurotrophic factors in biological systems. The model implements self-regulating growth of neurons, and competitive mechanisms which remove complete neuronal trees and differentiate between individual synapses. 1 Developmental Self-Organisation and Artificial Evolution The rich variety of neural systems seen in nature are pro...

activity. Between postnatal day 1 (P1) and P10 in this species, spontaneous activity is mediated by nicotinic cholinergic transmission (Feller et al., 1996; Penn et al., 1998) and, in the form of either action potential firing (Meister et al., 1991) or transient influxes of calcium (e.g., United Kingdom Feller et al., 1996), takes the form of waves that sweep 2Institut Pasteur CNRS URA 2182 periodically across the retina. Although calcium tran-“Récepteurs et Cognition ” sients and action potentials are well correlated in normal Departement des Biotechnologies retinae (Feller et al., 1996), they can be differentially Institut Pasteur affected by certain experimental manipulations (Huber-25 Rue du Docteur Roux man et al., 2003). For this reason, we will henceforth use 75724 Paris Cedex 15 the term “retinal waves ” to refer only to activity assessed

During visual system development, the light-insensitive retina spontaneously generates waves of activity, which are transmitted to the lateral geniculate nucleus. The crucial question is whether retinal waves are further transmitted to the cortex and influence the early cortical patterns of activity. Using simultaneous recordings from the rat retina and visual cortex during the first postnatal week in vivo, we found that spontaneous retinal bursts are correlated with spindle bursts (intermittent network bursts associated with spindle-shape field oscillations) in the contralateral visual cortex (V1). V1 spindle bursts could be evoked by electrical stimulation of the optic nerve. Intraocular injection of forskolin, which augments retinal waves, increased the occurrence of V1 spindle bursts. Blocking propagation of retinal activity, or removal of the retina reduced the frequency, but did not completely eliminate the cortical spindle bursts. These results indicate that spontaneous retinal waves are transmitted to the visual cortex and trigger endogenous spindle bursts. We propose that the interaction between retinal waves and spindle bursts contributes to the development of visual pathways to the cortex. Key words: development; in vivo; delta brush; oscillations; forskolin; patch clamp

Neural activity is often required for the final stages of synaptic refinement during brain development. It is thought that learning rules acting at the individual synapse level, which specify how pre- and postsynaptic activity lead to changes in synaptic efficacy, underlie such activity-dependent development. How such rules might function in vivo can be addressed in the retinogeniculate system because the input activity from the retina and its importance in development are both known. In fact, detailed studies of retinal waves have revealed their complex spatiotemporal properties, providing insights into the mechanisms that use such activity to guide development. First of all, the information useful for development is contained in the retinal waves and can be quantified, placing constraints on synaptic learning rules that use this information. Furthermore, knowing the distribution of activity over the entire set of inputs makes it possible to address a necessary component of developmental refinement: rules governing competition between synaptic inputs. In this way, the detailed knowledge of retinal input and lateral geniculate nucleus development provides a unique opportunity to relate the rules of synaptic plasticity directly to their role in development. NEUROSCIENTIST 8(3):243–253, 2002

During the development of the mammalian retinocollicular projection, a coarse retinotopic map is set up by the graded distribution of axon guidance molecules. Subsequent refinement of the initially diffuse projection has been shown to depend on the spatially correlated firing of retinal ganglion cells. In this scheme, the abolition of patterned retinal activity is not expected to influence overall retinotopic organization, but this has not been investigated. We used optical imaging of intrinsic signals to visualize the complete retinotopic map in the superior colliculus (SC) of mice lacking early retinal waves, caused by the deletion of the �2 subunit of the nicotinic acetylcholine receptor. As expected from previous anatomical studies in the SC of �2 �/ � mice, regions activated by individual visual stimuli were much larger and had less sharp borders than those in wild-type mice. Importantly, however, we also found systematic distortions of the entire retinotopic map: the map of visual space was expanded anteriorly and compressed posteriorly. Thus, patterned neuronal activity in the early retina has a substantial influence on the coarse retinotopic organization of the SC. Key words: superior colliculus; retinal waves; retinotopic map; activity-dependent refinement; intrinsic signal imaging; �2 subunit of nicotinic acetylcholine receptor

ABSTRACT: In the developing vertebrate retina, nAChR synapses are among the first to appear. This early cholinergic circuitry plays a key role in generating “retinal waves, ” spontaneously generated waves of action potentials that sweep across the ganglion cell layer. These retinal waves exist for a short period of time during development when several circuits within the visual system are being established. Here I review the

Copyright © 2007 by the American Physiological Society. The relay of information at the retinogeniculate synapse, the connection between retina and visual thalamus, begins days before eye opening, and is thought to play an important role in the maturation of neural circuits in the thalamus and visual cortex. Remarkably, during this period of development, the retinogeniculate synapse is immature, with single retinal ganglion cell inputs evoking an average peak excitatory postsynaptic current (EPSC) of only ~40 pA when compared to 800 pA in mature synapses. Yet, at the mature synapse, EPSCs greater than 400 pA are needed to drive relay neuron firing. This raises the question of how small amplitude EPSCs can drive transmission at the immature retinogeniculate synapse. Here we find that several features of the immature synapse, when compared to the mature synapse, contribute to synaptic transmission. First, although the peak amplitude of EPSC is small, the decay time course of both AMPA and NMDA receptor (NMDAR) currents is significantly slower. The prolonged time course of NMDAR currents is a result of the presence of NR2B as well as NR2C/D subunits. In addition, extended presence of neurotransmitter released prolongs the synaptic current time course. Second, reduced sensitivity to magnesium block results in significantly greater synaptic charge transfer through NMDAR. Third, AMPAR currents contribute to the spike latency, but not to temporal precision at the immature synapse. Furthermore, intrinsic excitability is greater. These properties enable immature synapses with predominantly NMDAR and little or no AMPAR to contribute to the relay of information from retina to visual cortex.

stages of visual processing, where most is known about