Synapse elimination and learning rules co-regulated by MHC class I H2-Db.

The formation of precise connections between retina and lateral geniculate nucleus (LGN) involves the activity-dependent elimination of some synapses, with strengthening and retention of others. Here we show that the major histocompatibility complex (MHC) class I molecule H2-D(b) is necessary and sufficient for synapse elimination in the retinogeniculate system. In mice lacking both H2-K(b) and H2-D(b) (K(b)D(b)(-/-)), despite intact retinal activity and basal synaptic transmission, the developmentally regulated decrease in functional convergence of retinal ganglion cell synaptic inputs to LGN neurons fails and eye-specific layers do not form. Neuronal expression of just H2-D(b) in K(b)D(b)(-/-) mice rescues both synapse elimination and eye-specific segregation despite a compromised immune system. When patterns of stimulation mimicking endogenous retinal waves are used to probe synaptic learning rules at retinogeniculate synapses, long-term potentiation (LTP) is intact but long-term depression (LTD) is impaired in K(b)D(b)(-/-) mice. This change is due to an increase in Ca(2+)-permeable AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptors. Restoring H2-D(b) to K(b)D(b)(-/-) neurons renders AMPA receptors Ca(2+) impermeable and rescues LTD. These observations reveal an MHC-class-I-mediated link between developmental synapse pruning and balanced synaptic learning rules enabling both LTD and LTP, and demonstrate a direct requirement for H2-D(b) in functional and structural synapse pruning in CNS neurons

A Burst-Based “Hebbian” Learning Rule at Retinogeniculate Synapses Links Retinal Waves to Activity-Dependent Refinement

Patterned spontaneous activity in the developing retina is necessary to drive synaptic refinement in the lateral geniculate nucleus (LGN). Using perforated patch recordings from neurons in LGN slices during the period of eye segregation, we examine how such burst-based activity can instruct this refinement. Retinogeniculate synapses have a novel learning rule that depends on the latencies between pre- and postsynaptic bursts on the order of one second: coincident bursts produce long-lasting synaptic enhancement, whereas non-overlapping bursts produce mild synaptic weakening. It is consistent with “Hebbian” development thought to exist at this synapse, and we demonstrate computationally that such a rule can robustly use retinal waves to drive eye segregation and retinotopic refinement. Thus, by measuring plasticity induced by natural activity patterns, synaptic learning rules can be linked directly to their larger role in instructing the patterning of neural connectivity

Interaction dynamique entre inné et acquis dans le câblage neuronal du cerveau

Pr Carla Shatz © P. Imbert, Collège de France Dans cette série de trois conférences, le Pr Carla J. Shatz a envisagé comment l’activité neurale, d’abord spontanée, puis issue de la stimulation sensorielle, contribue à l’élaboration et l’optimisation des circuits neuronaux pendant les périodes critiques du développement cérébral. Ces conférences ont porté sur le développement du système visuel des mammifères, et plus particulièrement sur les connexions entre la rétine, le corps genouillé latér..

Dynamic Interplay between Nature and Nurture in Brain Wiring

In this series of three lectures, I consider examples of how neural activity, initially spontaneously-generated and at later ages driven by sensory experience, contributes to the shaping and tuning of neural circuits during critical periods of brain development. The lectures focus on the development of the mammalian visual system and specifically consider the connections from retina to lateral geniculate nucleus to primary visual cortex. These connections begin to form early in life in utero ..

Effects of Experience on Visual System Wiring

Neural connections in the adult central nervous system are highly precise. In the visual system, retinal ganglion cells send their axons to target neurons in the LGN in such a way that axons originating from the two eyes terminate in adjacent but non-overlapping eye-specific layers

Frontiers in Visual Cotext Development

During the development of the visual system of higher mammals, axons from the lateral geniculate nucleus (LGN) become segregated into eye-specific patches (the ocular dominance columns) within their target, layer 4 of the primary visual cortex. This occurs as a consequence of activity-dependent synaptic competition between axons representing the two eyes

The Subplate, A Transient Neocortical Structure: Its Role in the Development of Connections between Thalamus and Cortex

The functioning of the mammalian brain depends upon the precision and accuracy of its neural connections, and nowhere is this requirement more evident than in the neocortex of the cerebral hemispheres. The neocortex is a structure that is divided both radially, from the pial surface to the white matter into six cell layers, and tangentially into more than 40 different cytoarchitectural areas (Brodmann 1909). For instance, within the cerebral hemispheres, sets of tangential axonal connections link neurons within a given cortical layer to each other and also link neurons of different cortical areas; sets of radial connections link neurons of different layers together. In addition, the major input to the neocortex arises from neurons in the thalamus, which in tum receive a reciprocal set of connections from the cortex. These connections are highly restricted: In the radial domain, thalamic axons make their major projection to the neurons of cortical layer 4, and the neurons of cortical layer 6 project back to the thalamus. Connections are also restricted tangentially, in that neurons located in specific subdivisions of the thalamus send their axons to specific cortical areas. For instance, neurons in the lateral geniculate nucleus (LGN) of the thalamus connect with primary visual cortex, whereas those situated in the ventrobasal complex connect with somatosensory cortex. There are also local patterns of connections within a given cortical area, for example, the ocular dominance columns in primary visual cortex of higher mammals, or the barrels in rodent somatosensory cortex (Woolsey & van der Loos 1970). The ocular dominance columns are based on the fact that the inputs of LGN axons representing the two eyes are segregated from each other in layer 4 and their terminal arbors are clustered together in patches (LeVay et al 1980). A primary question is how these sets of connections form during development. The purpose of this review is to consider this question as it pertains specifically to the formation of connections between thalamus and cortex [for a more general review of the formation of connectivity, see Goodman & Shatz (1993)]. Several major steps are involved in this developmental process. First, the constituent neurons of the thalamus and cortex must be generated. Next, axons must grow along the appropriate pathways and select the appropriate targets. In the visual system, this means that LGN axons must grow up through the internal capsule, bypass many other inappropriate cortical areas, and then select visual cortex. Finally, the axons must enter the cortical plate, recognize and terminate within layer 4, and segregate to form ocular dominance columns. Thus, in addition to the general problems of pathfinding and target selection faced by all developing neurons, thalamic neurons are faced with a series of tangential and radial decisions as they form the final pattern of connections within neocortex: they must choose the correct cortical area and the correct layer, and must restrict the extent of their terminal arbors. In addition, similar problems must be solved by the neurons of cortical layer 6 as they grow towards and invade their thalamic targets. A growing body of evidence suggests that the formation of connections between thalamus and cortex requires the presence of a specific and transient cell type, subplate neurons. These neurons are present early in development, but by adulthood the majority have disappeared. Here we consider their life history and review the evidence for their role in the patterning of connections

Activity-Dependent Cortical Target Selection by Thalamic Axons

Connections in the developing nervous system are thought to be formed initially by an activity-independent process of axon pathfinding and target selection and subsequently refined by neural activity. Blockade of sodium action potentials by intracranial infusion of tetrodotoxin in cats during the early period when axons from the lateral geniculate nucleus (LGN) were in the process of selecting visual cortex as their target altered the pattern and precision of this thalamocortical projection. The majority of LGN neurons, rather than projecting to visual cortex, elaborated a significant projection within the subplate of cortical areas normally bypassed. Those axons that did project to their correct target were topographically disorganized. Thus, neural activity is required for initial targeting decisions made by thalamic axons as they traverse the subplate