In all parts of the CNS such early patterns of growth by pioneer axons, controlled by chemical morphogens, lay down a basic scaffold of axon tracts that can be followed by later axons and in this way help to direct their growth. They then turn to grow longitudinally, either towards the head or the tail, or they branch to grow in both directions. After crossing, these axons are transformed and no longer attracted to the ventral floor plate. For example, the Shh gradient can attract some axons to grow ventrally and cross to the opposite side. Remarkably, the same morphogen gradients that control cell fates can also influence axon growth. The factors controlling the directions of outgrowth are beginning to be revealed. Once a cell has acquired a specific neuronal fate, the next step is to grow an axon from the neuron soma.
#DENDRITE FUNCTION DETAILED SERIES#
These initially control the fate of differentiating neurons to establish a dorso-ventral series of longitudinal columns of distinct neurons on each side (Figure 1c). The vertebrate spinal cord provides a simple example where chemical morphogens released from the dorsal roof plate (bone morphogenetic protein) and ventral floor plate (sonic hedgehog (Shh)) form dorso-ventral molecular gradients. At the core of this, what are the rules that ensure that appropriate and specific synaptic connections are made as neuronal circuits develop? This is one of the most intensively studied areas of developmental neuroscience and has generated an extensive body of knowledge on the chemical cues that control the assembly of neuronal circuits in the central nervous system (CNS). This specificity is achieved during development by many mechanisms, for example, correct neuronal specification and differentiation, axon path finding, cell recognition and synapse conditioning by neuronal activities. To function properly, nervous systems rely on highly specific synaptic connections between neurons. Our analysis implies that detailed cellular recognition between spinal neuron types may not be necessary for the reliable formation of functional networks to generate early behaviour like swimming. Simple factors such as morphogen gradients controlling dorso-ventral soma, dendrite and axon positions may sufficiently constrain the synaptic connections made between different types of neuron as the spinal cord first develops and allow functional networks to form. A majority of these networks produced robust swimming activity. To test if probabilistic rules could produce functioning spinal networks, we then made realistic computational models of spinal cord neurons, giving them established cell-specific properties and connecting them into networks using the contact probabilities we had determined. To test the plausibility of simpler hypotheses, we first made computational models that were able to generate longitudinal axon growth paths and reproduce the axon distribution patterns and synaptic contact probabilities found in the spinal cord. These results suggested that synapse formation may not require axons to recognise specific, correct dendrites. Surprisingly, synapses were found between all types of neuron but contact probabilities could be predicted simply by the anatomical overlap of their axons and dendrites. For the same neuron types, the dorso-ventral distributions of axons and dendrites were measured and then used to calculate the probabilities that axons would encounter particular dendrites and so potentially form synaptic connections. The probabilities of synapses between 7 types of identified spinal neuron were measured directly by making electrical recordings from 500 pairs of neurons. This is possible because detailed information is now available on the identity and synaptic connections of the main types of neuron. How specific are the synaptic connections formed as neuronal networks develop and can simple rules account for the formation of functioning circuits? These questions are assessed in the spinal circuits controlling swimming in hatchling frog tadpoles.
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