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New Steps Discovered in Synapse Building and Pruning Print E-mail
SciMed - Neuroscience
TS-Si News Service   
Thursday, 17 November 2011 16:00
Glutamatergic synapse.Bar Harbor, ME, USA. Researchers have discovered a new factor in synapse-building, also showing that the building and pruning processes occur independently of each other.

Like a gardener who stakes some plants and weeds out others, the brain is constantly building networks of synapses, while pruning out redundant or unneeded synapses.


Mammals are born with functioning but not-yet-developed brains. After birth, external stimuli and internal programs continue to shape the connections between neurons, known as synapses, and the formation of networks of synapses known as neuronal circuits. Some grow stronger, some grow weaker, redundant connections are eliminated, and so on.

Zhong-wei Zhang, Ph.D.

Zhong-wei Zhang, Ph.D. is an Assistant Staff Scientist at The Jackson Laboratory, an independent, nonprofit organization focusing on mammalian genetics research to advance human health.
Plasticity, the ongoing refinement of neural connections and networks, continues throughout life, albeit more subtly with time and maturation. Much about it remains unknown. How the neural circuits are modified, what controls the modification, the mechanics of strengthening or eliminating specific synapses and much more are subjects of ongoing research.

Besides gaining a better picture of normal brain development, scientists seek to understand the errors in synapse building and pruning that are associated with autism, mental retardation and schizophrenia. Assistant Professor Zhong-wei Zhang, Ph.D., at The Jackson Laboratory, and his colleagues investigated a major type of synapse in the brain (called the glutamatergic synapse) that undergoes rapid refinement soon after birth.

Their findings appear in the Journal of Neuroscience. The synapses are strengthened through the addition of a particular kind of glutamate receptors, beginning about a week after birth for mice. Notably, sensory deprivation disrupts synapse strengthening, highlighting the role of early experience in synapse building.

In a somewhat surprising finding, the Zhang lab also discovered that the elimination of redundant synapses was not dependent on the other synapses' being strengthened. Since synaptic strengthening usually precedes removal of redundant synapses, it was not known if such elimination is dependent on the prior strengthening.

In mice lacking the receptor, which prevented significant strengthening of synaptic connections, redundant synapses were eliminated as usual.

CitationRedundant Synaptic Inputs in the Absence of Synaptic Strengthening. Hao Wang, Hong Liu, Zhong-Wei Zhang. Journal of Neuroscience 2011; 31(46): 16675-16684. doi:10.1523/JNEUROSCI.4569-11.2011

Abstract

Synaptic refinement, a developmental process that consists of selective elimination and strengthening of immature synapses, is essential for the formation of precise neuronal circuits and proper brain function. At glutamatergic synapses in the brain, activity-dependent recruitment of AMPA receptors (AMPARs) is a key mechanism underlying the strengthening of immature synapses. Studies using receptor overexpression have shown that the recruitment of AMPARs is subunit specific. With the notable exception of hippocampal CA3–CA1 synapses, however, little is known about how native receptors behave or the roles of specific AMPAR subunits in synaptic refinement in vivo. Using patch-clamp recordings in acute slices, we examined developmental refinement of whisker relay (lemniscal) synapses in the thalamus in mice deficient of AMPAR subunits. Deletion of GluA3 or GluA4 caused significant reductions of synaptic AMPAR currents in thalamic neurons at P16–P17, with a greater reduction observed in GluA3-deficient mice. Deletions of both GluA3 and GluA4 abolished synaptic AMPAR responses in the majority of thalamic neurons, indicating that at thalamic relay synapses AMPARs are composed primarily of GluA3 and GluA4. Surprisingly, deletions of GluA3 or GluA4 or both had no effect on the elimination of relay inputs: the majority of thalamic neurons in these knock-out mice—as in wild-type mice—receive a single relay input. However, experience-dependent strengthening of thalamic relay synapses was impaired in GluA3 knock-out mice. Together these findings suggest that the elimination of immature glutamatergic synapses proceeds normally in the absence of synaptic strengthening, and highlight the role of GluA3-containing AMPARs in experience-dependent synaptic plasticity.

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Last Updated on Thursday, 17 November 2011 12:06