"In summary, Ehlers and colleagues (Lee et al., 2010) use infection of a tetanus toxin light chain to silence isolated synapses and uncaging of glutamate at single spines to reveal priming of individual synapses for LTP. The authors show that the underlying molecular mechanism involves an increase in NMDA receptor number and a switch in NMDA receptor phenotype from NR2A-containing to NR2B-containing receptors. Alterations in postsynaptic NMDA receptors are associated with an increase in postsynaptic Ca2+ and increase in the NMDA component of the EPSC. These findings are significant in that they show for the first time that metaplasticity, once thought to be a process involving a global change in the biophysical properties of entire neural networks, can occur within a single synapse. Understanding how changes in NMDA receptor number and subtype alter the threshold for potentiation is likely to cast light on the molecular mechanisms involved in plasticity and priming in general and increase our understanding of how neural networks participate in higher cognitive function, including learning and memory, and how their dysregulation causes neuropsychiatric disorders, including autism."
Synapse-Specific Metaplasticity: To Be Silenced is Not to be Silenced 2B
The emphasis in this article, and the Lee et al study it previews, is on plasticity changes in single synapses. This humble father of a son with Autistic Disorder does not pretend to have the knowledge of the subject matter or the jargon to follow the logic of the discussion without a great deal of effort and research. I do find it interesting to note how some of the concepts of which I have some degree of understanding are almost casually mentioned as factual. Autism is clearly identified as being caused by dysregulation of neural networks in a very unqualified manner. It is also interesting how the neural networks are described as participating in higher cognitive functions ... making a clear association between dysregulated cognitive functions and autism.
It is refreshing to see autism discussed objectively as a synaptic disorder.involving cognitive challenges, not glorified or misrepresented. Hopefully our increasing understanding of the synaptic bases and functions involved in autism disorders will some day result in treatments to help autistic persons who want to overcome their disorders and the families who seek treatment for their children affected by autism disorders.
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