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Updated 14 March 2010
Printable version

Forum Discussion: Functional and Dysfunctional Synaptic Plasticity in Prefrontal Cortex

In our Forum Discussion "journal club" series, the editors of some of the journals in the field provide open access to the full text of a recent article. In this case, we thank the Society for Biological Psychiatry, not to mention Elsevier Journals, for providing access for six months to an article in Biological Psychiatry. A short introduction by a journal editor gets us started, and then it's up to our readers to share their ideas and insights, questions, and reactions to the selected paper. So read on....

Goto Y, Yang CR, Otani S. Functional and dysfunctional synaptic plasticity in prefrontal cortex: roles in psychiatric disorders. Biol Psychiatry. 2010 Feb 1; 67(3):199-207. Abstract

View the full text of the article.

View Comments By:
Brian Morris — Posted 25 March 2010

Background Text
By Paul Harrison, University of Oxford

Synaptic plasticity has become embedded in, and is increasingly central to, contemporary explanatory models of brain function. It is equally prominent in models of the pathophysiological basis of most psychiatric disorders including schizophrenia, addiction, mood disorder, and Alzheimer’s disease. Goto, Yang, and Otani provide a valuable, elegant, and concise review (complemented by extensive supplementary online material for aficionados) of synaptic plasticity in the prefrontal cortex (PFC). It is a perfect starting point for those wanting to get into this fast-moving and fascinating field.

Goto and colleagues note the relative neglect of the PFC compared to the hippocampus with regard to synaptic plasticity. They summarize diverse evidence which shows—strikingly, though perhaps not surprisingly—that the PFC indeed possesses the capability and machinery for various forms of synaptic plasticity, albeit using molecules and mechanisms that likely differ, at least in part, from those in the hippocampus. Another focus of the review is the key role that dopamine plays in the modulation of PFC synaptic plasticity, including the balance of D1 versus D2 receptor activation, and the direct and indirect interactions of dopamine with other transmitter systems, notably glutamate (via N-methyl-D-aspartate receptors and group II metabotropic receptors). Finally, Goto and colleagues briefly introduce the ways in which dopamine-mediated PFC synaptic plasticity may go awry in psychiatric disorders, and its candidacy as a cellular mechanism for therapeutic remediation.

Any topic as complex, multifaceted, and in places controversial, as this one raises many areas for discussion. Readers will have their favorite (suggestions, please!), but to get a debate going, how about the following?

1. What are the known similarities and differences between the mechanisms of PFC synaptic plasticity and those in the hippocampus? Similarly, what is the extent of intra-PFC heterogeneity (e.g., ventral versus dorsal)?

2. How readily should we extrapolate from mechanisms (and terminologies) studied in experimental animal models to humans? For example, to what extent is “long-term- potentiation-like facilitation” (elicited in humans using paired-associate stimulation or transcranial direct current stimulation) the same as classical long-term potentiation (defined based on electrophysiological recordings)? Can we know? Does it matter at this stage?

3. As the authors note, several neuromodulators other than dopamine are also involved in PFC synaptic plasticity. Do we yet know the relative roles of, and interactions between, these various modulators? Can a molecular dissection be made in terms of their contributions to different components or mechanisms of plasticity, or to different neural circuits, synaptic populations, or developmental stages? Or to any other categorization or dimension of plasticity?

4. How can current notions and theories of PFC synaptic plasticity be made more specific? Are there refutable hypotheses about its nature, location, or functional significance that can help take us forward?

Comments on Online Discussion
Comment by:  Brian Morris
Submitted 25 March 2010 Posted 25 March 2010

This is an important and developing area, and this review...  Read more

View all comments by Brian Morris
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