Plasticity states:

  • Valproic acid is believed to have multiple pharmacological actions, including acute blockade of GABA transaminase to enhance inhibitory function in epileptic seizures and enduring effects on gene transcription as an histone deacetlyase (HDAC) inhibitor (Monti et al., 2009). Of relevance here is the epigenetic actions of this drug, as enhancing inhibition does not reactivate brain plasticity in adulthood (Fagiolini and Hensch, 2000), but reopening chromatin structure does (Putignano et al., 2007). While systemic drug application is a rather coarse treatment, the effects may differ dramatically by individual cell type (TK Hensch and P Carninci, unpublished observations). VPA treatment mimics Nogo receptor deletion to reopen plasticity for acoustic preference in mice (Yang et al., 2012), suggesting a common pathway through the regulation of myelin-related signaling which normally closes critical period plasticity (McGee et al., 2005).

This says Valproate does two completely separate things:

  1. lowers neuron firing rate by blocking GABA transaminase, thus increasing GABA levels
  2. works as an HDAC inhibitor

And that the latter increases plasticity.
It says that it has the same effect as Nogo receptor deletion.

It suggests both Nogo receptor deletion and VPA both regulate myelin-related signaling (which normally closes critical period plasticity).

It seems to be suggesting that it is not known how VPA accomplishes this.

The paper continues:

  • Future work will address the cellular actions of VPA treatment in the process of reactivating critical periods. Future MRI studies will also be needed to establish whether HDAC inhibition by VPA induces hyperconnectivity of myelinated, long-range connections concurrent with renewed AP ability (Loui et al., 2011).

That last paper: <— BIG AP Paper!




T K Hensch <— all round introduction to critical period and methods of extending it <— Synapse stuff, ALevel/Degree <— hearing pathways <— GOOD cellular respiration <— HUNDREDS! <— Growth Cones! 12 min

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