Interesting paper by Knafo et al from a couple of months ago that I’ve been meaning to talk about. This group previously made a synthetic peptide (called FGL) that mimics the active site of a cell adhesion molecule involved in neurite outgrowth (NCAM).
When they subcutaneously inject some amount of this molecule into rats, they learn to navigate a water maze faster. So, cognitive enhancement. Not bad.
Down to mechanism. They fix rat hippocampal sections and investigate a variety of neural morphology measures. No significant differences, although the synapse density looks pretty close to significance to me.
Instead, it seems like this peptide is exerting its effects by recruiting more AMPA receptors to the postsynaptic densities of excitatory CA1 cells. Probably their strongest evidence for this is that, in hippocampal slice cultures, more GFP-tagged AMPA receptors are delivered to the synapse 24-36 hrs after the addition of the peptide.
So this is an example where neural connectivity, by itself, seems quite unable to explain all the physiology and behavior in their experiments. Of course, it’s possible that concomitant with the functional (but not structural) changes in the hippocampus, there are correlated structural (but not functional) changes elsewhere in the rat’s brain. But that seems less parsimonious.
Knafo S, Venero C, Sánchez-Puelles C, Pereda-Peréz I, Franco A, et al. (2012) Facilitation of AMPA Receptor Synaptic Delivery as a Molecular Mechanism for Cognitive Enhancement. PLoS Biol 10(2): e1001262. doi:10.1371/journal.pbio.1001262