Aging / Learning and Memory / Neuro News

Keeping Memories Fresh by Keeping Glutamate In Check

We are another year older, perhaps a little wiser, and probably more forgetful.  Indeed, making memories is quite a process in the brain: specific synaptic connections are strengthened and new proteins are synthesized.  But as we age, the synapses that make up our memories, such as those in the hippocampus and prefrontal cortex, start to change and can be lost altogether.  The detrimental synaptic alterations may not be permanent, however, and maintaining the health of these synapses may be the key to preventing age-related cognitive decline.

Dendritic Spines Knowing Neurons

Dendritic spines are the site of synaptic transmission. Confocal image courtesy Hanke Heun-Johnson.

A research team from The Rockefeller University examined this hypothesis by studying memory loss in aging rats.  They focused on glutamatergic neuronal circuits because those synapses are most vulnerable to aging and make connections between associated cortical areas as well as the hippocampus.  Synaptic glutamatergic activity is neuroprotective and essential for memory formation via long-term potentiation (LTP), a long-lasting increase in synaptic strength, but extrasynaptic glutamatergic activity (i.e. when there is too much glutamate and it spills out of the synapse) causes long-term depression (LTD).  Recent studies have shown that with age, there is a decrease in glutamate uptake by glia, which leads to glutamate spillover into the extrasynaptic space and possibly cognitive decline.  Thus, the team sought to use glutamate modulators as a therapeutic target in regulating synaptic age-related glutamatergic dysregulation.

The team chose to investigate a drug called riluzole, which increases glutamate uptake by glia, thus preventing glutamate overflow.  Once a rat became middle-aged (about 10 months), it was given regular doses of riluzole for 17 weeks.  These rats were better able to perform hippocampus-dependent spatial memory tasks than untreated rats.  For instance, when treated rats were placed in an environment and recognized there was something new in there, they spent more time investigating that novel space, while untreated rats did not notice any changes in their environment.

Importantly, this memory performance correlated with dendritic spine density on neurons in the hippocampus and prefrontal cortex, brain regions that have age-related spine loss.  The clustering of dendritic spines is an essential neuroplastic mechanism and is a measure of the strength of neural circuits.  In particular, the clusters mostly affected thin spines, a rapidly adaptable type of spine.  So, how might dendritic spines change during aging?  This schematic explains:

Dendritic Spin Aging Knowing Neurons

These results suggest that this clustering phenomenon may be the key mechanism to prevent age-related cognitive decline.  By compensating for the changes at glutamatergic synapses by changing glutamate levels, it may even be possible to protect against Alzheimer’s disease-related dementia.  Indeed future studies will show effective riluzole and other glutamate modulators are at preserving the cognitive function of the aging human brain.

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References:

Images from Hanke Heun-Johnson and made by Jooyeun Lee.

Pereira A.C., Yael S. Grossman, Dani Dumitriu, Rachel Waldman, Sophia K. Jannetty, Katina Calakos, William G. Janssen, Bruce S. McEwen & John H. Morrison (2014). Glutamatergic regulation prevents hippocampal-dependent age-related cognitive decline through dendritic spine clustering, Proceedings of the National Academy of Sciences, 111 (52) 18733-18738. DOI: http://dx.doi.org/10.1073/pnas.1421285111

One thought on “Keeping Memories Fresh by Keeping Glutamate In Check

  1. Pingback: Our Year in Neuroscience | Knowing Neurons

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