Kurzweil Intelligence reports, a Yale study just published today in Nature, on How aging affects working-memory neuron firing rate and how to improve it Researches have found that the "neural networks in the brains of the middle-aged and elderly have weaker connections and fire less robustly than in youthful ones," due to accumulations of higher levels of a neurochemical called cAMP.
Average activity for the brain networks that subserve working memory (credit: Min Wan et al./Nature)
“With normal aging, there are impairments in the working memory functions of the prefrontal cortex (PFC),” says Amy F. T. Arnsten, professor or neurobiology at Yale University Medical School. “The prefrontal cortex is the most evolved part of the brain, located just behind our forehead. It is our mental sketchpad, a process called working memory … essential for executive functions, allowing us to overcome distractions and interference, and helping us to multitask.”
The researchers studied the firing of PFC neurons in young, middle-aged, and old animals as they performed a working-memory task. Neurons in the prefrontal cortex of the young animals were able to maintain firing at a high rate during working memory, while neurons in older animals showed slower firing rates.
The aging prefrontal cortex appears to accumulate excessive levels of a signaling molecule called cAMP, which can open ion channels and weaken prefrontal neuronal firing, especially under stress, or from lack of sleep, poor nutrition, and other factors.
But, wait, don't despair. Researchers already know how to reduce cAMP, in monkeys and humans, with a medication already on the market, called guanfacine. And, from what I can tell from the abstract, and Kurweil Intelligence reports, the researchers used it in monkeys to restore youthful firing rates as part of this experiment.
A medication called guanfacine, already approved for hypertension, and ADD in young people is known to reduce cAMP, so the researchers used it to restore youthful brain firing patterns in monkeys, and has lead researchers to start an immediate study to see if this can return the neural firing rates, in the pre-frontal cortex of the middle aged, and elderly back to youthful levels in humans.
(Credit: Yale University Medical School)
From the
abstractin Nature:
Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.
The way they "adjusted' the neurochemical environment blocked HCN and KCNQ channels, were with guanfacine. You'll have to go to Kurweil Intelligence to read their full article to get the details.
But, the usual suspects of stress, lack of sleep, and poor nutrition can cause even young-people to experience short-term increases in cAMP.
I predict it will also create a rush of elderly folks rushing to their doctors tomorrow, for prescriptions. That's my plan. I'll let you know how crowded it is, as long as I don't forget this promise.
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Footnote: For those of you who enjoy original scientific sources here is a link to the abstract and opportunity to read the entire article if you wish to pay $32.
Ref.: Min Wang, et al., Neuronal basis of age-related working memory decline, Nature, 2011; [DOI: 10.1038/nature10243]
http://www.nature.com/...
Neuronal basis of age-related working memory decline
Min Wang,
Nao J. Gamo,
Yang Yang,
Lu E. Jin,
Xiao-Jing Wang,
Mark Laubach,
James A. Mazer,
Daeyeol Lee
& Amy F. T. Arnsten
Many of the cognitive deficits of normal ageing (forgetfulness, distractibility, inflexibility and impaired executive functions) involve prefrontal cortex (PFC) dysfunction1, 2, 3, 4. The PFC guides behaviour and thought using working memory5, which are essential functions in the information age. Many PFC neurons hold information in working memory through excitatory networks that can maintain persistent neuronal firing in the absence of external stimulation6. This fragile process is highly dependent on the neurochemical environment7. For example, elevated cyclic-AMP signalling reduces persistent firing by opening HCN and KCNQ potassium channels8, 9. It is not known if molecular changes associated with normal ageing alter the physiological properties of PFC neurons during working memory, as there have been no in vivo recordings, to our knowledge, from PFC neurons of aged monkeys. Here we characterize the first recordings of this kind, revealing a marked loss of PFC persistent firing with advancing age that can be rescued by restoring an optimal neurochemical environment. Recordings showed an age-related decline in the firing rate of DELAY neurons, whereas the firing of CUE neurons remained unchanged with age. The memory-related firing of aged DELAY neurons was partially restored to more youthful levels by inhibiting cAMP signalling, or by blocking HCN or KCNQ channels. These findings reveal the cellular basis of age-related cognitive decline in dorsolateral PFC, and demonstrate that physiological integrity can be rescued by addressing the molecular needs of PFC circuits.
6:08 PM PT: Here is a Yale video on this, however, the narrative talks in such a slow an patronizing way, I can't stand getting through 20 secs of it, without going into a rage, and I'm worried the stress is going to do me harm. If anyone can stomach 4 minutes of this and discovers anything useful please let us know.