Sci. Aging Knowl. Environ., 30 July 2003
Vol. 2003, Issue 30, p. nw107
[DOI: 10.1126/sageke.2003.30.nw107]


Plugging the Memory Drain

Blocking transport protein improves learning in old mice

R. John Davenport;2003/30/nw107

Key Words: trace conditioning • theta burst stimulation • small-conductance Ca2+-activated K+ channels

Mental acuity dulls with age, making it easy to forget ordinary things, such as how much butter a favorite cookie recipe requires or which cupboard contains the flour. Such lapses might stem from elevated amounts of a brain protein that shuttles potassium, according to a new study. The results suggest that reducing the amount of the protein, which dampens a neuron firing pattern associated with learning, might restore nimble thinking in elderly brains.

Memories begin in a region of the brain called the hippocampus. Repeated stimulation of neurons in that area strengthens the signals they send; many neuroscientists postulate that this phenomenon, called long-term potentiation (LTP), somehow helps the brain hang on to information. Previous studies showed that proteins called SK channels--which let potassium out of neurons and weaken their firing--impair LTP and hinder learning. In the new study, Blank and colleagues tested whether hyperactive SK channels underlie age-related cognitive deficits.

To investigate, the researchers measured the quantity of one type of SK channel, SK3, in hippocampus tissue from young and old mice. The 2-year-old codgers carried nearly 50% more SK protein in their neurons than did the 4- to 6-month-old youngsters. Next, the scientists repeatedly stimulated each sample with an electrode. Old hippocampus neurons displayed less LTP than did adolescent ones. When the team blocked production of SK protein in the old tissue by injecting DNA molecules that abduct SK messenger RNA, LTP rose to a youthful magnitude.

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Down the tubes. Extra SK channels impede memory in old mice. [Source: R. John Davenport; Illustration: Julie White]

By subjecting animals to a standard memory test, the scientists determined whether the extra SK obstructs learning. The researchers trained the mice to associate a noise with pain by sounding a tone, then shocking the rodents' paws. After several rounds, animals typically freeze in fear when the tone is sounded, even without the shock. One day after the training, elderly rodents froze for less time than their younger counterparts did, suggesting that the oldsters hadn't retained the memory as well. Then the researchers infused the brains of old animals with the SK-blocking DNA molecules. The treated oldsters froze as often as did young animals in response to the sound. The results suggest that abundant SK channels impair LTP in old animals and impede their learning.

Previous studies hinted that SK channels might impair memory in aged brains, says neuroscientist Robert Stackman of the Oregon Health & Science University in Portland, but the new work is important because it pinpoints a particular variety, SK3. He'd like to see additional work to establish whether SK3 influences learning in other types of memory tests. Why old animals make bonus SK3 is unclear, he says, but the extra production might be a defense mechanism that guards against overactivity that can kill neurons. Numerous proteins contribute to LTP, so assessing the importance of SK channels will require further work. However, piecing together how LTP and learning deteriorate with age might lead researchers to ways of bolstering fading brains. Now, where's that mixing bowl?

--R. John Davenport

July 30, 2003
  1. T. Blank, I. Nijholt, M.-J. Kye, J. Radulovic, J. Spiess, Small-conductance, Ca2+-activated K+ channel SK3 generates age-related memory and LTP deficits. Nature Neurosci., 27 July 2003 [e-pub ahead of print]. [Abstract/Full Text]
  2. C. M. Norris, S. Halpain, T. C. Foster, Reversal of age-related alterations in synaptic plasticity by blockade of L-type Ca2+ channels. J. Neurosci. 18, 3171-3179 (1998). [Abstract/Free Full Text]
  3. R. W. Stackman et al., Small conductance Ca2+-activated K+ channels modulate synaptic plasticity and memory encoding. J. Neurosci. 22, 10163-10171 (2002). [Abstract/Free Full Text]
Citation: R. J. Davenport, Plugging the Memory Drain. Sci. SAGE KE 2003, nw107 (30 July 2003);2003/30/nw107

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