Aging Impairs Intermediate-term Behavioral Memory by Disrupting the Dorsal Paired Medial Neuron Memory Trace

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2012 Apr 5

PMID 22474396

Citations 25

Authors

Ayako Tonoki

Ronald L Davis

Affiliations

Soon will be listed here.

Abstract

How the functional activity of the brain is altered during aging to cause age-related memory impairments is unknown. We used functional cellular imaging to monitor two different calcium-based memory traces that underlie olfactory classical conditioning in young and aged Drosophila. Functional imaging of neural activity in the processes of the dorsal paired medial (DPM) and mushroom body neurons revealed that the capacity to form an intermediate-term memory (ITM) trace in the DPM neurons after learning is lost with age, whereas the capacity to form a short-term memory trace in the α'/β' mushroom body neurons remains unaffected by age. Stimulation of the DPM neurons by activation of a temperature-sensitive cation channel between acquisition and retrieval enhanced ITM in aged but not young flies. These data indicate that the functional state of the DPM neurons is selectively altered with age to cause an age-related impairment of ITM, and demonstrate that altering the excitability of DPM neurons can restore age-related memory impairments.

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References

Keene A, Stratmann M, Keller A, Perrat P, Vosshall L, Waddell S . Diverse odor-conditioned memories require uniquely timed dorsal paired medial neuron output. Neuron. 2004; 44(3):521-33. DOI: 10.1016/j.neuron.2004.10.006. View

Peier A, Moqrich A, Hergarden A, Reeve A, Andersson D, Story G . A TRP channel that senses cold stimuli and menthol. Cell. 2002; 108(5):705-15. DOI: 10.1016/s0092-8674(02)00652-9. View

Davis R . Traces of Drosophila memory. Neuron. 2011; 70(1):8-19. PMC: 3374581. DOI: 10.1016/j.neuron.2011.03.012. View

Cabeza R, Anderson N, Locantore J, McIntosh A . Aging gracefully: compensatory brain activity in high-performing older adults. Neuroimage. 2002; 17(3):1394-402. DOI: 10.1006/nimg.2002.1280. View

Quinn W, Sziber P, Booker R . The Drosophila memory mutant amnesiac. Nature. 1979; 277(5693):212-4. DOI: 10.1038/277212a0. View

Wang Y, Mamiya A, Chiang A, Zhong Y . Imaging of an early memory trace in the Drosophila mushroom body. J Neurosci. 2008; 28(17):4368-76. PMC: 3413309. DOI: 10.1523/JNEUROSCI.2958-07.2008. View

Issa A, Rowe W, Gauthier S, Meaney M . Hypothalamic-pituitary-adrenal activity in aged, cognitively impaired and cognitively unimpaired rats. J Neurosci. 1990; 10(10):3247-54. PMC: 6570181. View

Akalal D, Yu D, Davis R . A late-phase, long-term memory trace forms in the γ neurons of Drosophila mushroom bodies after olfactory classical conditioning. J Neurosci. 2010; 30(49):16699-708. PMC: 3380342. DOI: 10.1523/JNEUROSCI.1882-10.2010. View

Yu D, Akalal D, Davis R . Drosophila alpha/beta mushroom body neurons form a branch-specific, long-term cellular memory trace after spaced olfactory conditioning. Neuron. 2006; 52(5):845-55. PMC: 1779901. DOI: 10.1016/j.neuron.2006.10.030. View

10.

Wang M, Gamo N, Yang Y, Jin L, Wang X, Laubach M . Neuronal basis of age-related working memory decline. Nature. 2011; 476(7359):210-3. PMC: 3193794. DOI: 10.1038/nature10243. View

11.

Cabeza R . Hemispheric asymmetry reduction in older adults: the HAROLD model. Psychol Aging. 2002; 17(1):85-100. DOI: 10.1037//0882-7974.17.1.85. View

12.

Wang Y, Guo H, Pologruto T, Hannan F, Hakker I, Svoboda K . Stereotyped odor-evoked activity in the mushroom body of Drosophila revealed by green fluorescent protein-based Ca2+ imaging. J Neurosci. 2004; 24(29):6507-14. PMC: 6729867. DOI: 10.1523/JNEUROSCI.3727-03.2004. View

13.

Waddell S, Armstrong J, Kitamoto T, Kaiser K, Quinn W . The amnesiac gene product is expressed in two neurons in the Drosophila brain that are critical for memory. Cell. 2000; 103(5):805-13. DOI: 10.1016/s0092-8674(00)00183-5. View

14.

Andrews-Hanna J, Snyder A, Vincent J, Lustig C, Head D, Raichle M . Disruption of large-scale brain systems in advanced aging. Neuron. 2007; 56(5):924-35. PMC: 2709284. DOI: 10.1016/j.neuron.2007.10.038. View

15.

Peabody N, Pohl J, Diao F, Vreede A, Sandstrom D, Wang H . Characterization of the decision network for wing expansion in Drosophila using targeted expression of the TRPM8 channel. J Neurosci. 2009; 29(11):3343-53. PMC: 2717795. DOI: 10.1523/JNEUROSCI.4241-08.2009. View

16.

Cheng Y, Endo K, Wu K, Rodan A, Heberlein U, Davis R . Drosophila fasciclinII is required for the formation of odor memories and for normal sensitivity to alcohol. Cell. 2001; 105(6):757-68. DOI: 10.1016/s0092-8674(01)00386-5. View

17.

Liu X, Davis R . The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning. Nat Neurosci. 2008; 12(1):53-9. PMC: 2680707. DOI: 10.1038/nn.2235. View

18.

Bach M, Barad M, Son H, Zhuo M, Lu Y, Shih R . Age-related defects in spatial memory are correlated with defects in the late phase of hippocampal long-term potentiation in vitro and are attenuated by drugs that enhance the cAMP signaling pathway. Proc Natl Acad Sci U S A. 1999; 96(9):5280-5. PMC: 21855. DOI: 10.1073/pnas.96.9.5280. View

19.

Wang J, Wong A, Flores J, Vosshall L, Axel R . Two-photon calcium imaging reveals an odor-evoked map of activity in the fly brain. Cell. 2003; 112(2):271-82. DOI: 10.1016/s0092-8674(03)00004-7. View

20.

Krashes M, Keene A, Leung B, Armstrong J, Waddell S . Sequential use of mushroom body neuron subsets during drosophila odor memory processing. Neuron. 2007; 53(1):103-15. PMC: 1828290. DOI: 10.1016/j.neuron.2006.11.021. View