Regular Research ArticlesInvestigation of Age-Related Cognitive Decline Using Mice as a Model System: Neurophysiological Correlates
Section snippets
Mice
All mice used in these experiments were either raised within our own colony or obtained from the National Institutes on Aging colony at Harlan Sprague Dawley (Indianapolis, IN). Mice raised in our own colony were 8–10 generations backcrossed into the C57Bl/6 background and were used to measure the sAHP. C57BL/6Nia mice obtained from NIA were used in all other experiments. Young animals were 4–6 months of age at the start of the experiments and aged animals were 22–24 months of age.
Slice Preparation
Animals were
Measurements of the Slow Afterhyperpolarization and L-Type Voltage-Dependent Calcium Channel-Dependent Long-Term Potentiation
To determine the extent of the age-related increase in activity-dependent calcium influx, we measured the sAHP in neurons in the CA1 region of the hippocampus in slices from young (seven mice/15 neurons) and aged (four mice/11 neurons) C57BL/6 mice. As illustrated in Figure 1, the sAHP recorded from an aged mouse pyramidal neuron (bottom panel A2) is significantly larger in amplitude at its maximum and persists longer than the sAHP recorded from CA1 pyramidal neurons typically found in the
DISCUSSION
Although there are numerous reports regarding age-related increases in the sAHP in rats (for a recent review, see 46), much less is known about this phenomenon in mice.31 Consistent with the rat literature, we find that there is an age-related increase in the sAHP. These data, together with our observation of an enhanced vdccLTP in aged mice, strongly suggest that there is an increase in activity-dependent cytosolic calcium concentration in neurons within the CA1 region of the hippocampus in
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2019, Neurobiology of Learning and MemoryCitation Excerpt :These recordings revealed an age-related increase in the Ca2+ activated, and K+-mediated, AHP that follows a burst of action potentials (Fig. 1A). An increase in the amplitude of the AHP is now a well-established marker of aging in CA1 pyramidal neurons and has been observed in rabbits, mice, and rats, both male and female (Disterhoft et al., 1996; Kaczorowski & Disterhoft, 2009; Kumar and Foster, 2002, 2004; Landfield & Pitler, 1984; Murphy, Shah, Hell, & Silva, 2006; Power, Wu, Sametsky, Oh, & Disterhoft, 2002; Tombaugh, Rowe, & Rose, 2005). The larger hyperpolarization influences the relative refractory period of the action potential, reducing the number of action potentials evoked during depolarization (spike frequency accommodation) and shifts the discharge activity evoked by distinct patterns of afferent stimulation (Gant & Thibault, 2009).
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This work was supported by NIH grants to AJS (R01 AG17499), JWH (R01 AG17502), and GGM (F32 AG5858). Additional support was provided by the Bank of America Giannini Foundation (GGM) and a faculty scholar award (94-033) from the Alzheimer's Association (JWH).
Dr. Murphy is currently affiliated with the Molecular and Behavioral Neuroscience Institute & Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, Michigan.