Reversal of Age-related Alterations in Synaptic Plasticity by Blockade of L-type Ca2+ Channels

Overview

Journal J Neurosci

Specialty Neurology

Date 1998 May 9

PMID 9547225

Citations 113

Authors

C M Norris

S Halpain

T C Foster

Affiliations

Soon will be listed here.

Abstract

The role of L-type Ca2+ channels in the induction of synaptic plasticity in hippocampal slices of aged (22-24 months) and young adult (4-6 months) male Fischer 344 rats was investigated. Prolonged 1 Hz stimulation (900 pulses) of Schaffer collaterals, which normally depresses CA3/CA1 synaptic strength in aged rat slices, failed to induce long-term depression (LTD) during bath application of the L-channel antagonist nifedipine (10 microM). When 5 Hz stimulation (900 pulses) was used to modify synaptic strength, nifedipine facilitated synaptic enhancement in slices from aged, but not young, adult rats. This enhancement was pathway-specific, reversible, and impaired by the NMDA receptor (NMDAR) antagonist DL-2-amino-5-phosphonopentanoic acid (AP5). Induction of long-term potentiation (LTP) in aged rats, using 100 Hz stimulation, occluded subsequent synaptic enhancement by 5 Hz stimulation, suggesting that nifedipine-facilitated enhancement shares mechanisms in common with conventional LTP. Facilitation of synaptic enhancement by nifedipine likely was attributable to a reduction ( approximately 30%) in the Ca2+-dependent K+-mediated afterhyperpolarization (AHP), because the K+ channel blocker apamin (1 microM) similarly reduced the AHP and promoted synaptic enhancement by 5 Hz stimulation. In contrast, apamin did not block LTD induction using 1 Hz stimulation, suggesting that, in aged rats, the AHP does not influence LTD and LTP induction in a similar way. The results indicate that, during aging, L-channels can (1) facilitate LTD induction during low rates of synaptic activity and (2) impair LTP induction during higher levels of synaptic activation via an increase in the Ca2+-dependent AHP.

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References

ODell T, Kandel E . Low-frequency stimulation erases LTP through an NMDA receptor-mediated activation of protein phosphatases. Learn Mem. 1994; 1(2):129-39. View

Barnes C, Rao G, McNaughton B . Functional integrity of NMDA-dependent LTP induction mechanisms across the lifespan of F-344 rats. Learn Mem. 1996; 3(2-3):124-37. DOI: 10.1101/lm.3.2-3.124. View

Straube K, Deyo R, Moyer Jr J, Disterhoft J . Dietary nimodipine improves associative learning in aging rabbits. Neurobiol Aging. 1990; 11(6):659-61. DOI: 10.1016/0197-4580(90)90033-v. View

deToledo-Morrell L, Geinisman Y, MORRELL F . Age-dependent alterations in hippocampal synaptic plasticity: relation to memory disorders. Neurobiol Aging. 1988; 9(5-6):581-90. DOI: 10.1016/s0197-4580(88)80117-9. View

Sah P, Bekkers J . Apical dendritic location of slow afterhyperpolarization current in hippocampal pyramidal neurons: implications for the integration of long-term potentiation. J Neurosci. 1996; 16(15):4537-42. PMC: 6579026. View

Christie B, Magee J, Johnston D . The role of dendritic action potentials and Ca2+ influx in the induction of homosynaptic long-term depression in hippocampal CA1 pyramidal neurons. Learn Mem. 1996; 3(2-3):160-9. DOI: 10.1101/lm.3.2-3.160. View

Moore C, Browning M, Rose G . Hippocampal plasticity induced by primed burst, but not long-term potentiation, stimulation is impaired in area CA1 of aged Fischer 344 rats. Hippocampus. 1993; 3(1):57-66. DOI: 10.1002/hipo.450030106. View

Lancaster B, Nicoll R . Properties of two calcium-activated hyperpolarizations in rat hippocampal neurones. J Physiol. 1987; 389:187-203. PMC: 1192077. DOI: 10.1113/jphysiol.1987.sp016653. View

Bear M, Abraham W . Long-term depression in hippocampus. Annu Rev Neurosci. 1996; 19:437-62. DOI: 10.1146/annurev.ne.19.030196.002253. View

10.

Coussens C, Kerr D, Abraham W . Glucocorticoid receptor activation lowers the threshold for NMDA-receptor-dependent homosynaptic long-term depression in the hippocampus through activation of voltage-dependent calcium channels. J Neurophysiol. 1997; 78(1):1-9. DOI: 10.1152/jn.1997.78.1.1. View

11.

Landfield P, Pitler T . Prolonged Ca2+-dependent afterhyperpolarizations in hippocampal neurons of aged rats. Science. 1984; 226(4678):1089-92. DOI: 10.1126/science.6494926. View

12.

Bliss T, Collingridge G . A synaptic model of memory: long-term potentiation in the hippocampus. Nature. 1993; 361(6407):31-9. DOI: 10.1038/361031a0. View

13.

Foster T, Norris C . Age-associated changes in Ca(2+)-dependent processes: relation to hippocampal synaptic plasticity. Hippocampus. 1997; 7(6):602-12. DOI: 10.1002/(SICI)1098-1063(1997)7:6<602::AID-HIPO3>3.0.CO;2-G. View

14.

Barnes C, Rao G, Foster T, McNaughton B . Region-specific age effects on AMPA sensitivity: electrophysiological evidence for loss of synaptic contacts in hippocampal field CA1. Hippocampus. 1992; 2(4):457-68. DOI: 10.1002/hipo.450020413. View

15.

Oliet S, Malenka R, Nicoll R . Bidirectional control of quantal size by synaptic activity in the hippocampus. Science. 1996; 271(5253):1294-7. DOI: 10.1126/science.271.5253.1294. View

16.

Bolshakov V, Siegelbaum S . Postsynaptic induction and presynaptic expression of hippocampal long-term depression. Science. 1994; 264(5162):1148-52. DOI: 10.1126/science.7909958. View

17.

Landfield P, Pitler T, Applegate M . The effects of high Mg2+-to-Ca2+ ratios on frequency potentiation in hippocampal slices of young and aged rats. J Neurophysiol. 1986; 56(3):797-811. DOI: 10.1152/jn.1986.56.3.797. View

18.

Wang Y, Salter M . Regulation of NMDA receptors by tyrosine kinases and phosphatases. Nature. 1994; 369(6477):233-5. DOI: 10.1038/369233a0. View

19.

Velisek L, Moshe S, Stanton P . Age dependence of homosynaptic non-NMDA mediated long-term depression in field CA1 of rat hippocampal slices. Brain Res Dev Brain Res. 1993; 75(2):253-60. DOI: 10.1016/0165-3806(93)90029-a. View

20.

Moyer Jr J, Thompson L, Black J, Disterhoft J . Nimodipine increases excitability of rabbit CA1 pyramidal neurons in an age- and concentration-dependent manner. J Neurophysiol. 1992; 68(6):2100-9. DOI: 10.1152/jn.1992.68.6.2100. View