Abstract
Long-term depression (LTD) of synaptic efficacy is likely to be as important in memory processing as the more well-known long-term potentiation (LTP). The case for LTD serving as a memory mechanism, however, requires that it be shown to persist across days or weeks at least. Here we examined the persistence of heterosynaptic LTD in the medial and lateral perforant path inputs to the dentate gyrus in awake rats and correlated this persistence with the degree of immediate early gene expression as assessed immunohistochemically. Rats were chronically implanted with separate stimulating electrodes in the medial and lateral perforant paths and an extracellular field potential recording electrode in the dentate hilus. After recovery from surgery, either the medial or the lateral perforant path was tetanized with 400-Hz trains, and homosynaptic LTP and heterosynaptic LTD were followed across time. Heterosynaptic LTD was shown to occur readily in awake animals and to persist across days or weeks, depending on the stimulation protocol. The persistence of LTD and LTP was highly correlated within animals. Additional animals, given the same tetanization protocols, showed that the greatest immediate early gene expression occurred following that protocol which consistently gave the longest-lasting LTP and LTD. These data support the proposed role of LTD in memory processing but question whether immediate early genes are important for the persistence of LTP, LTD, or both.
Full text
PDF




Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Abraham W. C., Dragunow M., Tate W. P. The role of immediate early genes in the stabilization of long-term potentiation. Mol Neurobiol. 1991;5(2-4):297–314. doi: 10.1007/BF02935553. [DOI] [PubMed] [Google Scholar]
- Abraham W. C., Goddard G. V. Asymmetric relationships between homosynaptic long-term potentiation and heterosynaptic long-term depression. Nature. 1983 Oct 20;305(5936):717–719. doi: 10.1038/305717a0. [DOI] [PubMed] [Google Scholar]
- Abraham W. C., Mason S. E., Demmer J., Williams J. M., Richardson C. L., Tate W. P., Lawlor P. A., Dragunow M. Correlations between immediate early gene induction and the persistence of long-term potentiation. Neuroscience. 1993 Oct;56(3):717–727. doi: 10.1016/0306-4522(93)90369-q. [DOI] [PubMed] [Google Scholar]
- Artola A., Singer W. Long-term depression of excitatory synaptic transmission and its relationship to long-term potentiation. Trends Neurosci. 1993 Nov;16(11):480–487. doi: 10.1016/0166-2236(93)90081-v. [DOI] [PubMed] [Google Scholar]
- Bliss T. V., Gardner-Medwin A. R. Long-lasting potentiation of synaptic transmission in the dentate area of the unanaestetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):357–374. doi: 10.1113/jphysiol.1973.sp010274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bliss T. V., Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):331–356. doi: 10.1113/jphysiol.1973.sp010273. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bonhoeffer T., Staiger V., Aertsen A. Synaptic plasticity in rat hippocampal slice cultures: local "Hebbian" conjunction of pre- and postsynaptic stimulation leads to distributed synaptic enhancement. Proc Natl Acad Sci U S A. 1989 Oct;86(20):8113–8117. doi: 10.1073/pnas.86.20.8113. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christie B. R., Abraham W. C. NMDA-dependent heterosynaptic long-term depression in the dentate gyrus of anaesthetized rats. Synapse. 1992 Jan;10(1):1–6. doi: 10.1002/syn.890100102. [DOI] [PubMed] [Google Scholar]
- Christie B. R., Kerr D. S., Abraham W. C. Flip side of synaptic plasticity: long-term depression mechanisms in the hippocampus. Hippocampus. 1994 Apr;4(2):127–135. doi: 10.1002/hipo.450040203. [DOI] [PubMed] [Google Scholar]
- Cole A. J., Saffen D. W., Baraban J. M., Worley P. F. Rapid increase of an immediate early gene messenger RNA in hippocampal neurons by synaptic NMDA receptor activation. Nature. 1989 Aug 10;340(6233):474–476. doi: 10.1038/340474a0. [DOI] [PubMed] [Google Scholar]
- Demmer J., Dragunow M., Lawlor P. A., Mason S. E., Leah J. D., Abraham W. C., Tate W. P. Differential expression of immediate early genes after hippocampal long-term potentiation in awake rats. Brain Res Mol Brain Res. 1993 Mar;17(3-4):279–286. doi: 10.1016/0169-328x(93)90012-e. [DOI] [PubMed] [Google Scholar]
- Dragunow M., Abraham W. C., Goulding M., Mason S. E., Robertson H. A., Faull R. L. Long-term potentiation and the induction of c-fos mRNA and proteins in the dentate gyrus of unanesthetized rats. Neurosci Lett. 1989 Jul 3;101(3):274–280. doi: 10.1016/0304-3940(89)90545-4. [DOI] [PubMed] [Google Scholar]
- Ito M. Long-term depression. Annu Rev Neurosci. 1989;12:85–102. doi: 10.1146/annurev.ne.12.030189.000505. [DOI] [PubMed] [Google Scholar]
- Krug M., Müller-Welde P., Wagner M., Ott T., Matthies H. Functional plasticity in two afferent systems of the granule cells in the rat dentate area: frequency-related changes, long-term potentiation and heterosynaptic depression. Brain Res. 1985 Dec 23;360(1-2):264–272. doi: 10.1016/0006-8993(85)91242-9. [DOI] [PubMed] [Google Scholar]
- Levy W. B., Steward O. Synapses as associative memory elements in the hippocampal formation. Brain Res. 1979 Oct 19;175(2):233–245. doi: 10.1016/0006-8993(79)91003-5. [DOI] [PubMed] [Google Scholar]
- McNaughton B. L., Barnes C. A. Physiological identification and analysis of dentate granule cell responses to stimulation of the medial and lateral perforant pathways in the rat. J Comp Neurol. 1977 Oct 15;175(4):439–454. doi: 10.1002/cne.901750404. [DOI] [PubMed] [Google Scholar]
- Nakazawa K., Karachot L., Nakabeppu Y., Yamamori T. The conjunctive stimuli that cause long-term desensitization also predominantly induce c-Fos and Jun-B in cerebellar Purkinje cells. Neuroreport. 1993 Sep 10;4(11):1275–1278. doi: 10.1097/00001756-199309000-00017. [DOI] [PubMed] [Google Scholar]
- Racine R. J., Milgram N. W., Hafner S. Long-term potentiation phenomena in the rat limbic forebrain. Brain Res. 1983 Feb 7;260(2):217–231. doi: 10.1016/0006-8993(83)90676-5. [DOI] [PubMed] [Google Scholar]
- Richardson C. L., Tate W. P., Mason S. E., Lawlor P. A., Dragunow M., Abraham W. C. Correlation between the induction of an immediate early gene, zif/268, and long-term potentiation in the dentate gyrus. Brain Res. 1992 May 15;580(1-2):147–154. doi: 10.1016/0006-8993(92)90938-6. [DOI] [PubMed] [Google Scholar]
- Schreiber S. S., Maren S., Tocco G., Shors T. J., Thompson R. F. A negative correlation between the induction of long-term potentiation and activation of immediate early genes. Brain Res Mol Brain Res. 1991 Aug;11(1):89–91. doi: 10.1016/0169-328x(91)90025-s. [DOI] [PubMed] [Google Scholar]
- Schuman E. M., Madison D. V. Locally distributed synaptic potentiation in the hippocampus. Science. 1994 Jan 28;263(5146):532–536. doi: 10.1126/science.8290963. [DOI] [PubMed] [Google Scholar]
- Staubli U., Lynch G. Stable hippocampal long-term potentiation elicited by 'theta' pattern stimulation. Brain Res. 1987 Dec 1;435(1-2):227–234. doi: 10.1016/0006-8993(87)91605-2. [DOI] [PubMed] [Google Scholar]
- White G., Levy W. B., Steward O. Spatial overlap between populations of synapses determines the extent of their associative interaction during the induction of long-term potentiation and depression. J Neurophysiol. 1990 Oct;64(4):1186–1198. doi: 10.1152/jn.1990.64.4.1186. [DOI] [PubMed] [Google Scholar]
- Wisden W., Errington M. L., Williams S., Dunnett S. B., Waters C., Hitchcock D., Evan G., Bliss T. V., Hunt S. P. Differential expression of immediate early genes in the hippocampus and spinal cord. Neuron. 1990 Apr;4(4):603–614. doi: 10.1016/0896-6273(90)90118-y. [DOI] [PubMed] [Google Scholar]