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A novel cholinergic induction of long-term potentiation in rat hippocampus
Abstract
1. We studied long-term cholinergic effects on synaptic transmission in submerged hippocampal slices using intra- and extracellular recording techniques. 2. Bath application of submicromolar concentrations of carbachol (CCh) produced a gradually developing, long-lasting increase in the CA1 excitatory postsynaptic potential and population spike. This potentiation was blocked by atropine and, hence, named muscarinic long-term potentiation (LTPm). Application of DL-2-amino-5-phosphonovaleric acid had no effect on LTPm, indicating that this phenomenon is N-methyl-D-aspartate receptor independent. 3. These effects of CCh were not likely to be due to the blockade of one of several K+ conductances by the drug; the time and concentration dependence of LTPm were different from those associated with cholinergic blockade of K+ conductances. 4. Removal of extracellular calcium (Cao2+) from the bath blocked synaptic transmission. CCh added in calcium-free medium induced LTPm, which was revealed upon removal of the drug by washing with normal calcium-containing medium. Neither cutting CA1-CA3 connections nor cessation of synaptic stimulation interfered with LTPm induction. 5. Application of thapsigargin or H-7 together with CCh blocked LTPm, suggesting the involvement of intracellular calcium (Cai2+) stores and protein kinases, respectively, in the LTPm mechanism. 6. Subthreshold cholinergic stimulation coupled with subthreshold tetanic stimulation caused LTP. CCh had no effect when administered after the LTP mechanism had been saturated by repeated suprathreshold tetani. Tetanic stimulation failed to cause LTP when applied after LTPm had been induced by CCh. These experiments indicate that tetanus-induced potentiation and LTPm share a common mechanism and provide a direct link between ACh and mechanisms of synaptic plasticity.
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“The enhancement of long-term encoding could be at least partially mediated by the cholinergic enhancement of long-term potentiation in the hippocampus (Blitzer et al., 1990; Burgard and Sarvey, 1990; Auerbach and Segal, 1994; Isaac et al., 2009).”
From Modes and models of forebrain cholinergic neuromodulation of cognition (2011) · cites this paper as Auerbach and Segal, 1994
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Items 101–166 of 166
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“We have shown previously that cholinergic modulation of synaptic transmission and plasticity in the superficial (II/III) layers of the rat entorhinal cortex (EC) is similar, but not identical, to that in the hippocampal CA1 area (Auerbach and Segal, 1994, 1996; Yun et al., 2000a).”
ResultThe effects of galanin on long-term synaptic plasticity in the CA1 area of rodent hippocampus
Coumis, U., & Davies, C. H. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00007-6 · Cited by 30
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“The carbamate AChE blocker, physostigmine (1 lm; Oh et al., 1999), served to block AChE catalytic activity, whereas the non-degradable ACh analogue, carbachol (CCh, 0.5 lm; Auerbach & Segal, 1994) was used to activate ACh receptors.”
MethodInfluentialHabib, D., & Dringenberg, H. C. (2008) · Hippocampus · doi:10.1002/hipo.20507 · Cited by 25
“…LTP) induction at hippocampal synapses in vitro and in vivo (Krnjević and Ropert, 1982; Markram and Segal, 1990; Huerta and Lisman, 1993; Auerbach and Segal, 1994; Leung et al., 2003; Ovsepian et al., 2004; Dringenberg et al., 2008), effects that can be mediated by both muscarinic…”
BackgroundEnhancement of Cortical Plasticity by Behavioral Training in Acetylcholine-Depleted Adult Rats
Sachdev, R. N. S., Egli, M., Stonecypher, M., Wiley, R. G., & Ebner, F. F. (2000) · Journal of Neurophysiology · doi:10.1152/jn.2000.84.4.1971 · Cited by 25
“In addition to direct postsynaptic effects of ACh, it can modulate glutamatergic transmission in the cortex (Aoki and Kabak 1992; Auerbach and Segal 1994; Krnjevic et al. 1971; Metherate et al. 1987, 1988a,b; Mrzljak et al. 1993).”
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EPO induces changes in synaptic transmission and plasticity in the dentate gyrus of rats
Almaguer‐Melian, W., Mercerón‐Martínez, D., Delgado‐Ocaña, S., Fuentes, N. P., Ledón, N., & Bergado, J. A. (2016) · Synapse · doi:10.1002/syn.21895 · Cited by 23
“Earlier reports show that other chemical substances like the muscarinic cholinergic agonist carbachol (Auerbach and Segal, 1994) or the neurotrophin BDNF induce a pharmacological LTP (Ying et al., 2002) with a similar time-course to that seen after EPO.”
BackgroundResultMans, R. A., Warmus, B. A., Smith, C. C., et al. (2014) · Journal of Neurophysiology · doi:10.1152/jn.00048.2014 · Cited by 24
“vitro (Auerbach and Segal 1994).”
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“…processing has become of considerable interest because of ACh's involvement in behavioural processes related to selective attention, arousal, motivation and reward (reviewed in Semba, 1991), as well as in cellular plasticity (Hars et al., 1993; Auerbach and Segal, 1994; Ahissar et al., in press).”
BackgroundKanju, P. M., Parameshwaran, K., Sims‐Robinson, C., Uthayathas, S., Josephson, E. M., Rajakumar, N., Dhanasekaran, M., & Suppiramaniam, V. D. (2012) · PLoS ONE · doi:10.1371/journal.pone.0031073 · Cited by 28
“In addition, cholinergic receptors in the MS and hippocampus have been shown to modulate LTP [17,18,19,20,21,22].”
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Hebbian synapses in cortical and hippocampal pathways
Skrebitsky, V. G., & Chepkova, A. N. (1998) · Reviews in the Neurosciences · doi:10.1515/revneuro.1998.9.4.243 · Cited by 19
Priming of GABAergic Long-term Potentiation by Muscarinic Receptors
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“…effects of cholinergic drugs on LTP in the hippocampal CA1 in vitro (Segal and Auerbach, 1997; Shimoshige et al., 1997; Yun et al., 2000; Ye et al., 2001; but see Auerbach and Segal, 1994, 1996), and the experimental and analytical design used here may not have been sensitive to such small changes.”
BackgroundCholinergic modulation of neocortical long-term potentiation in the awake, freely moving rat
Boyd, T. E., Trepel, C., & Racine, R. J. (2000) · Brain Research · doi:10.1016/s0006-8993(00)02720-7 · Cited by 19
“Baseline measures and induction of LTP shown to occlude subsequent LTP induction by electrical stimulation [3], suggesting that these two forms of LTP Electrical stimuli were produced by a Grass S88 share a common substrate.”
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“Furthermore, mAChR activation facilitates long-term potentiation (LTP) and produces lasting potentiation of synaptic transmission (Auerbach and Segal 1996, 1994; Blitzer et al. 1990; Brocher et al. 1992; Huerta and Lisman 1993; Ito et al. 1988; Kojima and Onodera 1998; Li et al. 2007; Patil et al.…”
BackgroundStress-induced altered cholinergic–glutamatergic interactions in the mouse hippocampus
Pavlovsky, L., Bitan, Y., Shalev, H., Serlin, Y., & Friedman, A. (2012) · Brain Research · doi:10.1016/j.brainres.2012.05.057 · Cited by 19
“These modulatory cholinergic functions were shown to be involved in synaptic plasticity and, under specific experimental protocols, to be associated with long-term potentiation of glutamatergicmediated synaptic potentials (Auerbach and Segal, 1994).”
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“One notable difference is that, in contrast to the hippocampal CAI area (Auerbach and Segal 1994, 1996), no long-lasting increase of responses evoked in horizontal pathways was induced by low (0.5 yM) concentration of carbachol.”
BackgroundInfluentialDringenberg, H. C., de Oliveira, D. P., & Habib, D. (2008) · Learning & Memory · doi:10.1101/lm.778108 · Cited by 16
“Muscarinic receptor activation is known to enhance hippocampal LTP in vitro and in vivo (Huerta and Lisman 1993; Auerbach and Segal 1994; Leung et al. 2003; Ovsepian et al. 2004).”
BackgroundSubunit-dependent modulation of kainate receptors by muscarinic acetylcholine receptors
Benveniste, M., Wilhelm, J. C., Dingledine, R. J., & Mott, D. D. (2010) · Brain Research · doi:10.1016/j.brainres.2010.07.029 · Cited by 15
“…– see front matter © 2010 Elsevi doi:10.1016/j.brainres.2010.07.029 A B S T R A C T Article history: Accepted 13 July 2010 Available online 23 July 2010 Interactions between cholinergic and glutamatergic neurotransmitter systems influence synaptic transmission and plasticity.”
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Prenatal cocaine exposure leads to enhanced long-term potentiation in region CA1 of hippocampus
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“75 mM, of CCh alone may induce LTP through muscarinic receptors but not NMDA receptors.(34) In this study, 50 nM CCh alone may not be able to induce LTP, suggesting subthreshold cholinergic stimulation.”
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Self-citationAge-dependent local modulation of hippocampal-evoked responses to perforant path stimulation
Levkovitz, Y., & Segal, M. (1998) · Neurobiology of Aging · doi:10.1016/s0197-4580(98)00068-2 · Cited by 11
Self-citationAmnesia of inhibitory avoidance by scopolamine is overcome by previous open-field exposurePreprint
Colettis, N. C., Snitcofsky, M., Kornisiuk, E. E., Gonzalez, E. N., Quillfeldt, J. A., & Jerusalinsky, D. A. (2014) · Learning & Memory · doi:10.1101/lm.036210.114 · Cited by 11
“Either the release of endogenous ACh in vivo (Leung et al. 2003; Ovsepian et al. 2004) or the exogenous application of MAChR agonists in vitro, led to LTP facilitation (Boddeke et al. 1992; Shimoshige et al. 1997; Shinoe et al. 2005).”
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“Importantly, in addition to an action on LTP induced by tetanic stimulation [30, 31], cholinergic-muscarinic receptor activation in vitro can induce LTP of the fEPSP in CA1 without high-frequency stimulation of glutamatergic fibers [ 32 , 33].”
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“Later, in 1994, Auerbach and Segal showed a direct link between ACh and cholinergic effects on synaptic transmission and synaptic plasticity in rat hippocampal slices (Auerbach and Segal 1994).”
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“The study showed that EPO is able to induce a slowly-developing potentiation at the perforant pathway-granule cells synapses, similar to that caused by the administration of BDNF or muscarinic agonists (Auerbach and Segal, 1994; Ying et al., 2002) and facilitates the induction of LTP or LTD, while prevents depotentiat…”
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“The calcium elevation of postsynaptic neurons can subsequently facilitate AMPA receptor traf fi cking and postsynaptic plasticity (Lynch et al., 1983; Malenka et al., 1988; Auerbach and Segal, 1994; Wang et al., 1996; Berridge, 1998; Yang et al., 1999; Zucker, 1999; Bredt and Nicoll, 2003).”
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“There is broad evidence showing the 9 regulatory action of the cholinergic system on hippocampal-dependent memory 10 (Auerbach & Segal, 1994; Blitzer, Gil, & Landau, 1990; Shinoe, Matsui, Taketo, & 11 Manabe, 2005), an effect possibly modulated by M1 subtype mAChRs (Boddeke, Enz, 12 & Shapiro,…”
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Metadata
- Authors
- Auerbach, J. M., & Segal, M.
- Affiliations
- Weizmann Institute of Science (IL)
- ORCID
- Segal, M.
- Venue
- Journal of Neurophysiology
- Publisher
- American Physiological Society
- Published
- 1994-10-01
- Volume
- 72
- Issue
- 4
- Pages
- 2034-2040
- ISSN
- 0022-3077 (ISSN-L)
- 1522-1598
- OpenAlex
- W1959981723
- Cited by
- 166
- References
- 0
- Citations by year
- 2025: 2 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 9 · 2013: 6 · 2012: 10
- FWCI
- 2.57
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurophysiology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Keywords
- carbachol, muscarinic receptors, hippocampal CA1, excitatory postsynaptic potentials, population spike, intracellular calcium stores, protein kinases, tetanic stimulation, synaptic transmission
- MeSH terms
- Acetylcholine, Animals, Cholinergic Fibers, Hippocampus, Male, Synaptic Transmission, Neuronal Plasticity, Receptors, Cholinergic, Synapses, Rats, Wistar, Long-Term Potentiation, Culture Techniques, Rats
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