Muscarinic signaling is required for spike‐pairing induction of long‐term potentiation at rat Schaffer collateral‐CA1 synapses

Cholinergic input from the basal forebrain and septum to the hippocampus is well known to be critical in learning and memory. Muscarinic induction of theta‐frequency oscillations may synchronize pre‐ and postsynaptic firing and thereby enhance plasticity in the hippocampus. Previous studies have demonstrated that muscarinic activation facilitates long‐term potentiation (LTP) induced with tetanus in vitro. In the present study, we tested the role of muscarinic receptor activity in the induction of LTP beyond effects on spike timing by using a spike‐pairing (SP) method at Schaffer collateral‐CA1 synapses in rat hippocampal slices. Pairings of pre‐ and postsynaptic action potentials (APs) have been shown to induce LTP when the presynaptic AP precedes the postsynaptic AP by 5–15 ms, but contribution of muscarinic co‐activation has not been ruled out. We demonstrate that the mAChR antagonist atropine abolishes LTP induction by SP. Surprisingly, prolonged exposure to the mAChR agonist carbachol inhibits LTP induction by SP, perhaps because of receptor desensitization. These results demonstrate an essential role of cholinergic signaling in this form of hippocampal plasticity. © 2004 Wiley‐Liss, Inc.

[1]  P. J. Sjöström,et al.  Spike timing, calcium signals and synaptic plasticity , 2002, Current Opinion in Neurobiology.

[2]  W. N. Ross,et al.  Inositol 1,4,5-Trisphosphate (IP3)-Mediated Ca2+ Release Evoked by Metabotropic Agonists and Backpropagating Action Potentials in Hippocampal CA1 Pyramidal Neurons , 2000, The Journal of Neuroscience.

[3]  H. Markram,et al.  Regulation of Synaptic Efficacy by Coincidence of Postsynaptic APs and EPSPs , 1997, Science.

[4]  T. Bliss,et al.  Single Synaptic Events Evoke NMDA Receptor–Mediated Release of Calcium from Internal Stores in Hippocampal Dendritic Spines , 1999, Neuron.

[5]  A. Akaike,et al.  Involvement of M2 receptor in an enhancement of long-term potentiation by carbachol in Schaffer collateral-CA1 synapses of hippocampal slices , 1997, Neuroscience Research.

[6]  John A. Connor,et al.  Cholinergic input uncouples Ca2+ changes from K+ conductance activation and amplifies intradendritic Ca2+ changes in hippocampal neurons , 1991, Neuron.

[7]  W. Buño,et al.  Presynaptic inhibition of Schaffer collateral synapses by stimulation of hippocampal cholinergic afferent fibres , 2003, The European journal of neuroscience.

[8]  C. V. van Koppen,et al.  Regulation of muscarinic acetylcholine receptor signaling. , 2003, Pharmacology & therapeutics.

[9]  W. N. Ross,et al.  Muscarinic modulation of spike backpropagation in the apical dendrites of hippocampal CA1 pyramidal neurons. , 1997, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  U. Heinemann,et al.  Carbachol effects on hippocampal neurons in vitro: dependence on the rate of rise of carbachol tissue concentration , 2004, Experimental Brain Research.

[11]  W. Buño,et al.  Selective muscarinic regulation of functional glutamatergic Schaffer collateral synapses in rat CA1 pyramidal neurons , 2002, The Journal of physiology.

[12]  M. Hasselmo.  Neuromodulation: acetylcholine and memory consolidation , 1999, Trends in Cognitive Sciences.

[13]  D. A. Brown,et al.  Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone , 1980, Nature.

[14]  M. Jung,et al.  Cholinergic modulation of synaptic transmission and plasticity in entorhinal cortex and hippocampus of the rat , 2000, Neuroscience.

[15]  L. Acsády,et al.  Distinct interneuron types express m2 muscarinic receptor immunoreactivity on their dendrites or axon terminals in the hippocampus , 1997, Neuroscience.

[16]  K. Svoboda,et al.  The Life Cycle of Ca2+ Ions in Dendritic Spines , 2002, Neuron.

[17]  P. Saggau,et al.  Presynaptic inhibition of synaptic transmission in the rat hippocampus by activation of muscarinic receptors: involvement of presynaptic calcium influx , 1997, British journal of pharmacology.

[18]  L. Nowak,et al.  Magnesium gates glutamate-activated channels in mouse central neurones , 1984, Nature.

[19]  Michael Frotscher,et al.  Cholinergic innervation of the rat hippocampus as revealed by choline acetyltransferase immunocytochemistry: A combined light and electron microscopic study , 1985, The Journal of comparative neurology.

[20]  Jochen Winterer,et al.  New illumination technique for IR-video guided patch-clamp recording from neurons in slice cultures on biomembrane , 2003, Journal of Neuroscience Methods.

[21]  J. Lisman,et al.  Heightened synaptic plasticity of hippocampal CA1 neurons during a Cholinergically induced rhythmic state , 1993, Nature.

[22]  D. Johnston,et al.  A Synaptically Controlled, Associative Signal for Hebbian Plasticity in Hippocampal Neurons , 1997, Science.

[23]  Robert D. Blitzer,et al.  Cholinergic stimulation enhances long-term potentiation in the CA1 region of rat hippocampus , 1990, Neuroscience Letters.

[24]  B. Gustafsson,et al.  Hippocampal long-lasting potentiation produced by pairing single volleys and brief conditioning tetani evoked in separate afferents , 1986, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  A. Levey,et al.  Localization of M2 muscarinic acetylcholine receptor protein in cholinergic and non-cholinergic terminals in rat hippocampus , 2000, Neuroscience Letters.

[26]  T. Gloveli,et al.  Muscarinic control of dendritic excitability and Ca(2+) signaling in CA1 pyramidal neurons in rat hippocampal slice. , 1999, Journal of neurophysiology.

[27]  B. Sakmann,et al.  Calcium dynamics in single spines during coincident pre- and postsynaptic activity depend on relative timing of back-propagating action potentials and subthreshold excitatory postsynaptic potentials. , 1998, Proceedings of the National Academy of Sciences of the United States of America.