Muscarinic acetylcholine receptors and voltage-gated calcium channels contribute to bidirectional synaptic plasticity at CA1-subiculum synapses

Hippocampal output is mediated via the subiculum, which is the principal target of CA1 pyramidal cells, and which sends projections to a variety of cortical and subcortical regions. Pyramidal cells in the subiculum display two different firing modes and are classified as being burst-spiking or regular-spiking. In a previous study, we found that low-frequency stimulation induces an NMDA receptor-dependent long-term depression (LTD) in burst-spiking cells and a metabotropic glutamate receptor-dependent long-term potentiation (LTP) in regular-spiking cells [P. Fidzinski, O. Shor, J. Behr, Target-cell-specific bidirectional synaptic plasticity at hippocampal output synapses, Eur. J. Neurosci., 27 (2008) 1111-1118]. Here, we present evidence that this bidirectional plasticity relies upon the co-activation of muscarinic acetylcholine receptors, as scopolamine blocks synaptic plasticity in both cell types. In addition, we demonstrate that the L-type calcium channel inhibitor nifedipine converts LTD to LTP in burst-spiking cells and LTP to LTD in regular-spiking cells, indicating that the polarity of synaptic plasticity is modulated by voltage-gated calcium channels. Bidirectional synaptic plasticity in subicular cells therefore appears to be governed by a complex signaling system, involving cell-specific recruitment of ligand and voltage-gated ion channels as well as metabotropic receptors. This complex regulation might be necessary for fine-tuning of synaptic efficacy at hippocampal output synapses.

[1]  B. Sabatini,et al.  Regulation of synaptic signalling by postsynaptic, non‐glutamate receptor ion channels , 2008, The Journal of physiology.

[2]  M. Kokaia.  Long‐term potentiation of single subicular neurons in mice , 2000, Hippocampus.

[3]  Christian Wozny,et al.  Cellular and network properties of the subiculum in the pilocarpine model of temporal lobe epilepsy , 2005, The Journal of comparative neurology.

[4]  F. H. Lopes da Silva,et al.  Anatomic organization and physiology of the limbic cortex. , 1990, Physiological reviews.

[5]  L Menendez de la Prida,et al.  Electrophysiological and morphological diversity of neurons from the rat subicular complex in vitro , 2003, Hippocampus.

[6]  J. Wess,et al.  M1 Muscarinic Acetylcholine Receptors Activate Extracellular Signal-Regulated Kinase in CA1 Pyramidal Neurons in Mouse Hippocampal Slices , 2001, Molecular and Cellular Neuroscience.

[7]  B. Sakmann,et al.  Spine Ca2+ Signaling in Spike-Timing-Dependent Plasticity , 2006, The Journal of Neuroscience.

[8]  M. S. Berry,et al.  Criteria for distinguishing between monosynaptic and polysynaptic transmission , 1976, Brain Research.

[9]  Oded Shor,et al.  Target‐cell‐specific bidirectional synaptic plasticity at hippocampal output synapses , 2008, The European journal of neuroscience.

[10]  R K Wong,et al.  Intrinsic properties and evoked responses of guinea pig subicular neurons in vitro. , 1993, Journal of neurophysiology.

[11]  S. J. Martin,et al.  Synaptic plasticity and memory: an evaluation of the hypothesis. , 2000, Annual review of neuroscience.

[12]  S M O'Mara,et al.  The projection from hippocampal area CA1 to the subiculum sustains long‐term potentiation , 1998, Neuroreport.

[13]  M. Caulfield.  Muscarinic receptors--characterization, coupling and function. , 1993, Pharmacology & therapeutics.

[14]  M. Berridge.  Neuronal Calcium Signaling , 1998, Neuron.

[15]  D. Amaral,et al.  The Hippocampal Formation , 2009 .

[16]  S. O’Mara,et al.  The subiculum: a review of form, physiology and function , 2001, Progress in Neurobiology.

[17]  U. Gerber,et al.  Muscarinic receptor stimulation reduces NMDA responses in CA3 hippocampal pyramidal cells via Ca2+-dependent activation of tyrosine phosphatase , 2005, Neuropharmacology.

[18]  Stephen J Redman,et al.  Spatial segregation of neuronal calcium signals encodes different forms of LTP in rat hippocampus , 2006, The Journal of physiology.

[19]  D. Purves,et al.  Monosynaptic chemical and electrical connexions between sensory and motor cells in the central nervous system of the leech , 1970, The Journal of physiology.

[20]  Franz Hofmann,et al.  Role of Hippocampal Cav1.2 Ca2+ Channels in NMDA Receptor-Independent Synaptic Plasticity and Spatial Memory , 2005, The Journal of Neuroscience.

[21]  M. Mesulam,et al.  Central cholinergic pathways in the rat: An overview based on an alternative nomenclature (Ch1–Ch6) , 1983, Neuroscience.

[22]  Eric R Kandel,et al.  Theta frequency stimulation up-regulates the synaptic strength of the pathway from CA1 to subiculum region of hippocampus. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[23]  Lin Xu,et al.  Long-term depression in rat CA1-subicular synapses depends on the G-protein coupled mACh receptors , 2005, Neuroscience Research.

[24]  B. Billups,et al.  Synaptic Activity Augments Muscarinic Acetylcholine Receptor-stimulated Inositol 1,4,5-Trisphosphate Production to Facilitate Ca2+ Release in Hippocampal Neurons* , 2004, Journal of Biological Chemistry.

[25]  T J Teyler,et al.  VDCCs and NMDARs underlie two forms of LTP in CA1 hippocampus in vivo. , 1999, Journal of neurophysiology.

[26]  D. Johnston,et al.  Contribution of voltage-gated Ca2+ channels to homosynaptic long-term depression in the CA1 region in vitro. , 1997, Journal of neurophysiology.

[27]  M. Poo,et al.  Calcium stores regulate the polarity and input specificity of synaptic modification , 2000, Nature.

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

[29]  M. Bear,et al.  LTP and LTD An Embarrassment of Riches , 2004, Neuron.

[30]  Kamal Sen,et al.  Increasing Ca2+ transients by broadening postsynaptic action potentials enhances timing-dependent synaptic depression. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Hasselmo.  The role of acetylcholine in learning and memory , 2006, Current Opinion in Neurobiology.

[32]  R K Wong,et al.  Inhibitory control of local excitatory circuits in the guinea‐pig hippocampus. , 1987, The Journal of physiology.

[33]  N Spruston,et al.  Resting and active properties of pyramidal neurons in subiculum and CA1 of rat hippocampus. , 2000, Journal of neurophysiology.

[34]  Robert E Hampson,et al.  Differential but Complementary Mnemonic Functions of the Hippocampus and Subiculum , 2004, Neuron.

[35]  J. Taube.  Electrophysiological properties of neurons in the rat subiculum in vitro , 2004, Experimental Brain Research.

[36]  A. Mason,et al.  Neuronal diversity in the subiculum: correlations with the effects of somatostatin on intrinsic properties and on GABA-mediated IPSPs in vitro. , 1996, Journal of Neurophysiology.

[37]  N. Spruston,et al.  Distribution of bursting neurons in the CA1 region and the subiculum of the rat hippocampus , 2008, The Journal of comparative neurology.

[38]  G. Paxinos.  The Rat nervous system , 1985 .

[39]  W. Regehr,et al.  Short-term synaptic plasticity. , 2002, Annual review of physiology.

[40]  W. Guido,et al.  Ablation of Ca2+ Channel β3 Subunit Leads to Enhanced N-Methyl-d-aspartate Receptor-dependent Long Term Potentiation and Improved Long Term Memory* , 2008, Journal of Biological Chemistry.

[41]  G H Glover,et al.  Separate neural bases of two fundamental memory processes in the human medial temporal lobe. , 1997, Science.

[42]  N. Spruston,et al.  Action Potential Bursting in Subicular Pyramidal Neurons Is Driven by a Calcium Tail Current , 2001, The Journal of Neuroscience.

[43]  M. Stewart,et al.  Intrinsic connectivity of the rat subiculum: II. Properties of synchronous spontaneous activity and a demonstration of multiple generator regions , 2001, The Journal of comparative neurology.

[44]  A. Levey,et al.  Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. , 2004, Progress in brain research.

[45]  N. Kato,et al.  Blocking L-type calcium channels enhances long-term depression induced by low-frequency stimulation at hippocampal CA1 synapses , 2006, Brain Research.

[46]  D. Prince,et al.  Ionic mechanisms of cholinergic excitation in mammalian hippocampal pyramidal cells , 1982, Brain Research.

[47]  Z. Bashir.  On long-term depression induced by activation of G-protein coupled receptors , 2003, Neuroscience Research.