Endocannabinoid-Dependent Long-Term Potentiation of Synaptic Transmission at Rat Barrel Cortex

Brain-derived neurotrophic factor (BDNF) plays a critical role in modulating plasticity in sensory cortices. Indeed, a BDNF-dependent long-term potentiation (LTP) at distal basal excitatory synapses of Layer 5 pyramidal neurons (L5PNs) has been demonstrated in disinhibited rat barrel cortex slices. Although it is well established that this LTP requires the pairing of excitatory postsynaptic potentials (PSPs) with Ca2+ spikes, its induction when synaptic inhibition is working remains unexplored. Here we show that low-frequency stimulation at basal dendrites of L5PNs is able to trigger a PSP followed by an action potential (AP) and a slow depolarization (termed PSP-Ca2+ response) in thalamocortical slices without blocking synaptic inhibition. We demonstrate that AP barrage-mediated release of endocannabinoids (eCBs) from the recorded L5PNs induces PSP-Ca2+ response facilitation and BDNF-dependent LTP. Indeed, this LTP requires the type 1 cannabinoid receptors activation, is prevented by postsynaptic intracellular 1,2-bis(2-aminophenoxy) ethane-N,N,N,N'-tetraacetic acid (BAPTA) or the anandamide membrane transporter inhibitor AM404, and only occurs in L5PNs neurons showing depolarization-induced suppression of inhibition. Additionally, electrical stimulation at the posteromedial thalamic nucleus induced similar response and LTP. These results reveal a novel form of eCB-dependent LTP at L5PNs that could be relevant in the processing of sensory information in the barrel cortex.

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

[2]  Johannes J. Letzkus,et al.  Requirement of dendritic calcium spikes for induction of spike‐timing‐dependent synaptic plasticity , 2006, The Journal of physiology.

[3]  E. Schuman.  Neurotrophin regulation of synaptic transmission , 1999, Current Opinion in Neurobiology.

[4]  Y. Dan,et al.  Spike-timing-dependent synaptic plasticity depends on dendritic location , 2005, Nature.

[5]  W. Gan,et al.  Branch-specific dendritic Ca2+ spikes cause persistent synaptic plasticity , 2015, Nature.

[6]  Masahiko Watanabe,et al.  Endocannabinoid-mediated control of synaptic transmission. , 2009, Physiological reviews.

[7]  A. Nuñez,et al.  Cholinergic-mediated response enhancement in barrel cortex layer V pyramidal neurons. , 2012, Journal of neurophysiology.

[8]  E. Levine,et al.  Endocannabinoids Mediate Rapid Retrograde Signaling At Interneuron → Pyramidal Neuron Synapses of the Neocortex , 2003 .

[9]  L. Petrocellis,et al.  Endocannabinoids: endogenous cannabinoid receptor ligands with neuromodulatory action , 1998, Trends in Neurosciences.

[10]  B. Sakmann,et al.  Calcium electrogenesis in distal apical dendrites of layer 5 pyramidal cells at a critical frequency of back-propagating action potentials. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  E. Capaldi,et al.  The organization of behavior. , 1992, Journal of applied behavior analysis.

[12]  M. London,et al.  Dendritic computation. , 2005, Annual review of neuroscience.

[13]  Gareth Williams,et al.  BDNF regulates neuronal sensitivity to endocannabinoids , 2009, Neuroscience Letters.

[14]  Bartlett W. Mel,et al.  Encoding and Decoding Bursts by NMDA Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons , 2009, The Journal of Neuroscience.

[15]  D. Lovinger,et al.  Disruption of Endocannabinoid Release and Striatal Long-Term Depression by Postsynaptic Blockade of Endocannabinoid Membrane Transport , 2004, The Journal of Neuroscience.

[16]  M. Elphick,et al.  Comparative analysis of fatty acid amide hydrolase and cb1 cannabinoid receptor expression in the mouse brain: evidence of a widespread role for fatty acid amide hydrolase in regulation of endocannabinoid signaling , 2003, Neuroscience.

[17]  Arthur Konnerth,et al.  Postsynaptic Induction of BDNF-Mediated Long-Term Potentiation , 2002, Science.

[18]  Ken Mackie,et al.  Endocannabinoid Signaling in Rat Somatosensory Cortex: Laminar Differences and Involvement of Specific Interneuron Types , 2005, The Journal of Neuroscience.

[19]  N. Spruston,et al.  Dendritic spikes induce single-burst long-term potentiation , 2007, Proceedings of the National Academy of Sciences.

[20]  A. Holtmaat,et al.  Sensory-evoked LTP driven by dendritic plateau potentials in vivo , 2014, Nature.

[21]  B. Kampa,et al.  Calcium Spikes in Basal Dendrites of Layer 5 Pyramidal Neurons during Action Potential Bursts , 2006, The Journal of Neuroscience.

[22]  E. Levine,et al.  Endocannabinoids mediate rapid retrograde signaling at interneuron right-arrow pyramidal neuron synapses of the neocortex. , 2003, Journal of neurophysiology.

[23]  B. Connors,et al.  Thalamocortical responses of mouse somatosensory (barrel) cortexin vitro , 1991, Neuroscience.

[24]  E. G. Jones,et al.  Organized growth of thalamocortical axons from the deep tier of terminations into layer IV of developing mouse barrel cortex , 1993, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[25]  G. Collingridge,et al.  A comparison of paired-pulse facilitation of AMPA and NMDA receptor-mediated excitatory postsynaptic currents in the hippocampus , 1994, Experimental Brain Research.

[26]  E. Levine,et al.  BDNF-endocannabinoid interactions at neocortical inhibitory synapses require phospholipase C signaling. , 2014, Journal of neurophysiology.

[27]  P. J. Sjöström,et al.  Neocortical LTD via Coincident Activation of Presynaptic NMDA and Cannabinoid Receptors , 2003, Neuron.

[28]  Thomas J Younts,et al.  Endogenous cannabinoid signaling at inhibitory interneurons , 2014, Current Opinion in Neurobiology.

[29]  Yue Wang,et al.  Endocannabinoids facilitate the induction of LTP in the hippocampus , 2002, Nature Neuroscience.

[30]  K. Svoboda,et al.  The subcellular organization of neocortical excitatory connections , 2009, Nature.

[31]  A. Araque,et al.  Endocannabinoids Potentiate Synaptic Transmission through Stimulation of Astrocytes , 2010, Neuron.

[32]  G. Lynch,et al.  Paired‐pulse and frequency facilitation in the CA1 region of the in vitro rat hippocampus , 1980, The Journal of physiology.

[33]  Y. Dan,et al.  Spike timing-dependent plasticity: from synapse to perception. , 2006, Physiological reviews.

[34]  D. O. Hebb,et al.  The organization of behavior , 1988 .

[35]  M. Kano,et al.  Presynaptic Cannabinoid Sensitivity Is a Major Determinant of Depolarization-Induced Retrograde Suppression at Hippocampal Synapses , 2002, The Journal of Neuroscience.

[36]  P. Jonas,et al.  Kinetics of Mg2+ unblock of NMDA receptors: implications for spike‐timing dependent synaptic plasticity , 2004, The Journal of physiology.

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

[38]  R. Nicoll,et al.  Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses , 2001, Nature.

[39]  M. Larkum.  A cellular mechanism for cortical associations: an organizing principle for the cerebral cortex , 2013, Trends in Neurosciences.

[40]  D. Fortin,et al.  Differential effects of endocannabinoids on glutamatergic and GABAergic inputs to layer 5 pyramidal neurons. , 2006, Cerebral cortex.

[41]  P. Castillo,et al.  Endocannabinoid-Mediated Metaplasticity in the Hippocampus , 2004, Neuron.

[42]  U. Kuhnt,et al.  Interaction between paired-pulse facilitation and long-term potentiation in area ca1 of guinea-pig hippocampal slices: Application of quantal analysis , 1994, Neuroscience.

[43]  D. Fortin,et al.  Brief trains of action potentials enhance pyramidal neuron excitability via endocannabinoid-mediated suppression of inhibition. , 2004, Journal of neurophysiology.

[44]  A. Polsky,et al.  Synaptic Integration in Tuft Dendrites of Layer 5 Pyramidal Neurons: A New Unifying Principle , 2009, Science.

[45]  Y. Dan,et al.  Spike timing-dependent plasticity: a Hebbian learning rule. , 2008, Annual review of neuroscience.

[46]  David Fernández de Sevilla,et al.  The Muscarinic Long-Term Enhancement of NMDA and AMPA Receptor-Mediated Transmission at Schaffer Collateral Synapses Develop through Different Intracellular Mechanisms , 2010, The Journal of Neuroscience.

[47]  G. Bi,et al.  Synaptic Modifications in Cultured Hippocampal Neurons: Dependence on Spike Timing, Synaptic Strength, and Postsynaptic Cell Type , 1998, The Journal of Neuroscience.

[48]  P. J. Sjöström,et al.  A Cooperative Switch Determines the Sign of Synaptic Plasticity in Distal Dendrites of Neocortical Pyramidal Neurons , 2006, Neuron.

[49]  Mu-ming Poo,et al.  The neurotrophin hypothesis for synaptic plasticity , 2000, Trends in Neurosciences.

[50]  J. Schiller,et al.  A Novel Form of Local Plasticity in Tuft Dendrites of Neocortical Somatosensory Layer 5 Pyramidal Neurons , 2016, Neuron.

[51]  T. Bliss,et al.  A synaptic model of memory: long-term potentiation in the hippocampus , 1993, Nature.

[52]  J. Schiller,et al.  NMDA spikes in basal dendrites of cortical pyramidal neurons , 2000, Nature.

[53]  Hugues Berry,et al.  Endocannabinoids mediate bidirectional striatal spike‐timing‐dependent plasticity , 2015, The Journal of physiology.

[54]  B. Alger,et al.  Postsynaptic spike firing reduces synaptic GABAA responses in hippocampal pyramidal cells , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[55]  Marco Fuenzalida,et al.  Changes of the EPSP Waveform Regulate the Temporal Window for Spike-Timing-Dependent Plasticity , 2007, The Journal of Neuroscience.

[56]  E. Levine,et al.  BDNF evokes release of endogenous cannabinoids at layer 2/3 inhibitory synapses in the neocortex. , 2010, Journal of neurophysiology.

[57]  Vivien Chevaleyre,et al.  Endocannabinoid-mediated synaptic plasticity in the CNS. , 2006, Annual review of neuroscience.

[58]  J. Clements.  A statistical test for demonstrating a presynaptic site of action for a modulator of synaptic amplitude , 1990, Journal of Neuroscience Methods.

[59]  A. Polsky,et al.  Properties of basal dendrites of layer 5 pyramidal neurons: a direct patch-clamp recording study , 2007, Nature Neuroscience.

[60]  E. Levine,et al.  Cannabinoid modulation of backpropagating action potential-induced calcium transients in layer 2/3 pyramidal neurons. , 2013, Cerebral cortex.

[61]  Livio Luongo,et al.  Endocannabinoids and neuropathic pain: focus on neuron–glia and endocannabinoid–neurotrophin interactions , 2014, The European journal of neuroscience.

[62]  Urit Gordon,et al.  Plasticity Compartments in Basal Dendrites of Neocortical Pyramidal Neurons , 2006, The Journal of Neuroscience.

[63]  J. Lisman.  Bursts as a unit of neural information: making unreliable synapses reliable , 1997, Trends in Neurosciences.

[64]  Johannes J. Letzkus,et al.  Learning Rules for Spike Timing-Dependent Plasticity Depend on Dendritic Synapse Location , 2006, The Journal of Neuroscience.

[65]  I. Soltesz,et al.  Distinct Endocannabinoid Control of GABA Release at Perisomatic and Dendritic Synapses in the Hippocampus , 2010, The Journal of Neuroscience.