Endocannabinoids facilitate the induction of LTP in the hippocampus

Exogenous cannabinoids disrupt behavioral learning and impede induction of long-term potentiation (LTP) in the hippocampus, yet endogenous cannabinoids (endocannabinoids) transiently suppress inhibitory post-synaptic currents (IPSCs) by activating cannabinoid CB1 receptors on GABAergic interneurons. We found that release of endocannabinoids by a rat CA1 pyramidal cell during this depolarization-induced suppression of inhibition (DSI) enabled a normally ineffective train of excitatory post-synaptic currents (EPSCs) to induce LTP in that cell, but not in neighboring cells. By showing that endocannabinoids facilitate LTP induction and help target LTP to single cells, these data shed new light on the physiological roles of endocannabinoids and may lead to a greater understanding of their effects on behavior and potential clinical use.

[1]  D. Wilkin,et al.  Neuron , 2001, Brain Research.

[2]  E. Kandel,et al.  Electrophysiology of hippocampal neurons. II. After-potentials and repetitive firing. , 1961, Journal of neurophysiology.

[3]  B. Alger,et al.  Calcium dependence of depolarization‐induced suppression of inhibition in rat hippocampal CA1 pyramidal neurons , 1999, The Journal of physiology.

[4]  Ken Mackie,et al.  Presynaptically Located CB1 Cannabinoid Receptors Regulate GABA Release from Axon Terminals of Specific Hippocampal Interneurons , 1999, The Journal of Neuroscience.

[5]  A. Marty,et al.  Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents , 1991, Neuron.

[6]  R. Tsien,et al.  Presynaptic enhancement shown by whole-cell recordings of long-term potentiation in hippocampal slices , 1990, Nature.

[7]  B. Alger,et al.  Transient suppression of GABAA-receptor-mediated IPSPs after epileptiform burst discharges in CA1 pyramidal cells. , 1998, Journal of neurophysiology.

[8]  M. Kano,et al.  Endogenous Cannabinoids Mediate Retrograde Signals from Depolarized Postsynaptic Neurons to Presynaptic Terminals , 2001, Neuron.

[9]  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.

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

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

[12]  T. Freund,et al.  Novel cannabinoid-sensitive receptor mediates inhibition of glutamatergic synaptic transmission in the hippocampus , 2001, Neuroscience.

[13]  H. Wigström,et al.  Facilitation of hippocampal long-lasting potentiation by GABA antagonists. , 1985, Acta physiologica Scandinavica.

[14]  Arne D. Ekstrom,et al.  NMDA Receptor Antagonism Blocks Experience-Dependent Expansion of Hippocampal “Place Fields” , 2001, Neuron.

[15]  J. Sullivan,et al.  Cellular and molecular mechanisms underlying learning and memory impairments produced by cannabinoids. , 2000, Learning & memory.

[16]  J. Wagner,et al.  Increased neuronal excitability during depolarization‐induced suppression of inhibition in rat hippocampus. , 1996, The Journal of physiology.