title: Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons: distinctive sufficiency for hippocampus-dependent and amygdala-dependent synaptic and behavioral functions.
abstract: A major goal in current neuroscience is to understand the causal links connecting protein functions, neural activity, and behavior. The cannabinoid CB1 receptor is expressed in different neuronal subpopulations, and is engaged in fine-tuning excitatory and inhibitory neurotransmission. Studies using conditional knock-out mice revealed necessary roles of CB1 receptor expressed in dorsal telencephalic glutamatergic neurons in synaptic plasticity and behavior, but whether this expression is also sufficient for brain functions is still to be determined. We applied a genetic strategy to reconstitute full wild-type CB1 receptor functions exclusively in dorsal telencephalic glutamatergic neurons and investigated endocannabinoid-dependent synaptic processes and behavior. Using this approach, we partly restored the phenotype of global CB1 receptor deletion in anxiety-like behaviors and fully restored hippocampus-dependent neuroprotection from chemically induced epileptiform seizures. These features coincided with a rescued hippocampal depolarization-induced suppression of excitation (DSE), a CB1 receptor-dependent form of synaptic plasticity at glutamatergic neurons. By comparison, the rescue of the CB1 receptor on dorsal telencephalic glutamatergic neurons prolonged the time course of DSE in the amygdala, and impaired fear extinction in auditory fear conditioning. These data reveal that CB1 receptor in dorsal telencephalic glutamatergic neurons plays a sufficient role to control neuronal functions that are in large part hippocampus-dependent, while it is insufficient for proper amygdala functions, suggesting an unexpectedly complex circuit regulation by endocannabinoid signaling in the amygdala. Our data pave the way to a better understanding of neuronal networks in the context of behavior, by fine-tuned interference with synaptic transmission processes.
authors.affiliation: Institute of Physiological Chemistry, University Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Ruehle
authors.forename: Floor
authors.initials: F
authors.lastname: Remmers
authors.forename: Hector
authors.initials: H
authors.lastname: Romo-Parra
authors.forename: Federico
authors.initials: F
authors.lastname: Massa
authors.forename: Melanie
authors.initials: M
authors.lastname: Wickert
authors.forename: Simone
authors.initials: S
authors.lastname: Wörtge
authors.forename: Martin
authors.initials: M
authors.lastname: Häring
authors.forename: Nadine
authors.initials: N
authors.lastname: Kaiser
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marsicano
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Beat
authors.initials: B
authors.lastname: Lutz
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D001007:Anxiety / Q000523:psychology; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D055724:Electrophysiological Phenomena; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D018698:Glutamic Acid / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000633:toxicity; D008027:Light; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D060888:Real-Time Polymerase Chain Reaction; D043884:Receptor, Cannabinoid, CB1 / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D013687:Telencephalon / Q000166:cytology / Q000502:physiology*
chemical_list: D018690:Excitatory Amino Acid Agonists; D043884:Receptor, Cannabinoid, CB1; D018698:Glutamic Acid; D012313:RNA; D007608:Kainic Acid