Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons: distinctive sufficiency for hippocampus-dependent and amygdala-dependent synaptic and behavioral functions.
Journal of Neuroscience. 2013-06-19; 33(25): 10264-10277
DOI: 10.1523/jneurosci.4171-12.2013
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1. J Neurosci. 2013 Jun 19;33(25):10264-77. doi: 10.1523/JNEUROSCI.4171-12.2013.
Cannabinoid CB1 receptor in dorsal telencephalic glutamatergic neurons:
distinctive sufficiency for hippocampus-dependent and amygdala-dependent synaptic
and behavioral functions.
Ruehle S(1), Remmers F, Romo-Parra H, Massa F, Wickert M, Wörtge S, Häring M,
Kaiser N, Marsicano G, Pape HC, Lutz B.
Author information:
(1)Institute of Physiological Chemistry, University Medical Center of the
Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
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.
DOI: 10.1523/JNEUROSCI.4171-12.2013
PMID: 23785142 [Indexed for MEDLINE]