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J Neurosci. 2015 Mar 4;35(9):3842-50. doi: 10.1523/JNEUROSCI.3167-14.2015.

Cannabinoid CB1 receptor calibrates excitatory synaptic balance in the mouse hippocampus.

Author information

1
Institute of Physiological Chemistry, Medical Center of the Johannes Gutenberg University Mainz, 55128 Mainz, Germany.
2
Zoological Institute, Division Cellular Neurobiology, 38106 Braunschweig, Germany, and.
3
Zoological Institute, Division Cellular Neurobiology, 38106 Braunschweig, Germany, and AG NIND, HZI, D-38124 Braunschweig, Germany.
4
Zoological Institute, Division Cellular Neurobiology, 38106 Braunschweig, Germany, and AG NIND, HZI, D-38124 Braunschweig, Germany m.korte@tu-bs.de.

Abstract

The endocannabinoid system negatively regulates the release of various neurotransmitters in an activity-dependent manner, thereby influencing the excitability of neuronal circuits. In the hippocampus, cannabinoid type 1 (CB1) receptor is present on both GABAergic and glutamatergic axon terminals. CB1 receptor-deficient mice were previously shown to have increased hippocampal long-term potentiation (LTP). In this study, we have investigated the consequences of cell-type-specific deletion of the CB1 receptor on the induction of hippocampal LTP and on CA1 pyramidal cell morphology. Deletion of CB1 receptor in GABAergic neurons in GABA-CB1-KO mice leads to a significantly decreased hippocampal LTP compared with WT controls. Concomitantly, CA1 pyramidal neurons have a significantly reduced dendritic branching both on the apical and on the basal dendrites. Moreover, the average spine density on the apical dendrites of CA1 pyramidal neurons is significantly diminished. In contrast, in mice lacking CB1 receptor in glutamatergic cells (Glu-CB1-KO), hippocampal LTP is significantly enhanced and CA1 pyramidal neurons show an increased branching and an increased spine density in the apical dendritic region. Together, these results indicate that the CB1 receptor signaling system both on inhibitory and excitatory neurons controls functional and structural synaptic plasticity of pyramidal neurons in the hippocampal CA1 region to maintain an appropriate homeostatic state upon neuronal activation. Consequently, if the CB1 receptor is lost in either neuronal population, an allostatic shift will occur leading to a long-term dysregulation of neuronal functions.

KEYWORDS:

CB1 receptor; LTP; cannabinoids; dendritic morphology; spines; synaptic plasticity

PMID:
25740514
DOI:
10.1523/JNEUROSCI.3167-14.2015
[Indexed for MEDLINE]
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