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This Article Full Text Full Text (PDF) Supplemental Figures All Versions of this Article: 101/5/2434    most recent 00047.2009v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Zhao, Y. Articles by Tzounopoulos, T. Search for Related Content PubMed PubMed Citation Articles by Zhao, Y. Articles by Tzounopoulos, T.

Distinct Functional and Anatomical Architecture of the Endocannabinoid System in the Auditory Brainstem

¹Department of Otolaryngology, ²Department of Neurobiology, University of Pittsburgh School of Medicine and ³Center for the Neural Basis of Cognition, University of Pittsburgh and Carnegie Mellon, Pittsburgh, Pennsylvania; and ⁴Department of Physiology and Neurobiology, University of Connecticut, Storrs, Connecticut

Submitted 15 January 2009; accepted in final form 9 March 2009

Endocannabinoids (ECs) act as retrograde messengers that enable postsynaptic cells to regulate the strength of their synaptic inputs. Here, by using physiological and histological techniques, we showed that, unlike in other parts of the brain, excitatory inputs are more sensitive than inhibitory inputs to EC signaling in the dorsal cochlear nucleus (DCN), an auditory brainstem nucleus. The principal cells of the DCN, fusiform cells, integrate acoustic signals through nonplastic synapses located in the deep layer with multimodal sensory signals carried by plastic parallel fibers in the molecular layer. Parallel fibers contact fusiform cells and inhibitory interneurons, the cartwheel cells, which in turn inhibit fusiform cells. Postsynaptic depolarization or pairing of postsynaptic potentials (PSPs) with action potentials (APs) induced EC-mediated modulation of excitatory inputs but did not affect inhibitory inputs. Quantitative electron microscopical studies showed that glutamatergic terminals express more cannabinoid 1 receptors (CB1Rs) than glycinergic terminals. Fusiform and cartwheel cells express diacylglycerol lipase and β (DGL/β), the two enzymes involved in the generation of the EC, 2-arachidonoyl-glycerol (2-AG). DGL and DGLβ are found in the spines of cartwheel but not fusiform cells indicating that the synthesis of ECs is more distant from parallel fiber synapses in fusiform than cartwheel cells. The differential localization and density of DGL/β and CB1Rs leads to cell- and input-specific EC signaling that favors activity-dependent EC-mediated suppression at synapses between parallel fibers and cartwheel cell spines, thus leading to reduced feedforward inhibition in fusiform cells. We propose that EC signaling is a major modulator of the balance of excitation and inhibition in auditory circuits.