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J Neurophysiol (June 28, 2006). doi:10.1152/jn.00310.2006
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Submitted on March 22, 2006
Accepted on June 22, 2006

Endocannabinoid mediated depolarization-induced suppression of inhibition in hilar mossy cells of the rat dentate gyrus

Mackenzie E. Hofmann1, Ben Nahir2, and Charles J. Frazier3*

1 Department of Pharmacodynamics, University of Florida, Gainesville, Florida, United States
2 Department of Neuroscience, University of Florida, Gainesville, Florida, United States
3 Department of Pharmacodynamics, University of Florida, Gainesville, Florida, United States; Department of Neuroscience, University of Florida, Gainesville, Florida, United States

* To whom correspondence should be addressed. E-mail: cjfraz{at}ufl.edu.

Hilar mossy cells represent a unique population of local circuit neurons in the hippocampus and dentate gyrus. Here we use electrophysiological techniques in acute preparations of hippocampal slices to demonstrate that depolarization of a single hilar mossy cell can produce robust inhibition of local GABAergic afferents. This depolarization induced suppression of inhibition (DSI) can be observed as a transient reduction in frequency of spontaneous inhibitory postsynaptic currents (sIPSCs), or as a transient reduction in amplitude of evoked IPSCs. We find that DSI of evoked IPSCs as observed in hilar mossy cells is enhanced by activation of muscarinic acetylcholine receptors, blocked by chelation of postsynaptic calcium, and critically dependent on retrograde activation of presynaptic cannabinoid (CB1) receptors. We further report that activation of CB1 receptors on GABAergic afferents to hilar mossy cells (by either endogenous or exogenous agonists) preferentially inhibits calcium dependent exocytosis, and that endocannabinoid dependent retrograde signalling in this system is subject to tight spatial constraints.




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