QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, October 12, 2005, 25(41):9449-9459; doi:10.1523/JNEUROSCI.2078-05.2005

This Article Full Text Full Text (PDF) Supplemental data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (9) Citing Articles via Google Scholar Google Scholar Articles by Heinbockel, T. Articles by Kao, J. P. Y. Search for Related Content PubMed PubMed Citation Articles by Heinbockel, T. Articles by Kao, J. P. Y.

 Previous Article  |  Next Article 

Cellular/Molecular
Endocannabinoid Signaling Dynamics Probed with Optical Tools

Thomas Heinbockel,^1,2 * Darrin H. Brager,^1 * Christian G. Reich,¹ Jun Zhao,³ Sukumaran Muralidharan,³ Bradley E. Alger,^1,2 and Joseph P. Y. Kao^1,2,3

¹Department of Physiology, ²Program in Neuroscience, University of Maryland School of Medicine, and ³Medical Biotechnology Center, University of Maryland Biotechnology Institute, Baltimore, Maryland 21201

Intercellular signaling dynamics critically influence the functional roles that the signals can play. Small lipids are synthesized and released from neurons, acting as intercellular signals in regulating neurotransmitter release, modulating ion channels on target cells, and modifying synaptic plasticity. The repertoire of biological effects of lipids such as endocannabinoids (eCBs) is rapidly expanding, yet lipid signaling dynamics have not been studied. The eCB system constitutes a powerful tool for bioassaying the dynamics of lipid signaling. The eCBs are synthesized in, and released from, postsynaptic somatodendritic domains that are readily accessible to whole-cell patch electrodes. The dramatic effects of these lipid signals are detected electrophysiologically as CB1-dependent alterations in conventional synaptic transmission, which therefore serve as a sensitive reporter of eCB actions. We used electrophysiological recording, photolytic release of caged glutamate and a newly developed caged AEA (anandamide), together with rapid [Ca²⁺]_i measurements, to investigate the dynamics of retrograde eCB signaling between CA1 pyramidal cells and GABAergic synapses in rat hippocampus in vitro. We show that, at 22°C, eCB synthesis and release must occur within 75-190 ms after the initiating stimulus, almost an order of magnitude faster than previously thought. At 37°C, the time could be <50 ms. Activation of CB1 and downstream processes constitute a significant fraction of the total delay and are identified as major rate-limiting steps in retrograde signaling. Our findings imply that lipid messenger dynamics are comparable with those of metabotropic neurotransmitters and can modulate neuronal interactions on a similarly fast time scale.

Key words: anandamide; metabotropic glutamate; calcium; photolysis; GABA; endocannabinoid

---

Received May 23, 2005; revised August 29, 2005; accepted August 30, 2005.

This article has been cited by other articles:

				E. Carter and X.-J. Wang Cannabinoid-Mediated Disinhibition and Working Memory: Dynamical Interplay of Multiple Feedback Mechanisms in a Continuous Attractor Model of Prefrontal Cortex Cereb Cortex, September 1, 2007; 17(suppl_1): i16 - i26. [Abstract] [Full Text] [PDF]

				V. A. Bender, K. J. Bender, D. J. Brasier, and D. E. Feldman Two coincidence detectors for spike timing-dependent plasticity in somatosensory cortex. J. Neurosci., April 19, 2006; 26(16): 4166 - 4177. [Abstract] [Full Text] [PDF]

				S. M. Thompson, J. P. Y. Kao, R. H. Kramer, K. E. Poskanzer, R. A. Silver, D. Digregorio, and S. S.-H. Wang Flashy Science: Controlling Neural Function with Light J. Neurosci., November 9, 2005; 25(45): 10358 - 10365. [Full Text] [PDF]

				B. E. Alger Endocannabinoid Identification in the Brain: Studies of Breakdown Lead to Breakthrough, and There May Be NO Hope Sci. Signal., November 8, 2005; 2005(309): pe51 - pe51. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help