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J Neurophysiol (April 1, 2003). 10.1152/jn.01037.2002
Submitted on Submitted 15 November 2002; accepted in final form 22 December 2002
REPORT
Pyramidal Neuron Synapses of the Neocortex
Department of Pharmacology and Program in Neuroscience, University of Connecticut Health Center, Farmington, Connecticut 06030
Trettel, Joseph and
Eric
S. Levine.
Endocannabinoids Mediate Rapid Retrograde Signaling At
Interneuron Pyramidal Neuron Synapses of the Neocortex. J. Neurophysiol. 89: 2334-2338, 2003. In the
neocortex, inhibitory interneurons tightly regulate the firing patterns
and integrative properties of pyramidal neurons (PNs). The
endocannabinoid system of the neocortex may play an important role in
the activity-dependent regulation of inhibitory (i.e., GABAergic)
inputs received by PNs. In the present study, using whole cell
recordings from layer 2/3 PNs in slices of mouse sensory cortex, we
have identified a role for PN-derived endocannabinoids in the control
of afferent inhibitory strength. Pairing evoked inhibitory currents
with repeated epochs of postsynaptic depolarization led to a transient
suppression of inhibition that was induced by a rise in postsynaptic
Ca2+ and was expressed as a reduction in
presynaptic GABA release. An antagonist (AM251) of the type-1
cannabinoid receptor blocked the depolarization-induced suppression of
evoked inhibitory postsynaptic currents (eIPSCs), and the cannabinoid
WIN55,212-2 reduced eIPSC amplitude and occluded suppression. The
degree of WIN55,212-2-mediated inhibition of eIPSCs was strongly
correlated with the magnitude of depolarization-induced suppression of
the eIPSCs, suggesting that the WIN-sensitive afferents are suppressed
by PN depolarization. Moreover, blocking endocannabinoid uptake with
AM404 strongly modulated the kinetics and magnitude of eIPSC
suppression. We conclude that the release of endocannabinoids from PNs
allows for the postsynaptic control of presynaptic inhibition and could have profound consequences for the integrative properties of
neocortical PNs.
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