TY - JOUR
T1 - Requirement for CB1 but not GABAB receptors in the cholecystokinin mediated inhibition of GABA release from cholecystokinin expressing basket cells
AU - Lee, Sang Hun
AU - Soltesz, Ivan
PY - 2011/2
Y1 - 2011/2
N2 - Cholecystokinin (CCK) is an abundant neuropeptide involved in normal behaviour and pathophysiological conditions. Recently, CCK was shown to act as a molecular switch for perisomatic inhibition in the hippocampus, by directly depolarizing parvalbumin expressing (PV+) basket cells while indirectly depressing GABA release from CCK expressing (CCK+) basket cells. However, whether these two CCK-mediated effects are causally related is controversial, with one hypothesis proposing that the CCK-induced firing of PV+ basket cells increases the release of GABA, which, in turn, heterosynaptically inhibits GABA release from neighbouring CCK+ basket cell terminals through presynaptic GABAB receptors. Our present data from paired recording experiments from presynaptic basket cells and postsynaptic CA1 pyramidal cells in acute rat brain slices show that the P/Q Ca2+ channel antagonist agatoxin TK (250 nm) abolished GABA release from PV+ basket cells, but it had no effect on the CCK-induced depression of GABA release from CCK+ basket cells. Furthermore, CCK decreased GABA release from CCK+ basket cells even in the presence of the GABAB receptor antagonist CGP55845 (2 μm). In contrast, cannabinoid type-1 (CB1) receptor blockade with AM251 (10 μm) prevented the action of CCK on GABA release both from CCK+ basket cells and dendritically projecting, CCK+ Schaffer collateral-associated interneurons. These results demonstrate that CCK-mediated inhibition of GABA release from CCK+ cells requires no cross-talk between PV+ and CCK+ synapses, but that it critically depends on CB1 receptor-mediated endocannabinoid signalling at both perisomatic and dendritic inputs.
AB - Cholecystokinin (CCK) is an abundant neuropeptide involved in normal behaviour and pathophysiological conditions. Recently, CCK was shown to act as a molecular switch for perisomatic inhibition in the hippocampus, by directly depolarizing parvalbumin expressing (PV+) basket cells while indirectly depressing GABA release from CCK expressing (CCK+) basket cells. However, whether these two CCK-mediated effects are causally related is controversial, with one hypothesis proposing that the CCK-induced firing of PV+ basket cells increases the release of GABA, which, in turn, heterosynaptically inhibits GABA release from neighbouring CCK+ basket cell terminals through presynaptic GABAB receptors. Our present data from paired recording experiments from presynaptic basket cells and postsynaptic CA1 pyramidal cells in acute rat brain slices show that the P/Q Ca2+ channel antagonist agatoxin TK (250 nm) abolished GABA release from PV+ basket cells, but it had no effect on the CCK-induced depression of GABA release from CCK+ basket cells. Furthermore, CCK decreased GABA release from CCK+ basket cells even in the presence of the GABAB receptor antagonist CGP55845 (2 μm). In contrast, cannabinoid type-1 (CB1) receptor blockade with AM251 (10 μm) prevented the action of CCK on GABA release both from CCK+ basket cells and dendritically projecting, CCK+ Schaffer collateral-associated interneurons. These results demonstrate that CCK-mediated inhibition of GABA release from CCK+ cells requires no cross-talk between PV+ and CCK+ synapses, but that it critically depends on CB1 receptor-mediated endocannabinoid signalling at both perisomatic and dendritic inputs.
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U2 - 10.1113/jphysiol.2010.198499
DO - 10.1113/jphysiol.2010.198499
M3 - Article
C2 - 21173082
AN - SCOPUS:79951701420
SN - 0022-3751
VL - 589
SP - 891
EP - 902
JO - Journal of Physiology
JF - Journal of Physiology
IS - 4
ER -