466 G. Riedel and S.N. Davies
(100 Hz for 200 ms), but also that it blocked LTD induced by lower frequency
stimulation (1 Hz for 15 min). This block of LTD was again relieved by reducing
the concentration of Mg2+in the perfusion medium, or by slightly depolarising
the recorded cell during the low-frequency train. It was therefore interpreted as
being secondary to a reduced excitatory drive resulting in any postsynaptic Ca2+
changes being insufficient to reach threshold to induce LTD.
There is also intriguing evidence that release of endogenous cannabinoids may
contribute to the maintenance of LTD of IPSCs, and hence contribute to the E–S
coupling that is observed after the induction of LTP. High-frequency stimulation
(100 Hz for 1 s) or theta burst stimulation (10x100 Hz for 50 ms) caused LTD of
pharmacologicallyisolatedIPSCsrecordedfromtheCA1regionofrathippocampal
slices (Chevaleyre and Castillo 2003). AM251 blocked the induction of this LTD,
but had no effect if it was applied 10 min after the high-frequency train. LTD was
blocked by group I mGlu receptor antagonists, and mimicked by group I mGlu
receptor agonists. This suggests that activation of group I mGlu receptors during
the high- frequency train stimulates transient release of an endocannabinoid that
causes a persistent reduction of GABA release. In this scenario, endocannabinoids
have a role, not only in regulating the induction of synaptic plasticity, but also in
the expression of synaptic plasticity, during the maintenance phase. Specifically,
they may contribute to the increased E–S potentiation, i.e. the ability of a given-
sized EPSP to evoke an action potential. The mechanism by which transient release
of an endocannabinoid can evoke long-lasting depression of the IPSC has not been
determined.
5.3
LTP and LTD in Other Brain Regions
The differences in expression of CB 1 receptorsinvariousbrainregionssuggest
that cannabinoid receptor ligands may have different effects on synaptic plasticity
in different synaptic pathways.
5.3.1
Cortex
Results from prefrontal cortex are generally consistent with those from the hip-
pocampus, but carry the same caveat that they may reflect activity of cannabinoids
at TRPV1-like receptors, rather than CB 1 receptors. High-frequency stimulation
(100 Hz for 1 s) induced LTD, LTP, or no change in pharmacologically isolated
EPSCs in approximately equal proportions of cells recorded. WIN55,212-2 (1 μM)
increased the proportion of cells exhibiting LTD and decreased the proportion
exhibiting LTP, whereas rimonabant increased the proportion of cells exhibiting
LTP and decreased the proportion exhibiting LTD (Auclair et al. 2000; Barbara et
al. 2003). These effects on synaptic plasticity could be explained as a secondary
consequence of changes in the baseline EPSC, since WIN55,212-2 decreased, and