Altered short-term and long-term plasticity in the dentate gyrus in mice lacking the cannabinoid CB1 receptor

Abstract

We investigated short-term and long-term plasticity characteristics in vivo in a mutant mouse with a targeted disruption of the endocannabinoid CB1 receptor gene (Marsicano et al., 2002). In isoflurane anaesthetised mice, perforant path stimulation evokes both a field excitatory postsynaptic potential (fEPSP) and a population-spike potential (pop-spike) from the hippocampal dentate gyrus. No differences between wild-type and knock-out animals were found in paired-pulse facilitation of fEPSP amplitudes, a measure of presynaptic short-term plasticity. With paired-pulse stimulation of population-spike, a measure of polysynaptic inhibitory feedback within the dentate gyrus, no differences were found for paired-pulse depression with inter-pulse intervals (IPIs) up to 30 ms, but a decreased paired-pulse facilitation was found in the knock-out animals with IPIs ranging from 40–100 ms. Potentiation of fEPSP and pop-spike, following tetanic stimulation of the perforant path, was significantly more pronounced in the CB1-deficient mice compared to the wild-type littermates. These findings suggest a role of the CB1-R in synaptic plasticity in vivo. We are currently investigating by means of conditional knock-outs that lack expression of CB1 specifically in principal or in interneurons, whether this phenomenon is due to enhanced glutamatergic or decreased GABAergic transmission in the hippocampus.