Kurzfassung

Teilprojekt A04: Dynamics and receptor function of the endocannabinoid system in fear circuits
The modulatory role of endocannabinoids (eCB) on neurotransmission puts this signalling system into
an ideal position to fine-tune fear responses. In the first funding period, we (i) demonstrated regional
and functional specificity of eCB signalling in the amygdala related to fear extinction, (ii) generated a
new mutant mouse line with a silenced CB1 receptor gene as a default state, but with the...Teilprojekt A04: Dynamics and receptor function of the endocannabinoid system in fear circuits
The modulatory role of endocannabinoids (eCB) on neurotransmission puts this signalling system into
an ideal position to fine-tune fear responses. In the first funding period, we (i) demonstrated regional
and functional specificity of eCB signalling in the amygdala related to fear extinction, (ii) generated a
new mutant mouse line with a silenced CB1 receptor gene as a default state, but with the ability to reactivate CB1 receptor gene expression in a region- and cell type-specific manner using Cre
recombinase, and (iii) obtained first data indicating that the CB1 receptor in glutamatergic neurons is
essential, but not sufficient for wild-type eCB signalling in the amygdala, in order to provide wild-type
fear extinction. These results put us in a position to identify necessary CB1 receptor functions by
genetic inactivation of the CB1 receptor gene in defined areas of the (extended) amygdala by AAV-Cre injections into CB1floxed/floxed mice, and to assess sufficient functions of the CB1 receptor by genetic reactivation separately and in combination, respectively, in glutamatergic and GABAergic neurons.
Furthermore, we will test the hypothesis whether eCB availability controlled by enzymatic synthesis
and degradation is critically involved in the regulation of anxiety and conditioned fear. We will
experimentally interfere with the levels of eCBs with regional specificity, making use of the viral
techniques and the established behavioural paradigms combined with electrophysiological analyses of synaptic plasticity ex vivo. Our project aims at integrating this lipid signalling system into central fearcircuits (amygdala-PFC-BNST) and the major behavioural out-puts of fear extinction and sustained fear» weiterlesen» einklappen