Liu et al. (2004) demonstrated that CRF and its related family of peptides act differentially at CRF1 versus CRF2 synaptic receptors to facilitate or depress excitatory transmission in CeA and lateral septum mediolateral nucleus. Notably, the effects of CRF and its ligands occurred without any apparent direct action on membrane potential or membrane excitability, suggesting that the role of CRF at these limbic synapses is that of a ‘neuroregulator’. The investigators suggested pre and postsynaptic loci for CRF1 and CRF2 receptors within the glutamatergic CeA and LSMN synapses. Although both synapses exhibit a comparable pre and postsynaptic location of CRF1 and CRF2 receptors, their functions (facilitation versus depression of glutamatergic transmission) are opposite within each synapse (Gallagher et al. 2008). Liu et al. (2004) also demonstrated that endogenous CRF ligands induce a tonic effect on excitatory glutamatergic transmission at synapses within both of these nuclei since application of competitive, selective CRF1 or CRF2 receptor antagonists resulted in an enhancement or depression of glutamatergic EPCS. A similar tonic endogenous action of CRF ligands was not observed under control conditions in the
