Anxiety-associated network asynchrony and GABAergic synapse attenuation

in amygdala are improved by mGluR1,5 activation

Jin-Hui Wang

Institute of Biophysics, Chinese Academy of Sciences, Beijing China 100101

Anxiety, personified as unstable mood, elevated attention, negative interpretation and social phobia under the conditions of potential threatening signs, is one of prevalent psychological disorders, in which the atypical expression of certain genes and the abnormality of amygdala are presumably involved. The intermediate processes between the genetic deficits and anxiety disorders, such as the pathological characteristics of amygdala neuronal networks, remain unclear. The improvement of such pathogenesis by pharmacological approach needs to be explored. DBA/2 mice with genetic variance and anxiety phenotype were applied in our studies. By combining behavioral task with two-photon cellular imaging and electrophysiology, we investigated the dynamics of neuronal networks in basolateral amygdala as well as the effect of metabotropic glutamate receptor (mGluR) activation on pathological network. The temporal correlation of network cells, the excitability of neurons and the transmission of GABAergic synapses were comparatively analyzed. Amygdala neurons in DBA/2 mice show asynchronous activity and variable excitability, as well as GABAergic synapses transmit signals weakly, compared with those in low anxiety FVB/N mice. mGluR1,5 activation by 3,5-DHPG improves the anxiety-like behavior of DBA/2 mice, synchronizes the activity of amygdala neurons and strengthens the signal transmission at GABAergic synapses. Therefore, neuronal network asynchrony and GABAergic synapse attenuation in amygdala are involved in anxiety, which are improved by mGluR1,5 activation.