Protein kinase C is essential for kainate-induced anxiety-related behavior and glutamatergic synapse upregulation in prelimbic cortex.

Abstract

Anxiety is one of common mood disorders, in which the deficit of serotonergic and GABAergic synaptic functions in the amygdala and prefrontal cortex is believed to be involved. The pathological changes at the glutamatergic synapses and neurons in these brain regions as well as their underlying mechanisms remain elusive, which we aim to investigate. An agonist of kainate-type glutamate receptors, kainic acid, was applied to induce anxiety-related behaviors. The morphology and functions of glutamatergic synapses in the prelimbic region of mouse prefrontal cortex were analyzed using cellular imaging and electrophysiology. After kainate-induced anxiety is onset, the signal transmission at the glutamatergic synapses is upregulated, and the dendritic spine heads are enlarged. In terms of the molecular mechanisms, the upregulated synaptic plasticity is associated with the expression of more protein kinase C (PKC) in the dendritic spines. Chelerythrine, a PKC inhibitor, reverses kainate-induced anxiety and anxiety-related glutamatergic synapse upregulation. The activation of glutamatergic kainate-type receptors leads to anxiety-related behaviors and glutamatergic synapse upregulation through protein kinase C in the prelimbic region of the mouse prefrontal cortex.