An inhibitory pathway controlling the gating mechanism of the mouse lateral amygdala revealed by voltage-sensitive dye imaging

The lateral amygdala nucleus (La) is known as a gateway for emotional learning that interfaces sensory inputs from the cortex and the thalamus. In the La, inhibitory GABAergic inputs control the strength of sensory inputs and interfere with the initial step of the acquisition of fear memory. In the present study, we investigated the spatial and temporal patterns of the inhibitory responses in mouse La using voltage-sensitive dye imaging. Stimulating the external capsule (EC) induced large and long-lasting hyperpolarizing signals in the La. We focused on these hyperpolarizing signals, revealing the origins of the inhibitory inputs by means of surgical cuts on the possible afferent pathways with four patterns. Isolating the medial branch of EC (ECmed), but not the lateral branch of EC (EClat), from the La strongly suppressed the induction of the hyperpolarization. Interestingly, isolating the ECmed from the caudate putamen did not suppress the hyperpolarization, while the surgical cut of the ECmed fiber tract moderately suppressed it. Glutamatergic antagonists completely suppressed the hyperpolarizing signals induced by the stimulation of EC. When directly stimulating the dorsal, middle or ventral part of the ECmed fiber tract in the presence of glutamatergic antagonists, only the stimulation in the middle part of the ECmed caused hyperpolarization. These data indicate that the GABAergic neurons in the medial intercalated cluster (m-ITC), which receive glutamatergic excitatory input from the ECmed fiber tract, send inhibitory afferents to the La. This pathway might have inhibitory effects on the acquisition of fear memory.