Ionic and signaling mechanisms involved in neurotensin-mediated excitation of central amygdala neurons

Neurotensin (NT) serves as a neuromodulator in the brain where it regulates a variety of physiological functions. Whereas the central amygdala (CeA) expresses NT peptide and NTS1 receptors and application of NT has been shown to excite CeA neurons, the underlying cellular and molecular mechanisms have not been determined. We found that activation of NTS1 receptors increased the neuronal excitability of the lateral nucleus (CeL) of CeA. Both phospholipase C beta (pLc beta) and phosphatidylinositol 4,5-bisphosphate (PIP2) depletion were required, whereas intracellular Ca2+ release and PKC were unnecessary for NT-elicited excitation of CeL neurons. NT increased the input resistance and time constants of CeL neurons, suggesting that NT excites CeL neurons by decreasing a membrane conductance. Depressions of the inwardly rectifying K+ (Kir) channels including both the Kir2 subfamily and the GIRK channels were required for NT-elicited excitation of CeL neurons. Activation of NTS1 receptors in the CeL led to GABAergic inhibition of medial nucleus of CeA neurons, suggesting that NT modulates the network activity in the amygdala. Our results may provide a cellular and molecular mechanism to explain the physiological functions of NT in vivo.

Automated summary

Neurotensin (NT) acts as a neuromodulator in the brain, regulating various physiological functions. Activation of NTS1 receptors in the central amygdala leads to increased excitability of CeL neurons, involving phospholipase C beta (pLc beta) and phosphatidylinositol 4,5-bisphosphate (PIP2) depletion, but not intracellular Ca2+ release or PKC. NT excites CeL neurons by decreasing membrane conductance and inhibiting Kir channels, while also modulating network activity through GABAergic inhibition in the amygdala.