Systematic comparison of intrinsic membrane properties of locus coeruleus neurons in Mecp2‐null and wild‐type mice

Abstract

Rett syndrome caused by mutations in MECP2 (Methyl‐CpG binding protein 2) gene shows autonomic abnormalities, in which brainstem norepinephrinergic (NE) systems are involved. To determine if the Mecp2 defect affects intrinsic membrane properties of locus coeruleus (LC) NE neurons, whole‐cell current clamp was performed in brain slices of 3‐4 weeks old Mecp2‐/y and wild‐type mice. Of 102 neurons studied, no statistical differences were found in passive membrane properties except the time constant that was significantly smaller in Mecp2‐/y neurons. Most LC neurons in both groups displayed spontaneous firing activity. The action potential duration was prolonged in Mecp2‐/y mice due to an extended rising phase. Voltage clamp in acutely dissociated LC neurons confirmed that the density of voltage‐activated Na+ currents was reduced in Mecp2‐/y mice. Mecp2 knockout produced a negative shift of half inactivation potential of delayed excitation, and had rather small effect on spike frequency adaption. The overall amplitude of afterhyperpolarization (AHP) was lower in Mecp2‐/y neurons with a clear manifestation of the fast AHP. No evident bursting activity and post‐inhibition rebound was observed in both groups. The electrophysiological abnormalities of LC NE neurons involving likely defects in Na+ and K+ channels seem to contribute to the autonomic dysfunction in Mecp2‐/y mice. (supported by NIH R01‐HL067890)