Hyperexcitability of amygdala neurons of senescence-accelerated mouse revealed by electrical and optical recordings in an in vitro slice preparation

In the amygdala (AMG) slices obtained from both the young (4-7 months old) and aged (17-20 months old) groups of Senescence-Accelerated Mouse (SAM) P10, spontaneous bursts were recorded in the medial, central and basolateral nuclei. The spontaneous bursts were also observed in the slices from the young group of SAMR1, whereas the mean frequency was significantly lower than that from the young group of SAMP10. The spontaneous burst was barely detectable in slices from the aged group of SAMR1 during perfusing with the standard solution, while bicuculline methiodide (10 μM), a GABA(A) receptor antagonist, or Mg²⁺-free solution induced a similar bursting activity observed in the young group. The burst response was also evoked in the medial, central and basolateral AMG following stimulation of the stria terminalis (ST). Both spontaneous and evoked bursts were completely suppressed by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 4 μM), an α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor antagonist, but not by (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]- cyclohepten-5,10-imine hydrogen maleate (MK-801, 30 μM), an N-methyl-D- aspartate receptor antagonist. The hyperexcitability of the AMG neurons was further substantiated by optical recordings. Following stimulation of the ST, the optical signals reflected postsynaptic responses spread into the medial and central AMG areas at 2-5 ms and faded out at 20-30 ms after stimulation. The intensity of the optical signal recorded in the slice from the young SAMP10 was significantly higher than that from SAMR1 or ddY mice. These observations indicate that bursts mediated by AMPA/kainate receptors were transiently generated in the AMG of SAMR1 at the young age, while the bursts with higher frequency were continuously generated in the AMG of SAMP10. The chronic neuronal hyperactivity in the AMG may be partially responsible for the age-related deterioration of memory and learning abilities observed in SAMP10.