Increased intrinsic excitability and decreased synaptic inhibition in aged somatosensory cortex pyramidal neurons

Abstract

Sensorimotor performance declines during advanced age, partially due to deficits in somatosensory acuity. Cortical receptive field expansion contributes to somatosensory deficits, suggesting increased excitability or decreased inhibition in primary somatosensory cortex (S1) pyramidal neurons. To ascertain changes in excitability and inhibition, we measured both properties in neurons from vibrissal S1 in brain slices from young and aged mice. Because adapting and non-adapting neurons-the principal pyramidal types in layer 5 (L5)-differ in intrinsic properties and inhibitory inputs, we determined age-dependent changes according to neuron type. We found an age-dependent increase in intrinsic excitability in adapting neurons, caused by a decrease in action potential threshold. Surprisingly, in non-adapting neurons we found both an increase in excitability caused by increased input resistance, and a decrease in synaptic inhibition. Spike frequency adaptation, already small in non-adapting neurons, was further reduced by aging, whereas sag, a manifestation of I_h, was increased. Therefore, aging caused both decreased inhibition and increased intrinsic excitability, but these effects were specific to pyramidal neuron type.

Keywords: Action potential threshold; Aging; Barrel cortex; Critical frequency; GABA; Hyperexcitability; Inhibition; Input resistance; Intrinsic excitability; Layer 5; Somatosensory cortex; Spike frequency adaptation; sag.