Diminished trkA receptor signaling reveals cholinergic-attentional vulnerability of aging (pages 278–293)
Vinay Parikh, William M. Howe, Ryan M. Welchko, Sean X. Naughton, Drew E. D'Amore, Daniel H. Han, Monika Deo, David L. Turner and Martin Sarter
Version of Record online: 11 DEC 2012 | DOI: 10.1111/ejn.12090
The cellular mechanisms underlying the exceptional vulnerability of the basal forebrain (BF) cholinergic neurons during pathological aging have remained elusive. Here we employed an adeno-associated viral vector-based RNA interference (AAV-RNAi) strategy to suppress the expression of trkA receptors by cholinergic neurons in the nucleus basalis of Meynert/substantia innominata (nMB/SI) of adult and aged rats. This study provides novel evidence that reduced trkA receptors is not sufficient to trigger cholinergic dysfunction. Rather, aging interacts with disrupted trkA signaling to escalate the vulnerability of BF cholinergic neurons and the manifestation of age-related attentional impairments.