Differential effects of cholinergic lesions on dendritic spines in frontal cortex of young adult and aging rats.

Previously, we demonstrated that plasticity of frontal cortex is altered in aging rats: cholinergic lesions of the nucleus basalis magnocellularis (NBM) produce larger declines in dendritic morphology in frontal cortex of middle-aged and aged rats relative to young adults. To more closely examine the interactive effects of age and cholinergic deafferentation on synaptic connectivity in frontal cortex, we assessed the effects of specific cholinergic lesions on spine density of frontal cortical neurons in young adult, middle-aged, and aged rats. Rats received unilateral sham or 192 IgG-saporin lesions of the NBM. Two weeks after surgery, brains were stained using a Golgi-Cox procedure, and spine density was quantified in second-, third-, and fourth-order basilar dendrites of pyramidal neurons in layer II-III of frontal cortex. Spine density was reduced at all branch orders in aged, sham-lesioned rats. In addition, whereas lesions produced a marked increase in spine density on second- and third-order branches in young adult rats, lesions failed to significantly alter spine density in middle-aged and aged rats. Thus, the upregulation of dendritic spines may be a compensatory response to deafferentation, which is lost with advancing age.