Age-related changes in basal forebrain afferent activation in response to food paired stimuli

The basal forebrain contains a phenotypically-diverse assembly of neurons, including those using acetylcholine as their neurotransmitter. This basal forebrain cholinergic system projects to the entire neocortical mantle as well as subcortical limbic structures that include the hippocampus and amygdala. Basal forebrain pathology, including cholinergic dysfunction, is thought to underlie the cognitive impairments associated with several age-related neurodegenerative conditions, including Alzheimer's disease. Basal forebrain dysfunction may stem, in part, from a failure of normal afferent regulation of cholinergic and other neurons in this area. However, little is understood regarding how aging, alone, affects the functional regulation of basal forebrain afferents in the context of motivated behavior. Here, we used neuronal tract-tracing combined with motivationally salient stimuli in an aged rodent model to examine how aging alters activity in basal forebrain inputs arising from several cortical, limbic and brainstem structures. Young rats showed greater stimulus-associated activation of basal forebrain inputs arising from prelimbic cortex, nucleus accumbens and the ventral tegmental area compared with aged rats. Aged rats also showed increased latency to respond to palatable food presentation compared to young animals. Changes in activation of intrinsic basal forebrain cell populations or afferents were also observed as a function of age or experimental condition. These data further demonstrate that age-related changes in basal forebrain activation and related behavioral and cognitive functions reflect a failure of afferent regulation of this important brain region.