Stress Regulation of Sustained Attention and the Cholinergic Attention System

Abstract

Background: Stress exacerbates symptoms of schizophrenia and attention deficit hyperactivity disorder, which are characterized by impairments in sustained attention. Yet how stress regulates attention remains largely unexplored. Here we investigated whether a 6-day variable stressor (VS) altered sustained attention and the cholinergic attention system in male and female rats.Methods: Sustained attention was tested with the sustained attention task (SAT). Successful performance on SAT relies on the release of acetylcholine (ACh) into the cortex from cholinergic neurons in the nucleus basalis of Meynert (NBM). Thus, we evaluated whether VS altered the morphology of these neurons with a novel approach using a Cre-dependent virus in genetically modified ChAT::Cre rats, a species used for this manipulation only. Next, electrochemical recordings measured cortical ACh following VS. Finally, we used RNAseq to identify VS-induced transcriptional changes in the NBM.Results: VS impaired attentional performance in SAT and increased the dendritic complexity of NBM cholinergic neurons in both sexes. NBM cholinergic neurons are mainly under inhibitory control, so this morphological change could increase inhibition on these neurons, reducing downstream ACh release to impair attention. Indeed, VS decreased ACh release in the prefrontal cortex of males. Quantification of global transcriptional changes revealed that, although VS induced many sex-specific changes in gene expression, it increased several signaling molecules in both sexes.

Neurobiological Insights Into Stress-Induced Attention Deficit

“…Narrowing gaps in the current understanding of attentional control, Eck et al. ( 1 ) discovered that stress-induced attention deficits are linked with distinct neurobiological and molecular changes in major cortical regions.…”

“…In the current issue of Biological Psychiatry , Eck et al. ( 1 ) investigated the role of stress on the attention system in adult male and female rats. Variable stressors were administered via a daily episode of restraint, predator odor, or forced swim stressors for a total of 6 days.…”

“…Eck et al. ( 1 ) showed that variable stress reduced performance in a sustained attention test for both male and female rats. Dusp1 expression and hypertrophy of cholinergic dendrites were found in the nucleus basalis of Meynert for both sexes.…”

“…The authors performed several experiments to investigate how stress impacts neural functions of attention. They focused their investigation on the nucleus basalis of Meynert (NBM), which promotes attention through the activity of cholinergic neurons ( 1 ). The authors examined RNA expression of genes known to be associated with attention.…”

“…In nonstressed rats, Eck et al. ( 1 ) discovered that males have a higher baseline acetylcholine release than females. There are no sex differences in baseline attention, and therefore it is likely that further sex differences, such as increased nicotinic receptor density, may compensate for the decrease in cholinergic input in females.…”