Acute vagus nerve stimulation enhances reversal learning in rats

Lindsay K-P Altidor; Matthew M Bruner; Josue F Deslauriers; Tyler S Garman; Saúl Ramirez; Elliott W Dirr; Kaitlynn P Olczak; Andrew P Maurer; Damon G Lamb; Kevin J Otto; Sara N Burke; Argyle V Bumanglag; Barry Setlow; Jennifer L Bizon

doi:10.1016/j.nlm.2021.107498

Acute vagus nerve stimulation enhances reversal learning in rats

Neurobiol Learn Mem. 2021 Oct:184:107498. doi: 10.1016/j.nlm.2021.107498. Epub 2021 Jul 29.

Affiliations

¹ Department of Neuroscience, University of Florida, Gainesville, FL, USA.
² J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA.
³ Department of Neuroscience, University of Florida, Gainesville, FL, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA; Engineering School of Sustainable Infrastructure and Environment, University of Florida, Gainesville, FL, USA.
⁴ Department of Neuroscience, University of Florida, Gainesville, FL, USA; Department of Psychiatry, University of Florida, Gainesville, FL, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA; Brain Rehabilitation Research Center, Malcom Randall VAMC, Gainesville, FL, USA.
⁵ Department of Neuroscience, University of Florida, Gainesville, FL, USA; J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA.
⁶ Department of Neuroscience, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA.
⁷ Department of Psychiatry, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA.
⁸ Department of Neuroscience, University of Florida, Gainesville, FL, USA; Evelyn F. & William L. McKnight Brain Institute, University of Florida, USA. Electronic address: bizonj@ufl.edu.

Abstract

Cognitive flexibility is a prefrontal cortex-dependent neurocognitive process that enables behavioral adaptation in response to changes in environmental contingencies. Electrical vagus nerve stimulation (VNS) enhances several forms of learning and neuroplasticity, but its effects on cognitive flexibility have not been evaluated. In the current study, a within-subjects design was used to assess the effects of VNS on performance in a novel visual discrimination reversal learning task conducted in touchscreen operant chambers. The task design enabled simultaneous assessment of acute VNS both on reversal learning and on recall of a well-learned discrimination problem. Acute VNS delivered in conjunction with stimuli presentation during reversal learning reliably enhanced learning of new reward contingencies. Enhancement was not observed, however, if VNS was delivered during the session but was not coincident with presentation of to-be-learned stimuli. In addition, whereas VNS delivered at 30 HZ enhanced performance, the same enhancement was not observed using 10 or 50 Hz. Together, these data show that acute VNS facilitates reversal learning and indicate that the timing and frequency of the VNS are critical for these enhancing effects. In separate rats, administration of the norepinephrine reuptake inhibitor atomoxetine also enhanced reversal learning in the same task, consistent with a noradrenergic mechanism through which VNS enhances cognitive flexibility.

Keywords: Cognitive flexibility; Reversal learning; Vagus nerve stimulation.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Adrenergic Uptake Inhibitors
Animals
Atomoxetine Hydrochloride / pharmacology
Baclofen / pharmacology
Conditioning, Operant / drug effects
Conditioning, Operant / physiology
Discrimination Learning / drug effects
Discrimination Learning / physiology
GABA-B Receptor Agonists / pharmacology
Male
Rats
Rats, Inbred BN
Reversal Learning* / drug effects
Reversal Learning* / physiology
Vagus Nerve Stimulation*

Substances

Adrenergic Uptake Inhibitors
GABA-B Receptor Agonists
Atomoxetine Hydrochloride
Baclofen

Grants and funding

T32 DK108736/DK/NIDDK NIH HHS/United States