title: Repeated Nicotine Strengthens Gamma Oscillations in the Prefrontal Cortex and Improves Visual Attention.
abstract: Nicotine has strong addictive as well as procognitive properties. While a large body of research on nicotine continues to inform us about mechanisms related to its reinforcing effects, less is known about clinically relevant mechanisms that subserve its cognitive-enhancing properties. Understanding the latter is critical for developing optimal strategies for treating cognitive deficits. The primary brain region implicated in cognitive functions improved by nicotine is the prefrontal cortex (PFC). Here we assessed the impact of nicotine on unit activity and local field potential oscillations in the PFC of behaving rats. An acute dose of nicotine produced a predominantly inhibitory influence on population activity, a small increase in gamma oscillations, and a decrease in theta and beta oscillations. After a daily dosing regimen, a shift to excitatory-inhibitory balance in single-unit activity and stronger gamma oscillations began to emerge. This pattern of plasticity was specific to the gamma band as lower frequency oscillations were suppressed consistently across daily nicotine treatments. Gamma oscillations are associated with enhanced attentional capacity. Consistent with this mechanism, the repeat dosing regimen in a separate cohort of subjects led to improved performance in an attention task. These data suggest that procognitive effects of nicotine may involve development of enhanced gamma oscillatory activity and a shift to excitatory-inhibitory balance in PFC neural activity. In the context of the clinical use of nicotine and related agonists for treating cognitive deficits, these data suggest that daily dosing may be critical to allow for development of robust gamma oscillations.
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.|Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil.
authors.forename: Lezio S
authors.initials: LS
authors.lastname: Bueno-Junior
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Nicholas W
authors.initials: NW
authors.lastname: Simon
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Meredyth A
authors.initials: MA
authors.lastname: Wegener
authors.affiliation: Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Bita
authors.initials: B
authors.lastname: Moghaddam
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001611:Beta Rhythm / Q000187:drug effects; D065818:Gamma Rhythm / Q000187:drug effects*; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D013826:Theta Rhythm / Q000187:drug effects
chemical_list: D009538:Nicotine