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.

The Role of Gamma Oscillations in the Pathophysiology of Substance Use Disorders

“…In the following experiment, a separate group of rats was treated with nicotine following the same daily dosing regimen. Nicotine-treated rats performed significantly better in a visual attention task compared to controls, verifying the cognitive enhancing effects of nicotine [ 60 ]. In sum, nicotine administration increases gamma band activity.…”

“…Recently, Bueno-Junior and colleagues examined the effects of acute versus chronic nicotine exposure on brain oscillatory activity in rats [ 60 ]. The authors implemented a daily dosing regimen of nicotine (0.2 mg/kg) in vivo and found that acute nicotine administration slightly increased gamma power and reduced theta and beta power.…”

“…The authors implemented a daily dosing regimen of nicotine (0.2 mg/kg) in vivo and found that acute nicotine administration slightly increased gamma power and reduced theta and beta power. Daily nicotine exposure produced stronger and more robust gamma activity [ 60 ]. In the following experiment, a separate group of rats was treated with nicotine following the same daily dosing regimen.…”

A Distinctive Pattern of Hippocampal-Prefrontal Cortical Network Activity during Stress Predicts Learned Resistance

“…Neurons were labeled as modulated or non-modulated based on stimulus reactivity through comparing pre-CS spike counts versus during-CS and post-US spike counts via one-tailed paired t-tests. Modulated neurons were then classified as excited (higher spike count) or suppressed (lower spike count) by each stimulus (CS or US) (Bueno-Junior et al, 2017Wood et al, 2012) (Figure 6B). The p-value of this categorization was Bonferroni corrected based on the total number of neurons from all groups (N = 110, p = 0.0004) ( Figure 6B).…”

Nicotine Enhances Firing Activity of Layer 5 Pyramidal Neurons in the Medial Prefrontal Cortex through Inhibition of Kv7 Channels

“…[12][13][14][15] Both α4β2 and α7 nAChRs are expressed in the mPFC in a layer-specific manner; in layers 2/3, nAChRs are mainly expressed in γ-aminobutyric acid (GABA)-ergic interneurons, whereas in the deeper layers 5/6, both glutamatergic pyramidal neurons and GABAergic interneurons, as well as glutamatergic presynaptic terminals, express the nAChRs. [16][17][18] It has been reported that nicotineinduced enhancements of attention, working memory and recognition are associated with long-lasting activities of mPFC neurons. [19][20][21][22] Considering that the nicotine-induced potentiation of excitatory transmission in mPFC pyramidal neurons readily disappears due to a desensitization of nAChRs, 17,23) it was hypothesized that there exit other mechanism(s) that generates a persistent increase in mPFC neuronal activity.…”