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.
Subject(s)
Reversal Learning , Vagus Nerve Stimulation , 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/physiologyABSTRACT
Intracortical microelectrode arrays (MEAs) are valuable tools for neuroscience research, and their potential clinical use has been demonstrated. However, their inability to function reliably over chronic time points has limited their clinical translation. MEA failure is highly correlated with foreign body response (FBR), and therapeutics have been used to reduce FBR and improve device function, with drugs such as minocycline showing promising results in vivo. To avoid issues associated with systemic drug delivery, device coatings can be used to for therapeutic delivery. One method to locally deliver minocycline is a layer-by-layer (LBL) coating that consists of multiple trilayers of gelatin type A, minocycline, and dextran sulfate; however, the coating's impact on device function was previously unknown. This work characterized 10, 20, and 30 trilayer coatings and then evaluated their effect on device function. Cumulative minocycline release and coating thickness increased with the number of trilayers, agreeing with observations in previous studies. Atomic force microscopy images were used to calculate surface roughness of the coatings, which significantly increased from 10 to 20 trilayers and then remained relatively constant upon increasing to 30 trilayers. Scanning electron microscopy images confirmed that trilayers coated the MEAs. Electrochemical impedance spectroscopy (EIS) and charge carrying capacity (CCC) were used to evaluate the coating's effect on MEA electrochemical behavior over 3 weeks while the coated MEAs soaked in PBS. The 10 trilayer coatings slightly decreased CCC, while 20 and 30 trilayers initially increased CCC. CCC of all trilayers gradually increased as the MEAs soaked in PBS. All trilayers initially increased MEA impedance magnitude and reduced the phase angle at low frequencies. Impedance magnitude at 1 kHz and 15 kHz decreased toward their initial precoated values for all trilayers as the MEAs soaked in PBS. Overall, these results show that the LBL coatings did not significantly impact MEA function.
