Acute vagus nerve stimulation enhances reversal learning in rats

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

doi:10.1016/j.nlm.2021.107498

Cited by 14 publications

(13 citation statements)

References 142 publications

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“…Here we demonstrated that delivering VNS during, but not between CS presentations facilitated fear extinction, suggesting that temporal association between the memory reactivation and VNS is necessary for the enhancing effects of VNS. The observation that VNS must be delivered during fear cue presentation to be effective is consistent with previous studies in rodents showing that VNS paired with learning events facilitates the extinction of drug-seeking behavior and reversal learning 49 , 62 . These findings are in line with preclinical studies showing that VNS promotes neuronal plasticity and facilitates rehabilitation when delivered simultaneously with rehabilitation events 46 – 48 , 63 .…”

Section: Discussionsupporting

confidence: 89%

“…Importantly, studies indicate that choosing adequate stimulation parameters, including duration and intensity of stimulation, is critical in maximizing recovery after VNS-paired extinction 38 , 39 . In the same way that electrical stimulation parameters determine VNS efficacy 28 , 40 – 45 , the timing of VNS with respect to the concordant training regimens also critically determines efficacy 46 – 49 . Thus, the timing of VNS has the potential to influence its benefit to exposure-based therapy.…”

Section: Introductionmentioning

confidence: 99%

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Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD

Souza

Powers

Rennaker

et al. 2022

Sci Rep

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Studies have indicated that vagus nerve stimulation (VNS) enhances extinction learning in rodent models. Here, we investigated if pairing VNS with the conditioned stimulus is required for the enhancing effects of VNS. Adult Sprague–Dawley rats were exposed to intense stress followed by fear conditioning training to produce resistant fear. Rats were then implanted with a cuff electrode around the left vagus. After recovery, rats underwent extinction training paired with VNS (0.5 s, 0.8 mA, 100 µs, and 30 Hz) or with Sham VNS (0 mA). VNS rats were randomized into the following subgroups: During VNS (delivered during presentations of the conditioned stimulus, CS), Between VNS (delivered between CS presentations), Continuous VNS (delivered during the entire extinction session), and Dispersed VNS (delivered at longer inter-stimulation intervals across the extinction session). Sham VNS rats failed to extinguish the conditioned fear response over 5 days of repeated exposure to the CS. Rats that received Between or Dispersed VNS showed modest improvement in conditioned fear at the retention test. During and Continuous VNS groups displayed the greatest reduction in conditioned fear. These findings indicate that delivering VNS paired precisely with CS presentations or continuously throughout extinction promotes the maximum enhancement in extinction learning.

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Section: Discussionsupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD

Souza

Powers

Rennaker

et al. 2022

Sci Rep

View full text Add to dashboard Cite

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“…These effects were independent of potential VNS-induced reductions in anxiety, as acute VNS did not significantly affect exploratory behavior in an elevated plus maze. Our findings add to a growing body of literature that shows that even relatively brief VNS can affect cognitive functions [ 20 , 21 , 22 , 26 , 27 , 28 ]. In addition, our work identifies tasks covering multiple cognitive domains, that can be learned by rats in one or few sessions, and which are modulated by VNS, thus facilitating future studies into the effects of VNS on cognition.…”

Section: Introductionsupporting

confidence: 71%

“…Finally, VNS reduced the number of “never-reinforced” errors (responses that are incorrect during both the initial discrimination training and during the shift), which indicates that VNS-treated rats were more efficient in parsing out ineffective strategies [ 48 ]. The idea that VNS can enhance cognitive flexibility is also supported by a recent study that looked at the effects of VNS on reversal learning in rats [ 28 ].…”

Section: Discussionmentioning

confidence: 92%

Acute Vagus Nerve Stimulation Facilitates Short Term Memory and Cognitive Flexibility in Rats

et al. 2022

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Vagus nerve stimulation (VNS) causes the release of several neuromodulators, leading to cortical activation and deactivation. The resulting preparatory cortical plasticity can be used to increase learning and memory in both rats and humans. The effects of VNS on cognition have mostly been studied either in animal models of different pathologies, and/or after extended VNS. Considerably less is known about the effects of acute VNS. Here, we examined the effects of acute VNS on short-term memory and cognitive flexibility in naïve rats, using three cognitive tasks that require comparatively brief (single session) training periods. In all tasks, VNS was delivered immediately before or during the testing phase. We used a rule-shifting task to test cognitive flexibility, a novel object recognition task to measure short-term object memory, and a delayed spontaneous alternation task to measure spatial short-term memory. We also analyzed exploratory behavior in an elevated plus maze to determine the effects of acute VNS on anxiety. Our results indicate that acute VNS can improve memory and cognitive flexibility relative to Sham-stimulation, and these effects are independent of unspecific VNS-induced changes in locomotion or anxiety.

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“…This mechanism of action can be strengthened over multiple sessions of pairing to produce long-term permanent reorganization of sensory pathways that alters perception. Taken together, these works suggest phasic VNS has great potential as a next generation neuromodulation technology for rehabilitative motor and sensory therapies ( Neuhaus et al, 2007 ; Kreuzer et al, 2014 ; Engineer et al, 2015 ; Tyler et al, 2017 ; Vanneste et al, 2017 ; Kilgard et al, 2018 ; Adcock et al, 2020 ; Llanos et al, 2020 ; Thakkar et al, 2020 ; Altidor et al, 2021 ; Phillips et al, 2021 ).…”

Section: Lasting Alterations To Sensory Processing Occur Over Time Wh...mentioning

confidence: 86%

Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

2022

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After sensory information is encoded into neural signals at the periphery, it is processed through multiple brain regions before perception occurs (i.e., sensory processing). Recent work has begun to tease apart how neuromodulatory systems influence sensory processing. Vagus nerve stimulation (VNS) is well-known as an effective and safe method of activating neuromodulatory systems. There is a growing body of studies confirming VNS has immediate effects on sensory processing across multiple sensory modalities. These immediate effects of VNS on sensory processing are distinct from the more well-documented method of inducing lasting neuroplastic changes to the sensory pathways through repeatedly delivering a brief VNS burst paired with a sensory stimulus. Immediate effects occur upon VNS onset, often disappear upon VNS offset, and the modulation is present for all sensory stimuli. Conversely, the neuroplastic effect of pairing sub-second bursts of VNS with a sensory stimulus alters sensory processing only after multiple pairing sessions, this alteration remains after cessation of pairing sessions, and the alteration selectively affects the response properties of neurons encoding the specific paired sensory stimulus. Here, we call attention to the immediate effects VNS has on sensory processing. This review discusses existing studies on this topic, provides an overview of the underlying neuromodulatory systems that likely play a role, and briefly explores the potential translational applications of using VNS to rapidly regulate sensory processing.

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Acute vagus nerve stimulation enhances reversal learning in rats

Cited by 14 publications

References 142 publications

Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD

Timing of vagus nerve stimulation during fear extinction determines efficacy in a rat model of PTSD

Acute Vagus Nerve Stimulation Facilitates Short Term Memory and Cognitive Flexibility in Rats

Rapid Effects of Vagus Nerve Stimulation on Sensory Processing Through Activation of Neuromodulatory Systems

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