Post-training Unilateral Vagal Stimulation Enhances Retention Performance in the Rat

doi:10.1006/nlme.1995.1024

Neurobiology of Learning and Memory

Volume 63, Issue 3, May 1995, Pages 213-216

https://doi.org/10.1006/nlme.1995.1024 Get rights and content

Abstract

Many peripherally administered substances which modulate memory do not freely enter the brain. Such compounds may act through peripheral receptors that send messages centrally through vagal afferents. To explore this hypothesis, rats were chronically implanted with cuff electrodes on the left cervical vagus nerve. Each animal was trained 48 h after surgery on a one-trial inhibitory-avoidance task with a 0.75-mA, 1.0-s footshock. Immediately following training, each animal received either no stimulation or vagal stimulation (0.5-ms biphasic pulses; 20 Hz, 30 s) at one of three intensities (0.2, 0.4, 0.8 mA; eight animals per group). Retention was tested 24 h later. Neither the 0.2-in or 0.8-mA groups (22.1-s; 53.7-s median latency) showed altered retention performances, whereas the 0.4-mA group showed significantly improved retention (881.0 s) compared to unstimulated controls (21.1 s; U = 6, p < .01). This inverted-U shaped function indicates that vagal activation during memory consolidation modulates retention for memory tasks.

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Citation Excerpt :
Only the left branch of the vagus nerve was stimulated because the right branch of the VN innervates the sinoatrial node and stimulation of the right branch of the VN could lead to cardiac complications [19]. Considering that left cervical VNS is already FDA approved for neurological conditions and stimulation of the left VN has previously been found to improve cognitive performance in humans and rats, this study proceeded with left cervical VNS [5,8,19]. While freely moving in an arena (40 cm × 44 cm x 37 cm), rats were administered fifteen 100 μs biphasic pulse trains at 30 Hz, 0.8 mA constant current every 18 s for 30 min using an A365 Isostimulator (WPI).
Vagus nerve stimulation (VNS) improves cognition in humans and rodents, but the effects of a single session of VNS on performance and plasticity are not well understood.
Behavioral performance and hippocampal (HC) electrophysiology/neurotrophin expression were measured in healthy adult rats after VNS paired training to investigate changes in cognition and synaptic plasticity.
Platinum/iridium electrodes were surgically implanted around the left cervical branch of the VN of anesthetized male Sprague-Dawley rats (N = 47). VNS (100 μs biphasic pulses, 30 Hz, 0.8 mA) paired Novel Object Recognition (NOR)/Passive Avoidance Task (PAT) were assessed 24 h after training and post-mortem tissue was collected 48 h after VNS (N = 28). Electrophysiology recordings were collected using a microelectrode array system to assess functional effects on HC slices 90 min after VNS (N = 19). Sham received the same treatment without VNS and experimenters were blinded.
Stimulated rats exhibited improved performance in NOR (p < 0.05, n = 12) and PAT (p < 0.05, n = 14). VNS enhanced long-term potentiation (p < 0.05, n = 7–12), and spontaneous spike amplitude (p < 0.05, n = 7–12) and frequency (p < 0.05, n = 7–12) in the CA1. Immunohistochemical analysis found increased brain-derived neurotrophic factor expression in the CA1 (p < 0.05, n = 8–9) and CA2 (p < 0.01, n = 7–8).
These findings suggest that our VNS parameters promote synaptic plasticity and target the CA1, which may mediate the positive cognitive effects of VNS. This study significantly contributes to a better understanding of VNS mediated HC synaptic plasticity, which may improve clinical utilization of VNS for cognitive enhancement.

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Rapid CommunicationPost-training Unilateral Vagal Stimulation Enhances Retention Performance in the Rat

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Post-training Unilateral Vagal Stimulation Enhances Retention Performance in the Rat