Vagus nerve stimulation-induced cognitive enhancement: Hippocampal neuroplasticity in healthy male rats.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Polarity and subfield specific effects of transcranial direct current stimulation on hippocampal plasticity.

An increasing number of studies using human subjects substantiate the use of transcranial direct current stimulation (tDCS) as a noninvasive approach to treat various neurological symptoms. tDCS has been tested in conditions from motor to cognition dysfunctions. Performance enhancement of healthy subjects using tDCS has also been explored. The underlying physiological mechanism for tDCS effects is hypothesized to be through changes in neuroplasticity and we have previously demonstrated that in vivo anodal tDCS can enhance neuroplasticity of hippocampal CA1 neurons. The purpose of this study was to determine whether the underlying electrophysiological changes that occur following in vivo tDCS are polarity specific. We also examined both the CA1 and CA3 regions of the hippocampus to determine whether the tDCS effects were subfield specific. We conducted in vivo tests of cathodal tDCS versus anodal tDCS on synaptic plasticity of CA1 and CA3 neurons of male rats. In each region we assessed long term potentiation (LTP), paired pulse facilitation (PPF) and long term depression (LTD). In the CA1 region, we found anodal tDCS significantly enhanced not only LTP and PPF, but also LTD. There was no statistical difference in LTP, PPF or LTD of hippocampal CA1 neurons resulting from cathodal tDCS. Neither anodal nor cathodal tDCS induced significant changes in neuroplasticity of hippocampal CA3 neurons. Results indicate that the effects of tDCS are subfield specific and polarity dependent with anodal tDCS having greater impact on synaptic activity in the rat hippocampus than cathodal tDCS.