Noradrenergic α1, α2, and ß1receptors mediate VNS-induced theta oscillations.

Although vagal nerve stimulation (VNS) has been employed with success for almost four decades in many central nervous system disturbances, the physiological and pharmacological processes underlying this therapy are still unclear. Searching for central mechanisms of VNS is clinically limited. Hence, in many experiments, VNS technique is tested on the model of laboratory animals. In the present study we proceed with the experiments to verify some central effects of VNS. Specifically, we focussed on the hippocampal formation (HPC) noradrenergic profile which underlines the VNS-induced theta oscillations in anesthetized rats (Broncel et al., 2017; 2021). The effects of noradrenaline (NE) and selective noradrenergic α and ß agonists and antagonists were tested in experiments organized in three stages. Initially, a nonspecific noradrenergic agonist, noradrenaline, was administrated. In the second stage, noradrenergic α and ß agonists were applied. In the last stage, the administration of selected agonists was pretreated by specific antagonists. The results of the present study provide evidence that the selective activation of HPC α1, α2, and ß1 noradrenergic receptors produce the inhibition of VNS-induced theta oscillations. Hippocampal ß2 and ß3 receptors were found not to be involved in the modulation of oscillations produced by the vagal nerve stimulation. The obtained outcomes are discussed in light of the effects of increased exogenous NE and induced release of endogenous NE.

Noradrenergic Profile of Hippocampal Formation Theta Rhythm in Anaesthetized Rats.

The present study was undertaken to identify the noradrenergic receptors underlying the production of hippocampal formation (HPC) type 2 theta rhythm. The experiments were performed on urethanized rats wherein type 2 theta is the only rhythm present. In three independent stages of experiments, the effects of noradrenaline (NE) and selective noradrenergic α and ß agonists and antagonists were tested. We indicate that the selective activation of three HPC noradrenergic receptors, α1, α2 and ß1, induced a similar effect (i.e., inhibition) on type 2 theta rhythm. The remaining HPC ß2 and ß3 noradrenergic receptors do not seem to be directly involved in the pharmacological mechanism responsible for the suppression of theta rhythm in anaesthetized rats. Obtained results provide evidence for the suppressant effect of exogenous NE on HPC type 2 theta rhythm and show the crucial role of α1, α2 and ß1 noradrenergic receptors in the modulation of HPC mechanisms of oscillations and synchrony. This finding is in contrast to the effects of endogenous NE produced by electrical stimulation of the locus coeruleus (LC) and procaine injection into the LC (Broncel et al., 2020).

Effects of locus coeruleus activation and inactivation on hippocampal formation theta rhythm in anesthetized rats.

Previously obtained data suggests that noradrenaline (NE) released from the efferent locus coeruleus (LC) endings in hippocampal formation (HPC) may serve as an important modulating signal involved in the pharmacological mechanisms responsible for the production of type 2 theta rhythm in rats. Hence, two distinct hypotheses were tested in the present study: 1/ if the decrease in HPC level of NE is correlated with the desynchronization of HPC field potential, then the inhibition of LC would be expected to abolish HPC type 2 theta rhythm; 2/ if the increase in HPC NE level is correlated with synchronization of HPC field potential, then the stimulation of LC would be expected to produce type 2 theta. The experiments were performed using an experimental model of HPC type 2 theta rhythm recorded in urethanized rats. It was demonstrated that electrical stimulation of LC produced type 2 theta rhythm whereas procaine injection into LC, in contrast, reversibly abolished type 2 theta. The possible relation of type 2 theta rhythm with some disturbances of Alzheimer disease are addressed.

Vagal nerve stimulation as a promising tool in the improvement of cognitive disorders.

Vagal nerve stimulation (VNS) is known as an effective method of treatment in a number of neurological disorders. The low risk of side effects also makes it useful in clinical trials in other diseases. Branches of the vagal nerve innervate the anatomical structures known to be involved in memory processing. That is why it seems justified that several studies emphasize the impact of VNS on the cognitive and memory function in both healthy volunteers and patients with epilepsy and Alzheimer's disease. Results have shown that VNS can modulate different types of memory depending the protocol of stimulation in non-demented patients after both short term and chronic VNS application. Transcutaneous vagal nerve stimulation (tVNS), which is a non-invasive method of VNS, opens up new perspectives for different clinical applications.

[Clinical applications of late negative evoked potentials--contingent negative variation (CNV)]. / Zastosowanie kliniczne póznego warunkowego potencjalu wywolanego--(PWPW)--contingent negative variation (CNV).

Contingent negative variation /CNV/ is a slow negative potential described first in 1964 by Walter et al. It is a correlate of cerebral activity in the frontal lobes connected with expectation of stimulus and frontal cortex preparation for the stimulus to come. CNV develops in the time between the warning signal /S1/ and the commanding signal /S2/. CNV contains two main components connected directly with brain function: the first one, so called early component, is connected with the process of orientation or warning /it is called also orientation wave/, the second one /late component/ is connected with the preparation for movement /expectation wave or preparatory wave/. The clinical application of CNV is for the evaluation of the correlation of potential changes with changes in cognitive functions occurring in various diseases. Numerous studies reported recently have confirmed the applicability of CNV on the diagnosis of dementia, Parkinson's disease, epilepsy, schizophrenia, anxiety states, chronic pains, including migraine.