Alejandro Valdés-Cruz

Vagus nerve prolonged stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes.

Summary: Purpose: To analyze the effect of prolonged (daily) electrical vagus nerve stimulation (VNS) on daily amygdaloid kindling (AK) in freely moving cats.

Effect of electrical stimulation of the nucleus of the solitary tract on the development of electrical amygdaloid kindling in the cat.

Summary:  Purpose: This work analyzed the effect of electrical stimulation of the nucleus of the solitary tract (NTS) on the development of electrical amygdaloid kindling (AK) in freely moving cats.

Chronic stimulation of the cat vagus nerve Effect on sleep and behavior

The effect of electrical vagus nerve stimulation (VNS) on sleep and behavior was analyzed in freely moving cats. Eight cats were prepared for 23-h sleep recordings. The left vagus nerve of four of them was stimulated during 1 min, five times at 1-h intervals, for 5 days. The VNS induces: ipsilateral myosis, blinking, licking, abdominal contractions, upward gaze, swallowing, and eventually yawning and compulsive eating, as well as an increase of ponto-geniculate-occipital (PGO) wave density and of the number of stages and total amount of rapid eye movement (REM) sleep. Besides, there was a sudden transition from waking stage to REM sleep. The present results suggest that VNS modifies sleep in the cat. This effect could be explained by an activation of the areas involved in the physiological mechanisms of sleep.

Preemptive effect of nucleus of the solitary tract stimulation on amygdaloid kindling in freely moving cats

Purpose:  The nucleus of the solitary tract (NTS) is a primary site where vagal afferents terminate. The aim of this study was to analyze the preemptive effect of NTS electrical stimulation on daily amygdaloid kindling (AK) in freely moving cats.

Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats

A neonatal ventral hippocampal lesion (NVHL) in rats has been commonly used as a neurodevelopmental model to mimic schizophrenia‐like behaviors. Recently, we reported that NVHL resulted in dendritic retraction and spine loss in pyramidal neurons of the prefrontal cortex (PFC). In addition, the hippocampus and PFC are important structures in the regulation of the electroencephalographic (EEG) activity. Patients with PFC lesions show deficits in the EEG activity. This study aimed to determine whether the EEG activity was altered in NVHL rats. In addition, we also analyzed the locomotor activity induced by a novel environment and exploratory behavior using the hole‐board test. Consistent with the behavioral findings, the EEG analysis of the cortical regions showed that the NVHL rats displayed a lower power in cortical bands. At 1–8 Hz, 9–14 Hz, and 15–30 Hz bands, our findings showed a decrease in the absolute power of the parietal and occipital cortices recordings. In addition, the NVHL rats also showed a reduction in the exploratory behavior tested using the hole‐board test. In conclusion, this study demonstrated that the EEG activity was reduced in adult NVHL rats and suggests that this may play a role in the behavioral changes observed in this neurodevelopmental model of schizophrenia. Synapse, 2012.

Long-term changes in sleep and electroencephalographic activity by chronic vagus nerve stimulation in cats.

We previously reported the effect of vagus nerve electrical stimulation (VNS) on sleep and behavior in cats. The aim of the present study is to analyze the long-term effects of VNS on the electroencephalographic (EEG) power spectrum and on the different stages of the sleep-wakefulness cycle in the freely moving cat. To achieve this, six male cats were implanted with electrodes on the left vagal nerve and submitted to 15 rounds of 23 h continuous sleep recordings in three categories: baseline (BL), VNS and post-stimulus recording (PSR). The following parameters were analyzed: EEG power spectrum, total time and number of sleep phases, ponto-geniculo-occipital (PGO) wave density of the rapid eye movement (REM) sleep, and the number of times the narcoleptic reflex was present (sudden transition from wakefulness to REM sleep). Significant changes were detected, such as an enhancement of slow-wave sleep (SWS) stage II; a power increase in the bands corresponding to sleep spindles (8-14 Hz) and delta waves (1-4 Hz) with VNS and PSR; an increase in the total time, number of stages, and density of PGO wave in REM sleep with VNS; a decrease of wakefulness in PSR, and the eventual appearance of the narcoleptic reflex with VNS. The results show that the effect of the VNS changes during different stages of the sleep-wakefulness cycle. In REM sleep, the effect was present only during VNS, while the SWS II was affected beyond VNS periods. This suggests that ponto-medullar and thalamic mechanisms of slow EEG activity may be due to plastic changes elicited by vagal stimulation.

Effects of electrical stimulation of the vagus nerve on the development of visual habituation in the cat

The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.

Short-term deep brain stimulation of the thalamic reticular nucleus modifies aberrant oscillatory activity in a neurodevelopment model of schizophrenia

Dysfunction of thalamo-cortical networks involving particularly the thalamic reticular nucleus (TRN) is implicated in schizophrenia. In the neonatal ventral hippocampal lesion (NVHL), a heuristic animal model of schizophrenia, brain oscillation changes similar to those of schizophrenic patients have been reported. The aim of this study was to analyze the effects of short-term deep brain stimulation (DBS) in the thalamic reticular nucleus on electroencephalographic (EEG) activity in the NVHL. Male and female Sprague-Dawley rats were used and the model was prepared by excitotoxicity damage of the ventral hippocampus on postnatal day 7 (PD-7). Chronic bilateral stainless steel electrodes were implanted in the TRN, thalamic dorsomedial nucleus and prelimbic area at PD-90. Rats were classified as follows: sham and NVHL groups, both groups received bilateral DBS in the TRN for one hour (100Hz, 100µs pulses, 200µA). All animals showed a sudden behavioral arrest accompanied by widespread symmetric bilateral spike-wave discharges, this activity was affected by DBS-TRN. Additionally, the power spectra of 0.5-100Hz and the coherence of 0.5-4.5 and 35-55Hz frequencies were modified by DBS-TRN. Our results suggest that DBS in the TRN may modify functional connectivity between different parts of the thalamo-cortical network. Additionally, our findings may suggest a beneficial effect of DBS-TRN on some preclinical aberrant oscillatory activities in a neurodevelopmental model of schizophrenia.

Vagus Nerve Stimulation

Vagal stimulation inhibits brainstem neuronal discharge and induces slow wave sleep (SWS) and rapid eye movements (REM) sleep in the cat3,2,8. It also inhibits motor activity10. Low-voltage vagal stimulation also significantly reduces EEG spiking activity of a cortical epileptic focus caused by topical application of strychnine12 and prevents or aborts electrically and chemically induced seizures in rats13 as well as PTZ induced seizures in dogs14. In a previous work4 we described signs of paradoxical (REM) sleep that appear during the extinction of experimental seizures, suggesting a close relationship between the appearance of REM sleep and seizure arrest. The vagal stimulation as a novel approach for seizure control in patients who have intractable epilepsy has been recently documented7,6. In the present study we assessed the efficacy of vagal nerve stimulation on the development of electrographic and behavioral changes induced by kindling the amygdala (KA) as measured by the reduction in the frequency, duration and cortical propagation of amygdaloid afterdischarge.

Sleep in the Work of Marcos José Salgado, Author of the First Book of Physiology in the Americas, Published in 1727

Sleep and wakefulness are functions of the central nervous system (CNS) that are altered in numerous psychiatric disorders. Interestingly, Marcos Jose Salgado published in 1727 his book which is considered the first book of Physiology in the American continent and entitled “Cursus Medicus Mexicanus” (Figure 1) that suggests the use of drugs to regulate brain functions and their therapeutic action on sleep. In the work of Salgado, the concepts of sleep and wakefulness are offered using Hippocratic and Galenic knowledge to explain the pathophysiology of both functions. Today those concepts might be considered wrong. However, taking into account the historical moment and the intrinsic value of the text written in Latin, this manuscript is unique. Considered by art critics as valuable, there are only eight original copies of this book. In the present report, we discussed paragraph by paragraph the chapter “Sleep and wakefulness”, the work of this Medical Doctor of the New Spain.