Characterization of oscillatory changes in hippocampus and amygdala after deep brain stimulation of the infralimbic prefrontal cortex
Deep brain stimulation (DBS) is a new investigational therapy that has generated positive results in refractory depression. Although the neurochemical and behavioral effects of DBS have been examined, less attention has been paid to the influence of DBS on the network dynamics between different brain areas, which could contribute to its therapeutic effects. Herein, we set out to identify the effects of 1 h DBS in the infralimbic cortex (IL) on the oscillatory network dynamics between hippocampus and basolateral amygdala (BLA), two regions implicated in depression and its treatment. Urethane-anesthetized rats with bilaterally implanted electrodes in the IL were exposed to 1 h constant stimul…
Brain Activity Characterization Induced by Alcoholic Addiction: Spectral and Causality Analysis of Brain Areas Related to Control and Reinforcement of Impulsivity
Addiction to drugs generates modifications in the brain structure and its functions. In this work, an experimental model is described, using rats to characterize the brain activity induced by alcohol addiction. Four records were obtained using electrodes located in brain areas related to impulsivity control and reinforcement, i.e. the prelimbic (PL) and infralimbic (IL) cortex, together with the hippocampus (HPC). In the records, three main events related to the drinking action were selected: in the previous minute (T1), the first minute while drinking (T2) and the first minute after stopping drinking (T3).
Oral Monosodium Glutamate Administration Causes Early Onset of Alzheimer's Disease-Like Pathophysiology in APP/PS1 Mice.
Glutamate excitotoxicity has long been related to Alzheimer's disease (AD) pathophysiology, and it has been shown to affect the major AD-related hallmarks, amyloid-β peptide (Aβ) accumulation and tau phosphorylation (p-tau). We investigated whether oral administration of monosodium glutamate (MSG) has effects in a murine model of AD, the double transgenic mice APP/PS1. We found that AD pathogenic factors appear earlier in APP/PS1 when supplemented with MSG, while wildtype mice were essentially not affected. Aβ and p-tau levels were increased in the hippocampus in young APP/PS1 animals upon MSG administration. This was correlated with increased Cdk5-p25 levels. Furthermore, in these mice, we…
Neural oscillations in the infralimbic cortex after electrical stimulation of the amygdala. Relevance to acute stress processing
The stress system coordinates the adaptive reactions of the organism to stressors. Therefore, dysfunctions in this circuit may correlate to anxiety-related disorders, including depression. Comprehending the dynamics of this network may lead to a better understanding of the mechanisms that underlie these diseases. The central nucleus of the amygdala (CeA) activates the hypothalamic–pituitary–adrenal axis and brainstem nodes by triggering endocrine, autonomic and behavioral stress responses. The medial prefrontal cortex plays a significant role in regulating reactions to stressors, and is specifically important for limiting fear responses. Brain oscillations reflect neural systems activity. S…
The oscillatory profile induced by the anxiogenic drug fg-7142 in the amygdala-hippocampal network is reversed by infralimbic deep brain stimulation: Relevance for mood disorders
Anxiety and depression exhibit high comorbidity and share the alteration of the amygdala-hippocampal-prefrontal network, playing different roles in the ventral and dorsal hippocampi. Deep brain stimulation of the infralimbic cortex in rodents or the human equivalent-the subgenual cingulate cortex-constitutes a fast antidepressant treatment. The aim of this work was: (1) to describe the oscillatory profile in a rodent model of anxiety, and (2) to deepen the therapeutic basis of infralimbic deep brain stimulation in mood disorders. First, the anxiogenic drug FG-7142 was administered to anaesthetized rats to characterize neural oscillations within the amygdala and the dorsoventral axis of the …
Causal relationships between neurons of the nucleus incertus and the hippocampal theta activity in the rat
In recent years, a body of evidence has shown that the nucleus incertus (NI), in the dorsal tegmental pons, is a key node of the brainstem circuitry involved in hippocampal theta rhythmicity. Ascending reticular brainstem system activation evokes hippocampal theta rhythm with coupled neuronal activity in the NI. In a recent paper, we showed three populations of neurons in the NI with differential firings during hippocampal theta activation. The objective of this work is to better evaluate the causal relationship between the activity of NI neurons and the hippocampus during theta activation in order to further understand the role of the NI in the theta network. A Granger causality analysis w…
The effect of long context exposure on cued conditioning and c-fos expression in the rat forebrain
The c-fos expression was used to study the neural substrates of the cued fear conditioning acquisition, preceded by a short exposure versus a long exposure to the conditioning context. A long-context exposure (either during the night or during the day) prior to conditioning, was associated with low freezing in the learning test. Differences in the c-fos expression of CA1, CA3, BL Amygdala, LS and BNST were found between the short- or long-context groups with a pre-exposure before cued conditioning. Ce Amygdala showed no differences in the c-fos expression labeling. We reported the hippocampal c-fos activation during the cued fear conditioning acquisition. Specifically, the CA1 activation co…
Effects of Acute Stress on the Oscillatory Activity of the Hippocampus–Amygdala–Prefrontal Cortex Network
Displaying a stress response to threatening stimuli is essential for survival. These reactions must be adjusted to be adaptive. Otherwise, even mental illnesses may develop. Describing the physiological stress response may contribute to distinguishing the abnormal responses that accompany the pathology, which may help to improve the development of both diagnoses and treatments. Recent advances have elucidated many of the processes and structures involved in stress response management; however, there is still much to unravel regarding this phenomenon. The main aim of the present research is to characterize the response of three brain areas deeply involved in the stress response (i.e., to an …
Synchronized Activity in The Main and Accessory Olfactory Bulbs and Vomeronasal Amygdala Elicited by Chemical Signals in Freely Behaving Mice
AbstractChemosensory processing in mammals involves the olfactory and vomeronasal systems, but how the activity of both circuits is integrated is unknown. In our study, we recorded the electrophysiological activity in the olfactory bulbs and the vomeronasal amygdala in freely behaving mice exploring a battery of neutral and conspecific stimuli. The exploration of stimuli, including a neutral stimulus, induced synchronic activity in the olfactory bulbs characterized by a dominant theta rhythmicity, with specific theta-gamma coupling, distinguishing between vomeronasal and olfactory structures. The correlated activation of the bulbs suggests a coupling between the stimuli internalization in t…
Hyperammonemia alters the mismatch negativity in the auditory evoked potential by altering functional connectivity and neurotransmission
Minimal hepatic encephalopathy (MHE) is a neuropsychiatric syndrome produced by central nervous system dysfunction subsequent to liver disease. Hyperammonemia and inflammation act synergistically to alter neurotransmission, leading to the cognitive and motor alterations in MHE, which are reproduced in rat models of chronic hyperammonemia. Patients with MHE show altered functional connectivity in different neural networks and a reduced response in the cognitive potential mismatch negativity (MMN), which correlates with attention deficits. The mechanisms by which MMN is altered in MHE remain unknown. The objectives of this work are as follows: To assess if rats with chronic hyperammonemia rep…
Phencyclidine inhibits the activity of thalamic reticular gamma-aminobutyric acidergic neurons in rat brain.
Póster presentado en el IX Simposi de Neurobiologia Experimental, celebrado los días 22 y 23 de octubre de 2014 en Barcelona y organizado por la Societat Catalana de Biologia del Institut d'Estudis Catalans
Subchronic vortioxetine treatment -but not escitalopram- enhances pyramidal neuron activity in the rat prefrontal cortex.
Abstract Vortioxetine (VOR) is a multimodal antidepressant drug. VOR is a 5-HT 3 -R, 5-HT 7 -R and 5-HT 1D -R antagonist, 5-HT 1B -R partial agonist, 5-HT 1A -R agonist, and serotonin transporter (SERT) inhibitor. VOR shows pro-cognitive activity in animal models and beneficial effects on cognitive dysfunction in major depressive patients. Here we compared the effects of 14-day treatments with VOR and escitalopram (ESC, selective serotonin reuptake inhibitor) on neuronal activity in the medial prefrontal cortex (mPFC). Ten groups of rats (5 standard, 5 depleted of 5-HT with p -chlorophenylalanine -pCPA-, used as model of cognitive impairment) were fed with control food or with two doses of …
Depressive-like symptoms in a reserpine-induced model of fibromyalgia in rats.
Since the pathogenesis of fibromyalgia is unknown, treatment options are limited, ineffective and in fact based on symptom relief. A recently proposed rat model of fibromyalgia is based on central depletion of monamines caused by reserpine administration. This model showed widespread musculoskeletal pain and depressive-like symptoms, but the methodology used to measure such symptoms has been criticized. Evidence relates the high prevalence of pain and depression in fibromyalgia to common pathogenic pathways, most probably focused on the monoaminergic system. The present study aims at a validation of the reserpine model of fibromyalgia. For this purpose, rats undergoing this model have been …
Regular theta-firing neurons in the nucleus incertus during sustained hippocampal activation
This paper describes the existence of theta-coupled neuronal activity in the nucleus incertus (NI). Theta rhythm is relevant for cognitive processes such as spatial navigation and memory processing, and can be recorded in a number of structures related to the hippocampal activation including the NI. Strong evidence supports the role of this tegmental nucleus in neural circuits integrating behavioural activation with the hippocampal theta rhythm. Theta oscillations have been recorded in the local field potential of the NI, highly coupled to the hippocampal waves, although no rhythmical activity has been reported in neurons of this nucleus. The present work analyses the neuronal activity in t…
Aβ Induces Excitotoxicity Mediated by APC/C-Cdh1 Depletion That Can Be Prevented by Glutaminase Inhibition Promoting Neuronal Survival
AbstractThe E3 ubiquitin ligase anaphase-promoting complex/cyclosome (APC/C) is activated by the fizzy-related protein homolog/CDC20-like protein 1 (cdh1) in post-mitotic neurons. Growing evidence suggests that dysregulation of APC/C-Cdh1 is involved in neurodegenerative diseases. Here we show in neurons that oligomers of amyloid beta (Aβ), a peptide related to Alzheimer’s disease, cause proteasome-dependent degradation of cdh1. This leads to a subsequent increase in glutaminase (a degradation target of APC/C-Cdh1), which causes an elevation of glutamate levels and further intraneuronal Ca2+ dysregulation, resulting in neuronal apoptosis. Glutaminase inhibition prevents glutamate excitotoxi…
Hippocampal oscillatory dynamics and sleep atonia are altered in an animal model of fibromyalgia: Implications in the search for biomarkers
The pathogenesis of fibromyalgia is still unknown. Core symptoms include pain, depression, and sleep disturbances with high comorbidity, suggesting alterations in the monoaminergic system as a common origin of this disease. The reserpine-induced myalgia (RIM) model lowers pain thresholds and produces depressive-like symptoms. The present work aims to evaluate temporal dynamics in the oscillatory profiles and motor activity during sleep in this model and to evaluate if the model mimics the sleep disorders that occur in fibromyalgia patients. Hippocampal and electromyogram activity were recorded in chronically implanted rats. Following 3 days of basal recordings, reserpine was administered on…
A standardization of the Novelty-Suppressed Feeding Test protocol in rats
Tests based on hyponeophagia phenomena are the most widely used to check the efficacy and efficiency of new-generation chronic antidepressant treatments. Even so, these tests lack strict consensus about their methodology, which reduces their validity, reproducibility and makes translatability difficult. Therefore, after an extensive literature review on this subject, we propose a methodological protocol for the Novelty-Suppressed Feeding Test to normalize this situation. Animals were induced to a reserpine-induced depression model and were then chronically treated with duloxetine, desvenlafaxine or vehicle. After a 14-day treatment, a standardized Novelty-Suppressed Feeding Test was perform…
Perineuronal Nets Regulate the Inhibitory Perisomatic Input onto Parvalbumin Interneurons and γ Activity in the Prefrontal Cortex
Parvalbumin-expressing (PV+) interneurons play a key role in the maturation and synchronization of cortical circuitry and alterations in these inhibitory neurons, especially in the medial prefrontal cortex (mPFC), have been found in different psychiatric disorders. The formation of perineuronal nets (PNNs) around many of these interneurons at the end of the critical periods reduces their plasticity and sets their connectivity. Consequently, the presence of PNNs must have an important impact on the synaptic input and the physiology of PV+ cells. In the present study, we have found that in adult male mice, prefrontocortical PV+ cells surrounded by PNNs show higher density of perisomatic excit…
Real-Time Localization of Epileptogenic Foci EEG Signals: An FPGA-Based Implementation
The epileptogenic focus is a brain area that may be surgically removed to control of epileptic seizures. Locating it is an essential and crucial step prior to the surgical treatment. However, given the difficulty of determining the localization of this brain region responsible of the initial seizure discharge, many works have proposed machine learning methods for the automatic classification of focal and non-focal electroencephalographic (EEG) signals. These works use automatic classification as an analysis tool for helping neurosurgeons to identify focal areas off-line, out of surgery, during the processing of the huge amount of information collected during several days of patient monitori…
Induced Dipoles and Possible Modulation of Wireless Effects in Implanted Electrodes. Effects of Implanting Insulated Electrodes on an Animal Test to Screen Antidepressant Activity
There is evidence that Deep Brain Stimulation (DBS) produces health benefits in patients even before initiating stimulation. Furthermore, DBS electrode insertion in rat infralimbic cortex (ILC) provokes antidepressant-like effects before stimulation, due to local inflammation and astrogliosis. Consequently, a significant effect of implanting electrodes is suspected. External fields, similar in magnitude to the brain’s endogenous fields, induce electric dipoles in conducting materials, in turn influencing neural cell growth through wireless effects. To elucidate if such dipoles influence depressive-like behavior, without external stimulation, the comparative effect of conducting and insulate…
Glutamatergic projection from the nucleus incertus to the septohippocampal system
Abstract Recent findings support a relevant role of the nucleus incertus in the control of the hippocampal activity through the modulation of theta rhythm. Previous studies from our group have shown that this nucleus is a critical relay between reticularis pontis oralis and the medial septum/diagonal band, regarded as the main activator and the pacemaker of the hippocampal oscillations, respectively. Besides, the nucleus incertus is highly linked to activated states related to the arousal response. The neurotransmission of the nucleus incertus, however, remains uncertain. Only GABA and the neuromodulator relaxin 3 are usually considered to be involved in its contribution to the septohippoca…
Anatomical evidence for a ponto-septal pathway via the nucleus incertus in the rat.
Abstract Hippocampal theta activity is involved in sensory–motor integration and constitutes a functional basis for mnemonic functions. The medial septum–diagonal band of Broca (MS/DBv) is a key structure as pacemaker of the oscillation. In addition, some brainstem reticular structures are crucial for the activation of MS/DBv. Specifically, the nucleus reticularis pontis oralis (RPO) is considered the most effective pontine site for eliciting theta rhythm. Nevertheless, its connection with the MS/DBv is not direct. A previous study by our group pointed out that the nucleus incertus (NI) could be considered as a relay in this multisynaptic pathway. From this study, the stimulation of RPO inc…