Deep Brain Stimulation (DBS) Applications

The issue is dedicated to applications of Deep Brain Stimulation and, in this issue, we would like to highlight the new developments that are taking place in the field. These include the application of new technology to existing indications, as well as ‘new’ indications. We would also like to highlight the most recent clinical evidence from international multicentre trials. The issue will include articles relating to movement disorders, pain, psychiatric indications, as well as emerging indications that are not yet accompanied by clinical evidence. We look forward to your expert contribution to this exciting issue

Transcranial magnetic stimulation of the brain: What is stimulated? – A consensus and critical position paper

Copyright © 2022 The Author(s) and International Federation of Clinical Neurophysiology. Transcranial (electro)magnetic stimulation (TMS) is currently the method of choice to non-invasively induce neural activity in the human brain. A single transcranial stimulus induces a time-varying electric field in the brain that may evoke action potentials in cortical neurons. The spatial relationship between the locally induced electric field and the stimulated neurons determines axonal depolarization. The induced electric field is influenced by the conductive properties of the tissue compartments and is strongest in the superficial parts of the targeted cortical gyri and underlying white matter. TMS likely targets axons of both excitatory and inhibitory neurons. The propensity of individual axons to fire an action potential in response to TMS depends on their geometry, myelination and spatial relation to the imposed electric field and the physiological state of the neuron. The latter is determined by its transsynaptic dendritic and somatic inputs, intrinsic membrane potential and firing rate. Modeling work suggests that the primary target of TMS is axonal terminals in the crown top and lip regions of cortical gyri. The induced electric field may additionally excite bends of myelinated axons in the juxtacortical white matter below the gyral crown. Neuronal excitation spreads ortho- and antidromically along the stimulated axons and causes secondary excitation of connected neuronal populations within local intracortical microcircuits in the target area. Axonal and transsynaptic spread of excitation also occurs along cortico-cortical and cortico-subcortical connections, impacting on neuronal activity in the targeted network. Both local and remote neural excitation depend critically on the functional state of the stimulated target area and network. TMS also causes substantial direct co-stimulation of the peripheral nervous system. Peripheral co-excitation propagates centrally in auditory and somatosensory networks, but also produces brain responses in other networks subserving multisensory integration, orienting or arousal. The complexity of the response to TMS warrants cautious interpretation of its physiological and behavioural consequences, and a deeper understanding of the mechanistic underpinnings of TMS will be critical for advancing it as a scientific and therapeutic tool.Aman S. Aberra was supported by a U. S. A. National Science Foundation Graduate Research Fellowship (No. DGF 1106401). Andrea Antal has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01GP2124B) and by a grant of the Lower Saxony Ministry of Science and Culture (Grant 76251-12-7/19 ZN 3456). Marco Davare has been supported by a BBSRC responsive mode grant. Klaus Funke has been supported by a grant of the Federal Ministry of Education and Research (BMBF) of Germany (Grant 01EE1403B) as part of the German Center for Brain Stimulation (GCBS) and by the Deutsche Forschungsgemeinschaft (DFG) (Grants FU256/3-2; 122679504–SFB874). Mark Hallett is supported by the NINDS Intramural Program. Anke N. Karabanov holds a 4-year Sapere Aude Fellowship which is sponsored by the Independent Research Fund Denmark (Grant Nr. 0169-00027B). The sponsor had no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Giacomo Koch has been supported by na EU grant H2020-EU.1.2.2. - FET Proactive (Neurotwin ID: 101017716). Sabine Meunier is Emeritus Research Director at INSERM, this has no direct involvement in the collection, analysis and interpretation of data and in the writing of the manuscript. Carlo Miniussi has been supported by a grant of the Caritro Foundation, Italy. Walter Paulus received grants from the Deutsche Forschungsgemeinschaft and BMBF. Angel V. Peterchev was supported by grants from the U. S. A. National Institutes of Health (Grants Nos. R01NS117405, R01NS088674, RF1MH114268, R01MH111865). Traian Popa has been supported by the Defitech Foundation and NIBS-iCog grant from the Swiss National Science Foundation. Hartwig R. Siebner holds a 5-year professorship in precision medicine at the Faculty of Health Sciences and Medicine, University of Copenhagen which is sponsored by the Lundbeck Foundation (Grant Nr. R186-2015-2138). The salary for Janine Kesselheim (PhD project) has been covered by a project grant “Biophysically adjusted state-informed cortex stimulation” (BASICS) funded by a synergy grant from Novo Nordisk Foundation (PI: Hartwig R Siebner, Interdisciplinary Synergy Program 2014; grant number NNF14OC001). Axel Thielscher has been supported by grants of the Lundbeck foundation (R118-A11308, R244-2017-196 and R313-2019-622). Yoshikazu Ugawa has been supported in part by grants from the Research Project Grant-in-aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology (Grants 15H05881, 16H05322, 19H01091, 20K07866). Ulf Ziemann received grants from the German Ministry of Education and Research (BMBF), European Research Council (ERC), and German Research Foundation (DFG)

Status Epilepticus Induced Alterations in Hippocampal Anatomy and Neurotransmission

Status epilepticus (SE) is a life-threatening neurologic emergency occurring when the brain is in an unrelenting state of seizure activity. Approximately 40% of people who encounter a single event of SE go on to develop epilepsy, characterized by spontaneously occurring seizures. While the exact mechanisms underlying seizure origin are not understood, at a fundamental level seizures initiate due to an imbalance between inhibitory and excitatory neurotransmission. We explored the impact of SE and the development of epilepsy on GABAA receptor mediated inhibitory neurotransmission and kainate receptor (KAR) mediated excitatory neurotransmission. Stiripentol (STP), a positive allosteric modulator of the GABAA receptor, was found to terminate both brief and prolonged SE with the development of less pharmacoresistance than is observed with the benzodiazepine (BZD), diazepam (DZP). In addition STP, but not DZP, retained its ability to potentiate both phasic and tonic GABAergic transmission post-SE. These findings are supported by previous studies demonstrating that the actions of STP do not require the BZD-sensitive γ2-containing GABAARs which are internalized during prolonged SE. These data demonstrate that prolonged SE significantly impacts the pharmacological profile of GABAA receptors and potential therapeutics. x KARs densely populate the hippocampal mossy fiber – CA3 pathway where they mediate a portion of excitatory neurotransmission. Significant alterations in KAR subunit expression in the dentate gyrus and CA3 regions were observed in animals at 5, 60 and 200 day post-SE. These changes were dynamic and region specific. In agreement with observed alterations in subunit expression, KAR-mediated neurotransmission was significantly reduced at mossy fiber – CA3 synapses in epileptic animals. In addition, synaptic integration by KARs during repetitive stimulation was also significantly impaired. These data demonstrate that SE significantly impacts KAR-mediated excitatory neurotransmission. Together these studies provide new insight into the impact of SE and the development of epilepsy on both GABAA and KAR-mediated neurotransmission. The observed alterations following SE may contribute to the generation of seizures or may be compensatory mechanisms to reduce the likelihood of seizure initiation. Furthermore, these findings demonstrate the dramatic alterations observed in the diseased brain and emphasize the importance of acknowledging these differences for the development of effective therapeutics

Diagnosis and Treatment of Parkinson's Disease

Parkinson's disease is diagnosed by history and physical examination and there are no laboratory investigations available to aid the diagnosis of Parkinson's disease. Confirmation of diagnosis of Parkinson's disease thus remains a difficulty. This book brings forth an update of most recent developments made in terms of biomarkers and various imaging techniques with potential use for diagnosing Parkinson's disease. A detailed discussion about the differential diagnosis of Parkinson's disease also follows as Parkinson's disease may be difficult to differentiate from other mimicking conditions at times. As Parkinson's disease affects many systems of human body, a multimodality treatment of this condition is necessary to improve the quality of life of patients. This book provides detailed information on the currently available variety of treatments for Parkinson's disease including pharmacotherapy, physical therapy and surgical treatments of Parkinson's disease. Postoperative care of patients of Parkinson's disease has also been discussed in an organized manner in this text. Clinicians dealing with day to day problems caused by Parkinson's disease as well as other healthcare workers can use beneficial treatment outlines provided in this book

Towards a Better Treatment of Parkinson\u27s disease

Current therapies for Parkinson\u27s Disease, the second most common neurodegenerative disorder, do not prevent disease progression, and induce extremely detrimental side-effects. Improving the best current pharmacological therapy, L-DOPA, carries important clinical benefits, partly by reducing the dose-related side-effects which occur after five to ten years of use. Thus the central aim of this proposal is to determine whether low doses of a D2 antagonist may, by selectively blocking the dopamine autoreceptor-mediated feedback inhibition of dopamine neurons, potentiate L-DOPA\u27s effect on individual basal ganglia neurons and its antiparkinsonian effects in Parkinsonian animals. Electrophysiology (extracellular single-cell recording in the globus pallidus) and behavioral (cylinder test) studies were performed to determine if co-administration of a small dose of the D2 antagonist raclopride with L-DOPA results in an enhanced therapeutic effect of L-DOPA in 6-OHDA lesioned (parkinsonian) rats. Preliminary data revealed different subgroups of pallidal neurons, with different responses to L-DOPA injection. However, we showed that a major method by which sub-groups of pallidal neurons have been identified in previous studies was unreliable, halting further study of L-DOPA\u27s effect on different subgroups of pallidal neurons using that method. Thus, we focused on classification of pallidal neurons and the changes of these neurons in Parkinsonian animals. Previous studies report pallidal neurons as Type-I (negative initial peak) or Type-II (initial positive peak). Our studies suggest electrode impedance determines whether the recorded waveform is Type-I (low impedance electrode) or Type-II (high impedance electrode). Pallidal neurons can be more reliably classified based on functional connectivity with cortical neurons. More importantly, our findings showed that, in Parkinsonian rats, pallidal neurons positively coupled to cortical activity usually lag, while in control rats close to half of pallidal neurons lead cortical activity. Also, we found significantly increased cortical control of pallidal neurons in Parkinsonian rats indicated by a significant increase in the observed number of pallidal cells negatively coupled to cortical activity. The quantity of pallidal neurons uncoupled to cortical activity was observed to significantly decrease in 6-OHDA lesioned rats compared to controls. Behaviorally, raclopride (5 μg/kg, i.p.) was found to significantly potentiate the therapeutic benefit of L-DOPA (3 mg/kg, i.p.)

Inhibition and oscillatory activity in human motor cortex

Using transcranial magnetic stimulation (TMS) important information can be obtained about the function of motor cortical circuitry during performance of voluntary movements by conscious human subjects. In particular, pairs of TMS pulses can probe inhibitory pathways projecting onto corticospinal neurones, which themselves project to motoneurones innervating hand muscles. This allows investigation of inhibitory circuitry involved in the performance of specific motor tasks, such as the precision grip. Previous studies have shown that pronounced synchronous oscillatory activity within the hand motor system is present at both cortical and muscular level when subjects maintain steady grasp of an object in a precision grip. The origin of this synchronous activity is unknown. However modelling studies have suggested that inhibitory pathways are likely to play an important role in the generation of cortical oscillations, and therefore TMS was used in this Thesis to investigate the origin of synchrony present during the precision grip task. In the first study, parameters of the paired-pulse test used to measure intracortical inhibition were examined. It was found that by modifying the intensities of the stimuli, and the interval between the paired-pulses, different phases of inhibition could be measured. This enabled specific use of TMS to investigate inhibitory pathways. Both single and paired-pulse TMS were then delivered to the motor cortex of subjects performing a precision grip task. It was found that low intensity TMS could reset the phase of muscle oscillatory activity, consistent with corticospinal neurones being part of the circuitry that generates the oscillatory rhythm. When, in the paired-pulse test, a low intensity stimulus was followed a few milliseconds later with a larger TMS stimulus, in the paired-pulse test, strong intracortical inhibition could be measured. This suggested that inhibitory interneurones activated by low intensity TMS could play an important role in the rhythm-generating network. An additional study looked at the importance of cutaneous receptor feedback on synchrony, by studying the effects of local anaesthesia of the index finger and thumb. Whereas low intensity TMS was shown to enhance synchronous activity between muscle pairs, suppression of cutaneous feedback from the digits reduced it. Results in this Thesis suggest that inhibitory interneurones within the motor cortex are important in the generation of synchronous activity within the hand motor system. This synchrony is also under the influence of cutaneous afferent input

Mean-field analysis of basal ganglia and thalamocortical dynamics

When modeling a system as complex as the brain, considerable simplifications are inevitable. The nature of these simplifications depends on the available experimental evidence, and the desired form of model predictions. A focus on the former often inspires models of networks of individual neurons, since properties of single cells are more easily measured than those of entire populations. However, if the goal is to describe the processes responsible for the electroencephalogram (EEG), such models can become unmanageable due to the large numbers of neurons involved. Mean-field models in which assemblies of neurons are represented by their average properties allow activity underlying the EEG to be captured in a tractable manner. The starting point of the results presented here is a recent physiologically-based mean-field model of the corticothalamic system, which includes populations of excitatory and inhibitory cortical neurons, and an excitatory population representing the thalamic relay nuclei, reciprocally connected with the cortex and the inhibitory thalamic reticular nucleus. The average firing rates of these populations depend nonlinearly on their membrane potentials, which are determined by afferent inputs after axonal propagation and dendritic and synaptic delays. It has been found that neuronal activity spreads in an approximately wavelike fashion across the cortex, which is modeled as a two-dimensional surface. On the basis of the literature, the EEG signal is assumed to be roughly proportional to the activity of cortical excitatory neurons, allowing physiological parameters to be extracted by inverse modeling of empirical EEG spectra. One objective of the present work is to characterize the statistical distributions of fitted model parameters in the healthy population. Variability of model parameters within and between individuals is assessed over time scales of minutes to more than a year, and compared with the variability of classical quantitative EEG (qEEG) parameters. These parameters are generally not normally distributed, and transformations toward the normal distribution are often used to facilitate statistical analysis. However, no single optimal transformation exists to render data distributions approximately normal. A uniformly applicable solution that not only yields data following the normal distribution as closely as possible, but also increases test-retest reliability, is described in Chapter 2. Specialized versions of this transformation have been known for some time in the statistical literature, but it has not previously found its way to the empirical sciences. Chapter 3 contains the study of intra-individual and inter-individual variability in model parameters, also providing a comparison of test-retest reliability with that of commonly used EEG spectral measures such as band powers and the frequency of the alpha peak. It is found that the combined model parameters provide a reliable characterization of an individual's EEG spectrum, where some parameters are more informative than others. Classical quantitative EEG measures are found to be somewhat more reproducible than model parameters. However, the latter have the advantage of providing direct connections with the underlying physiology. In addition, model parameters are complementary to classical measures in that they capture more information about spectral structure. Another conclusion from this work was that a few minutes of alert eyes-closed EEG already contain most of the individual variability likely to occur in this state on the scale of years. In Chapter 4, age trends in model parameters are investigated for a large sample of healthy subjects aged 6-86 years. Sex differences in parameter distributions and trends are considered in three age ranges, and related to the relevant literature. We also look at changes in inter-individual variance across age, and find that subjects are in many respects maximally different around adolescence. This study forms the basis for prospective comparisons with age trends in evoked response potentials (ERPs) and alpha peak morphology, besides providing a standard for the assessment of clinical data. It is the first study to report physiologically-based parameters for such a large sample of EEG data. The second main thrust of this work is toward incorporating the thalamocortical system and the basal ganglia in a unified framework. The basal ganglia are a group of gray matter structures reciprocally connected with the thalamus and cortex, both significantly influencing, and influenced by, their activity. Abnormalities in the basal ganglia are associated with various disorders, including schizophrenia, Huntington's disease, and Parkinson's disease. A model of the basal ganglia-thalamocortical system is presented in Chapter 5, and used to investigate changes in average firing rates often measured in parkinsonian patients and animal models of Parkinson's disease. Modeling results support the hypothesis that two pathways through the basal ganglia (the so-called direct and indirect pathways) are differentially affected by the dopamine depletion that is the hallmark of Parkinson's disease. However, alterations in other components of the system are also suggested by matching model predictions to experimental data. The dynamics of the model are explored in detail in Chapter 6. Electrophysiological aspects of Parkinson's disease include frequency reduction of the alpha peak, increased relative power at lower frequencies, and abnormal synchronized fluctuations in firing rates. It is shown that the same parameter variations that reproduce realistic changes in mean firing rates can also account for EEG frequency reduction by increasing the strength of the indirect pathway, which exerts an inhibitory effect on the cortex. Furthermore, even more strongly connected subcircuits in the indirect pathway can sustain limit cycle oscillations around 5 Hz, in accord with oscillations at this frequency often observed in tremulous patients. Additionally, oscillations around 20 Hz that are normally present in corticothalamic circuits can spread to the basal ganglia when both corticothalamic and indirect circuits have large gains. The model also accounts for changes in the responsiveness of the components of the basal ganglia-thalamocortical system, and increased synchronization upon dopamine depletion, which plausibly reflect the loss of specificity of neuronal signaling pathways in the parkinsonian basal ganglia. Thus, a parsimonious explanation is provided for many electrophysiological correlates of Parkinson's disease using a single set of parameter changes with respect to the healthy state. Overall, we conclude that mean-field models of brain electrophysiology possess a versatility that allows them to be usefully applied in a variety of scenarios. Such models allow information about underlying physiology to be extracted from the experimental EEG, complementing traditional measures that may be more statistically robust but do not provide a direct link with physiology. Furthermore, there is ample opportunity for future developments, extending the basic model to encompass different neuronal systems, connections, and mechanisms. The basal ganglia are an important addition, not only leading to unified explanations for many hitherto disparate phenomena, but also contributing to the validation of this form of modeling

SYNAPTIC PLASTICITY AND SENSORY INFORMATION ROCESSING THROUGH THE THALAMUS AND THE CORTEX OF THE RODENT BARREL FIELD

Sensory information processing is a key process in the brain because it involves many sensory inputs. Some of them are relevant and should induce a motor or cognitive response. In addition, many irrelevant stimuli reach sensory pathway and should be ignored. Synaptic plasticity in the central nervous system is a general process that enhances or decreases sensory responses according to the temporal pattern of stimuli. My main aim is to study synaptic plas- ticity in the somatosensory pathway, mainly in the thalamo-cortical loop. Sensory information from rodent whiskers is sent from the whisker follicle to the contralateral area of the thalamus and from the thalamus to the barrel cortex (BC). In this Doctoral Thesis we performed extracel- lular in vivo recordings in the BC and thalamus of urethane anesthetized rats and mice in order to unravel the mechanisms of synaptic plasticity and sensory processing. We observed that repetitive stimulation at frequencies at which the animal explores the environment induced long-term potentiation (LTP). In addition, low frequency stimulation could induce LTP or long-term depression (LTD) depending on the intracellular Ca2+ concentration during the stimulation time period. This long-term plasticity depended on NMDA receptors activation and the activation of muscarinic and nicotinic cholinergic receptors. Through an optogenetic study we showed that the basal forebrain (BF), the main source of acetylcholine (Ach) to the neocortex, sent its projections in an organized way. Consequently, the Ach-depending facilitation of cortical responses occurs in a very specific manner. We also found that the postero-medial thalamic nucleus (POM) regulated BC whisker responses through GABAergic (γ-aminobutyric-acid: GABA) neurons located in upper cortical layers. -- Le traitement de l’information sensorielle est un processus clef dans le cerveau parce qu’il reçoit de nombreux inputs sensoriels. Certains d’entre eux sont pertinents et devraient provo- quer une réponse motrice ou sensorielle. La plasticité synaptique dans le système nerveux central est un processus général qui améliore ou réduit les réponses sensorielles selon le circuit temporel des stimuli. L’information sensorielle des vibrisses des rongeurs est envoyée depuis le follicule de la vibrisse jusqu’à la zone contralatérale du thalamus et du thalamus jusqu’au cortex somato-sensoriel (BC). Au cours de cette thèse de doctorat nous avons effectué des enregistrements extra-cellulaires in vivo dans le BC et le thalamus de rats et souris anesthésiés à l’uréthane afin de découvrir les mécanismes de la plasticité synaptique et du traitement sensoriel. Nous avons observé qu’une stimulation répétée à des fréquences auxquelles l’ani- mal explore son environnement provoquait une potentialisation à long terme (LTP). De plus, une stimulation à basse fréquence peut provoquer une LTP ou une dépression à long terme (LTD) selon la concentration intra-cellulaire de Ca2+ pendant la durée de la stimulation. Cette plasticité à long terme dépend de l’activation des récepteurs NMDA et de l’activation des récepteurs cholinergiques muscariniques et nicotiniques. Grâce à une étude optogénétique nous avons pu montrer que le prosencéphale basal (BF), la source principale d’acetylcholine (Ach) vers le cortex, envoyait ses projections de façon organisée. Par conséquent, la facilitation des réponses corticales dépendant de l’Ach se produit de manière très spécifique. Nous avons également découvert que le noyau thalamique postéro-médial (POM) régulait la vibrisse du BC grâce à des neurones GABAergiques situés dans les couches supérieures du cortex. -- El procesamiento de la información sensorial es un proceso clave en el cerebro ya que involu- cra varios inputs sensoriales. Algunos de ellos son relevantes e inducen respuestas motoras o cognitivas. Además, muchos estímulos irrelevantes alcanzan la via sensorial y deben ser descartados. La plasticidad sináptica en el sistema nervios central es un proceso que aumenta o deprime las respuestas sensoriales según un patrón temporal de estimulación. Mi objetivo principal es estudiar la plasticidad sináptica en la via somatosensorial principalmente en el circuito tálamo-cortex. La información sensorial de las vibrisas de los roedores viaja del folículo de estas a la zona contralateral del tálamo, y desde esta a la corteza de barriles (BC). En esta Tesis Doctoral hicimos registros extracelulares in vivo en la BC y el tálamo en ratas y ratones anestesiados con uretano con el objetivo de conocer los mecanismos de la plasti- cidad sináptica y el procesamiento sensorial en esta vía. Observamos que una estimulación repetitiva a las frecuencias a las cuales el animal explora su entorno, inducen potenciación a largo plazo (LTP). Además, la estimulación a baja frecuencia pudo inducir LTP o depresión a largo plazo (LTD) dependiendo del la concentración de Ca2+ intracellular durante el periodo de estimulación. Mediante un estudio de optogenética, observamos que el prosencefalo basal (BF), el núcleo que surte principalmente a la corteza de acetilcolina (Ach) manda proyecciones de forma organizada. Encontramos tambien que el núcleo posterior-medial del talamo (POM) regula la respuesta de la corteza de barriles a traves de las neuronas GABAérgicas de la capa I

Synaptic plasticity and sensory information processing through the thalamus and the cortex of the rodent barrel field

Tesis doctoral inédita cotutelada por l´Université de Lausanne y la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Anatomía, Histología y Neurociencia. Fecha de lectura: 26-06-2017Le traitement de l’information sensorielle est un processus clef dans le cerveau parce qu’il reçoit de nombreux inputs sensoriels. Certains d’entre eux sont pertinents et devraient provoquer une réponse motrice ou sensorielle. La plasticité synaptique dans le système nerveux central est un processus général qui améliore ou réduit les réponses sensorielles selon le circuit temporel des stimuli. L’information sensorielle des vibrisses des rongeurs est envoyée depuis le follicule de la vibrisse jusqu’à la zone contralatérale du thalamus et du thalamus jusqu’au cortex somato-sensoriel (BC). Au cours de cette thèse de doctorat nous avons effectué des enregistrements extra-cellulaires in vivo dans le BC et le thalamus de rats et souris anesthésiés à l’uréthane afin de découvrir les mécanismes de la plasticité synaptique et du traitement sensoriel. Nous avons observé qu’une stimulation répétée à des fréquences auxquelles l’animal explore son environnement provoquait une potentialisation à long terme (LTP). De plus, une stimulation à basse fréquence peut provoquer une LTP ou une dépression à long terme (LTD) selon la concentration intra-cellulaire de Ca2+ pendant la durée de la stimulation. Cette plasticité à long terme dépend de l’activation des récepteurs NMDA et de l’activation des récepteurs cholinergiques muscariniques et nicotiniques. Grâce à une étude optogénétique nous avons pu montrer que le prosencéphale basal (BF), la source principale d’acetylcholine (Ach) vers le cortex, envoyait ses projections de façon organisée. Par conséquent, la facilitation des réponses corticales dépendant de l’Ach se produit demanière très spécifique. Nous avons également découvert que le noyau thalamique postéro-médial (POM) régulait la vibrisse du BC grâce à des neurones GABAergiques situés dans les couches supérieures du cortex. Mot clefs : cortex somato-sensoriel, thalamus, plasticité synaptique, récepteurs NMDA, acetylcholineEl procesamiento de la información sensorial es un proceso clave en el cerebro ya que involucra varios inputs sensoriales. Algunos de ellos son relevantes e inducen respuestas motoras o cognitivas. Además, muchos estímulos irrelevantes alcanzan la via sensorial y deben ser descartados. La plasticidad sináptica en el sistema nervios central es un proceso que aumenta o deprime las respuestas sensoriales según un patrón temporal de estimulación.Mi objetivo principal es estudiar la plasticidad sináptica en la via somatosensorial principalmente en el circuito tálamo-cortex. La información sensorial de las vibrisas de los roedores viaja del folículo de estas a la zona contralateral del tálamo, y desde esta a la corteza de barriles (BC). En esta Tesis Doctoral hicimos registros extracelulares in vivo en la BC y el tálamo en ratas y ratones anestesiados con uretano con el objetivo de conocer los mecanismos de la plasticidad sináptica y el procesamiento sensorial en esta vía. Observamos que una estimulación repetitiva a las frecuencias a las cuales el animal explora su entorno, inducen potenciación a largo plazo (LTP). Además, la estimulación a baja frecuencia pudo inducir LTP o depresión a largo plazo (LTD) dependiendo del la concentración de Ca2+ intracellular durante el periodo de estimulación.Mediante un estudio de optogenética, observamos que el prosencefalo basal (BF), el núcleo que surte principalmente a la corteza de acetilcolina (Ach) manda proyecciones de forma organizada. Encontramos tambien que el núcleo posterior-medial del talamo (POM) regula la respuesta de la corteza de barriles a traves de las neuronas GABAérgicas de la capa I. Palabras clave: corteza somatosensorial, tálamo, plasticidad sináptica, receptores NMDA, acetilcolin