Thesis (Ph.D. in Pharmacology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 100-118).

Grundtanken med detta arbete är att se om utomhuspedagogik möjligtvis främjar lärandet och om det går att finna stöd inom neurologisk forskning för att ta reda på om lärandet stimuleras vid användandet av utomhusundervisning. Undersökningar har genomförts för att se om lärare och elevers syn på utomhusundervisning sammanfaller. Arbetet bygger på litteraturstudier, intervjuer, en observationsstudie, samt enkätundersökningar för att besvara forskningsfrågorna. I denna studie har det framkommit att utomhusundervisning främjar lärandet, främst beroende på de multipla sinnesintryck som utomhusvistelsen skapar. Denna iakttagelse stöds även av neurologisk och pedagogisk forskning. Det har även framkommit att lärare och elever tycker att utomhusundervisning är ett viktigt och positivt inslag i undervisningen.

no / Age is characterized by deficits in synaptic function identified by decreased performance of aged animals in spatial learning tasks and reduced ability of animals to sustain long-term potentiation (LTP). Several cellular and molecular events are correlated with these deficits, many of which are indicative of cell stress. Thus there is evidence of age-related neuroinflammatory stress and oxidative stress and these have been linked with microglial activation which is likely to be primarily responsible for the age-related increase in production of proinflammatory cytokines and reactive oxygen species. It is significant that agents which decrease microglial activation are commonly associated with restoration of function. We set out to examine whether the n-3 polyunsaturated fatty acid docosapentaenoic acid (DPA), which is a metabolite of eicosapentaenoic acid (EPA), could modulate the age-related increase in microglial activation and the associated increase in oxidative changes and therefore impact on synaptic function in aged rats. We demonstrate that DPA possesses neurorestorative effects and is capable of downregulating microglial activation. The data show that it also decreases the coupled activation of sphingomyelinase and caspase 3, probably as a result of its ability to decrease age-related oxidative changes, and consequently attenuates the age-related decrease in spatial learning and LTP.

Long-term potentiation (LTP) and depression (LTD) are activity dependent long-lasting changes in synaptic efficacy and have been proposed as mechanisms for learning and memory. Although the exact relationship of LTP and LTD to memory is not known, they do share some properties and mechanisms that relate to memory, such as the strengthening and weakening of synapses. LTP and LTD have been studied extensively in hippocampal brain-slice preparations, due to its relatively organized structure, ease of induction, and its critical function in memory storage. Less work has been done in the neocortex despite the belief that it is heavily involved in the storage of long-term memories. Activity dependent plasticity has also been demonstrated in the basal ganglia in vivo and in vitro, but the results have been somewhat inconsistent. The experiments presented in this thesis explore a novel form of neural plasticity in two excitatory pathways (corticostriatal and thalamocortical) of the basal ganglia motor loop in the intact brain in awake, freely behaving rats. In thalamocortical slice preparations, simultaneous presynaptic stimulation and postsynaptic depolarization can induce L TP in animals prior to the critical period. However the results presented in this thesis show that applied stimulation to the thalamocortical pathway failed to produce either LTP or LTD in the awake freely moving animal.Corticostriatal LTD has been shown in slice preparations following direct tetanic stimulation of the striatum. In the current experiment, cortical stimulation failed to induce LTD although there was an observable decrease in the evoked potential following low-frequency stimulation. Corticostriatal L TP has been shown to depend on the type of stimulation applied. High-frequency and theta burst stimulation produced long-lasting changes in response amplitude in the corticostriatal pathway, with theta burst stimulation appearing to be the more effective stimulation protocol for inducing LTP in both the early and late components. Paired stimulation of the substantia nigra pars compacta and cortex indicated a modulatory action of dopamine on corticostriatal synaptic plasticity. Pairing led to a stable increase in the amplitude of LTP of both early and late components. We also report that a temporal relationship exists in the striatum with respect to the release of nigral dopamine and cortical glutamate. Simultaneous stimulation produced a more robust L TP compared to the two other conditions in which there was an applied stimulation delay to either the corticostriatal or nigrostriatal pathway. The results demonstrate the mechanistic differences, not only between the thalamocortical and corticostriatal pathways, but also slice and anesthetized preparations. The results also emphasize the need for further study on mechanisms of L TP and LTD in the various excitatory and inhibitory pathways of the basal ganglia motor loop. / Thesis / Doctor of Philosophy (PhD)

Xie, Hui. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 91-116). / Abstracts in English and Chinese. / CONTENTS --- p.I / ACKNOWLEDGEMENTS --- p.i / ABSTRACT --- p.ii / 中文摘要 --- p.v / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- Overview of the Study --- p.1 / Chapter 1.2 --- Obstructive Sleep Apnea --- p.4 / Chapter 1.2.1 --- Epidemiology --- p.5 / Chapter 1.2.1.1 --- Prevalence --- p.5 / Chapter 1.2.1.2 --- Risk Factors --- p.6 / Chapter 1.2.2 --- Pathogenesis --- p.8 / Chapter 1.2.3 --- Pathophysiologic Consequences --- p.9 / Chapter 1.2.4 --- Diagnosis --- p.12 / Chapter 1.2.5 --- Treatment --- p.13 / Chapter 1.3 --- Memory and Long-term Potentiation --- p.15 / Chapter 1.3.1 --- Memory --- p.15 / Chapter 1.3.1.1 --- Classification of Memory --- p.15 / Chapter 1.3.1.1 --- Physiology of Memory --- p.17 / Chapter 1.3.2 --- Hippocampus --- p.18 / Chapter 1.3.2.1 --- Anatomy --- p.18 / Chapter 1.3.2.2 --- Hippocampus and Memory --- p.20 / Chapter 1.3.3 --- Long-term Potentiation (LTP) --- p.20 / Chapter 1.3.3.1 --- Discovery of LTP --- p.21 / Chapter 1.3.3.2 --- Types of LTP --- p.22 / Chapter 1.3.3.3 --- Properties of NMDA-LTP --- p.23 / Chapter 1.3.3.4 --- Early Phase LTP and Mechanism --- p.24 / Chapter 1.3.3.5 --- Late Phase LTP and Mechanism --- p.28 / Chapter 1.3.3.6 --- Important Factors in Long-term Potentiation --- p.29 / Chapter 1.4 --- Brain-derived Neurotrophic Factor (BDNF) --- p.33 / Chapter 1.4.1 --- Neurotrophins --- p.33 / Chapter 1.4.2 --- Structure and Expression of BDNF --- p.36 / Chapter 1.4.3 --- BDNF and Synaptic Plasticity --- p.37 / Chapter 1.4.3.1 --- BDNF and E-LTP --- p.38 / Chapter 1.4.3.2 --- BDNF and L-LTP --- p.39 / Chapter CHAPTER 2 --- METHODS --- p.43 / Chapter 2.1 --- Animal model of Obstructive Sleep Apnea --- p.43 / Chapter 2.1.1 --- Chronic Intermittent Hypoxia --- p.43 / Chapter 2.1.2 --- Bodyweight During Hypoxia Treatment --- p.47 / Chapter 2.2 --- Electrophysiological Experiments --- p.47 / Chapter 2.2.1 --- Brain Slice Preparation --- p.47 / Chapter 2.2.2 --- Multi-electrode Recording Setup (MED64) --- p.48 / Chapter 2.2.3 --- Slice Superfusion --- p.51 / Chapter 2.3.4 --- Field Potential Recordings --- p.53 / Chapter 2.3.5 --- LTP Induction Protocol --- p.55 / Chapter 2.3 --- Stereotaxic Surgery --- p.57 / Chapter 2.4 --- Drugs and Data Analysis --- p.58 / Chapter CHAPTER 3 --- RESULTS --- p.59 / Chapter 3.1 --- Validation of the OSA model --- p.59 / Chapter 3.2 --- Optimization for Studies of Early and Late-phase LTP by MED64 --- p.60 / Chapter 3.2.1 --- Optimization of Brain Slices --- p.60 / Chapter 3.2.2 --- Optimization of Field Potential Recording --- p.62 / Chapter 3.2.3 --- Optimization for LTP Study --- p.65 / Chapter 3.3 --- Effect of Intermittent Hypoxia on Hippocampal LTP --- p.68 / Chapter 3.3.1 --- Early-phase LTP (E-LTP) --- p.68 / Chapter 3.3.2 --- Late-phase LTP (L-LTP) --- p.71 / Chapter 3.4 --- Effect of BDNF on Intermittent Hypoxia-induced LTP Impairment --- p.75 / Chapter 3.4.1 --- BDNF Rescues LTP Impairment --- p.75 / Chapter 3.4.2 --- BDNF prevents LTP Impairment --- p.78 / Chapter CHAPTER 4 --- DISCUSSION --- p.80 / Chapter 4.1 --- Chronic Intermittent Hypoxia Model of OSA in Mice --- p.80 / Chapter 4.2 --- Impairment of LTP Induced by Intermittent Hypoxia --- p.82 / Chapter 4.3 --- The role of BDNF in IH-induced Impairment in Hippocampal Synaptic Plasticity --- p.84 / Chapter 4.4 --- Future Studies --- p.89 / REFERENCE --- p.91

Conventional functional electrical stimulation (FES) therapy, if provided shortly after an incomplete spinal cord injury, is able to help an individual to restore voluntary hand function. This is thought to occur through the induction of neuroplasticity. However, conventional FES therapy employs a push-button-based control scheme, which does not fully require the recipient to generate volitional movements. The first study in this thesis therefore sought to determine, in an early proof-of-concept test with able-bodied participants, whether control strategies which are triggered by volitional activity (including an electroencephalography-based brain-machine interface (BMI-FES) and an electromyogram-based control scheme (EMG-FES)) might provide greater benefits to hand function. The results offer relatively weak evidence to suggest that BMI-FES, and especially EMG-FES, were able to induce greater neuroplasticity than conventional treatments in the corticospinal tract leading to the hands, but that this did not immediately translate to more functional improvements such as maximum grip force. ii The second study in this thesis focussed on spinal associative stimulation (SAS), which involves paired stimulation pulses at both the head (via transcranial magnetic stimulation), and the wrist (via peripheral nerve stimulation). The purpose of this, as with the first study, was to induce neuroplasticity and upregulate the corticospinal tract leading to the hands. While limited research has suggested that it is possible to produce neuroplasticity through SAS, all such studies have provided stimulation at a fixed frequency of 0.1 or 0.2 Hz. The present study therefore sought to compare the effectiveness of a typical 0.1 Hz paradigm with a 1 Hz paradigm, and a paradigm which provided stimulation in 5 Hz “bursts”. None of the paradigms were able to successfully induce neuroplasticity in a consistent manner. The increased variability in this study as compared to the previous one, despite the nearly identical assessment methodology, suggests that responses to the SAS treatment may have been highly individual. This serves to highlight a potential limitation of the treatment, which is that its effectiveness may not be universal, but rather dependent on each specific recipient. This may be a challenge faced by SAS should it continue to be tested as a novel therapy.

Thesis (Ph.D. in Neuroscience) -- University of Colorado Denver, 2007. / Typescript. Includes bibliographical references (leaves 200-233). Free to UCD affiliates. Online version available via ProQuest Digital Dissertations;

Synaptic plasticity is thought to be integral to learning and memory. The two most common forms of plasticity are long-term potentiation (LTP) and long-term depression (LTD), both of which can be supported either by presynaptic changes in transmitter release probability (Pr), or by postsynaptic changes in AMPA receptor number. It is generally thought that the induction of LTP and LTD at Schaffer-collateral synapses in the hippocampus depends on the activation of NMDA receptors (GluN). Recent studies, however, have demonstrated that both increases and decreases in Pr can be induced under blockade of postsynaptic GluN receptors, suggesting that the activation of postsynaptic GluN receptors by glutamate is only a strict requirement for postsynaptic plasticity. In this thesis, I therefore re-examined the role of glutamate in presynaptic plasticity. I used single synapse imaging along with electrophysiological and pharmacological techniques to independently manipulate and monitor the levels of glutamatergic signalling during synaptic activity. I discovered that glutamate is inhibitory and unnecessary for the induction of LTP at the presynaptic locus. My findings support a novel model of presynaptic plasticity in which the net activity-dependent changes in Pr at an active presynaptic terminal is jointly determined by two opposing processes that can be simultaneously active: 1) postsynaptic depolarization, which, via the activation of L-type voltage-gated Ca²⁺ channels, increases Pr by driving the synthesis and release of nitric oxide from neuronal dendrites and 2) glutamate release, which through the activation of presynaptic GluN receptors, decreases Pr. Computationally, this model suggests that plasticity functions to reduce prediction-errors that arise during synaptic activity, and, thereby offers a biologically plausible mechanism by which neuronal networks may optimize learning at the level of single synapses.

A sinalização muscarínica exerce função modulatória sobre diferentes aspectos da cognição e emoções. Todos os cinco subtipos de receptores muscarínicos (mAChR), M1 a M5, são expressos no hipocampo de mamíferos e são ativados de forma sobreposta pela maioria dos fármacos, dificultando avanços significativos na compreensão da contribuição de cada componente desse sistema. A toxina muscarínica 3 (MT3) é um antagonista seletivo para o subtipo M4, permitindo a investigação das ações modulatórias deste receptor no aprendizado, memória e plasticidade sináptica. Os M4 são receptores acoplados à proteína G (GPCRs) que atuam via Gi/o desencadeando efeitos inibitórios sobre as células em que estão presentes. Estudos comportamentais anteriores indicam que a administração de MT3 imediatamente após o treino em uma tarefa aversiva produz efeito amnéstico, enquanto que a administração antes da evocação, causa facilitação. Uma explicação para estes resultados é que os circuitos locais envolvidos na consolidação e na evocação da memória diferem em sua natureza. Nesse contexto, sugere-se que o efeito amnéstico da MT3 sobre a consolidação seja consequência da supressão da inibição de interneurônios GABAérgicos; enquanto que na evocação, esse efeito se daria sobre as sinapses glutamatérgicas. Assim, no presente trabalho, com o objetivo de investigar como o receptor M4 modula a plasticidade sináptica de longa duração e interage com uma dessas sinalizações, no caso a GABAérgica, utilizou-se a técnica de eletrofisiologia in vivo de hipocampo de ratos anestesiados. Para tanto, foram realizados registros extracelulares do potencial excitatório pós-sináptico de campo (fEPSP) de CA1 evocados por estimulação contralateral da via Colateral de Schaffer com infusão dos fármacos 15 min antes ou depois da estimulação elétrica de alta ou baixa frequência (HFS: 10 trens 0,5 Hz, 20 pulsos 100 Hz; ou LFS: 600 pulsos 1 Hz, respectivamente). MT3 (4,0 μg/μl), bicuculina (0,06 μg/μl), baclofen (0,2 μg/μl) e veículo, isoladamente ou combinados, não alteraram a amplitude da resposta evocada basal ou a facilitação por pulso pareado (FPP) 15 min após a infusão. MT3 aparentemente atenuou, mas não de forma significativa, a potenciação de longa duração (LTP) em relação ao controle (potenciação 60 min após a HFS de 31,8% e 66,0%, respectivamente). Além disso, não houve diferença significativa entre a amplitude do fEPSP no período basal e 60 min após a HFS sob ação da MT3. Bicuculina, embora não tenha abolido a LTP e nem causado alteração na FPP, produziu uma potenciação de apenas 36,4%. Baclofen promoveu uma potenciação semelhante à dos controles. A administração de baclofen também reduziu significativamente a FPP em relação ao basal. A administração conjunta de MT3 com bicuculina ou baclofen promoveu uma potenciação semelhante ao controle. MT3 não apresentou efeito sobre a manutenção da LTP quando aplicada 15 min após a HFS. Por fim, não foi possível induzir a depressão de longa duração (LTD) com o protocolo de LFS utilizado. Embora não tenha ocorrido diferença estatisticamente significativa entre os grupos devido ao baixo número de animais utilizados, os dados sugerem a possibilidade de uma amplitude reduzida da LTP quando da injeção de bicuculina. Baclofen alterou a FPP em relação ao fEPSP basal, o mesmo não tendo sido observado no grupo controle. Com a administração concomitante de MT3, tais alterações deixam de ser identificadas. Ainda que os achados experimentais sejam inconclusivos e preliminares, este trabalho permitiu a padronização da técnica de eletrofisiologia in vivo em animal anestesiado o que abre portas para futuras investigações. / The cholinergic muscarinic system exerts modulatory function over different aspects of cognition and emotion. All five muscarinic receptors subtypes (mAChR), M1 to M5, are expressed at mammals hippocampus and at least two of them are simultaneously activated by most of the drugs, hindering significant advances on the role of each component of this system. The muscarinic toxin 3 (MT3) is a selective antagonist for the M4 subtype, allowing the investigation of the modulatory actions of this receptor over learning, memory and synaptic plasticity. The M4 are G protein coupled receptors (GPCRs) that act through Gi/o triggering inhibitory effects on which cells they are occur. Previous behavioral studies have shown that administration of MT3 soon after aversive task training exerts amnestic effects over memory, while administration prior to recall, leads to facilitation. A possible explanation to these results could be that the local circuits involved on memory consolidation and recall are different in nature. On this perspective, the amnestic effect of MT3 over memory consolidation should be consequence of GABAergic interneurons inhibition suppression; while the effect on recall, should be over glutamatergic synapses modulation. Thereby, the present work, with the objective to investigate how the M4 receptor modulates long-term synaptic plasticity and interacts with the GABAergic system, in vivo electrophysiological approach of anesthetized rats’ hippocampus was applied. Hence, field excitatory postsynaptic potentials (fEPSP) from CA1 were recorded after stimulation of contralateral Schaffer Collateral pathway with drugs infusion 15 min before or after high or low frequency electric stimulation (HFS: 10 trains 0.5 Hz, 20 pulses 100 Hz; LFS: 600 pulses 1 Hz, respectively). Neither MT3 (4.00 μg/μl), bicuculline (0.06 μg/μl), baclofen (0.20 μg/μl) nor vehicle, isolated or combined, changed the baseline evoked response amplitude 15 min after infusion nor the paired-pulse facilitation ratio (PPF). MT3 apparently attenuated, but not significantly, the long-term potentiation (LTP) compared to control (31.8% and 66.0% potentiation 60 min after HFS, respectively). In addition, there was no significant difference between baseline and 60 min after HFS fEPSP amplitude at MT3 group. Bicuculline, although did not abolish LTP neither changed PPF, it did produce a potentiation of only 36.4%. Baclofen induced a potentiation similar to control group. Baclofen administration also significantly reduced PPF compared to baseline. The simultaneous administration of MT3 and bicuculline or baclofen led to a potentiation similar to the control group. MT3 did not show any effect over LTP maintenance when applied 15 min after HFS. Lastly, it was not possible to induce long-term depression (LTD) with the used LFS protocol. Although there was no statistical significance between groups due to the low animal numbers used, data suggest that bicuculline had reduced LTP amplitude. Baclofen did alter PPF and the same was not observed on control group. When bicuculline or baclofen were injected with MT3, those alterations were not observed. These are inconclusive and preliminary results, notwithstanding this work allowed to set up the in vivo electrophysiology technique in anesthetized animals what will provide new tools for future research.

A sinalização muscarínica exerce função modulatória sobre diferentes aspectos da cognição e emoções. Todos os cinco subtipos de receptores muscarínicos (mAChR), M1 a M5, são expressos no hipocampo de mamíferos e são ativados de forma sobreposta pela maioria dos fármacos, dificultando avanços significativos na compreensão da contribuição de cada componente desse sistema. A toxina muscarínica 3 (MT3) é um antagonista seletivo para o subtipo M4, permitindo a investigação das ações modulatórias deste receptor no aprendizado, memória e plasticidade sináptica. Os M4 são receptores acoplados à proteína G (GPCRs) que atuam via Gi/o desencadeando efeitos inibitórios sobre as células em que estão presentes. Estudos comportamentais anteriores indicam que a administração de MT3 imediatamente após o treino em uma tarefa aversiva produz efeito amnéstico, enquanto que a administração antes da evocação, causa facilitação. Uma explicação para estes resultados é que os circuitos locais envolvidos na consolidação e na evocação da memória diferem em sua natureza. Nesse contexto, sugere-se que o efeito amnéstico da MT3 sobre a consolidação seja consequência da supressão da inibição de interneurônios GABAérgicos; enquanto que na evocação, esse efeito se daria sobre as sinapses glutamatérgicas. Assim, no presente trabalho, com o objetivo de investigar como o receptor M4 modula a plasticidade sináptica de longa duração e interage com uma dessas sinalizações, no caso a GABAérgica, utilizou-se a técnica de eletrofisiologia in vivo de hipocampo de ratos anestesiados. Para tanto, foram realizados registros extracelulares do potencial excitatório pós-sináptico de campo (fEPSP) de CA1 evocados por estimulação contralateral da via Colateral de Schaffer com infusão dos fármacos 15 min antes ou depois da estimulação elétrica de alta ou baixa frequência (HFS: 10 trens 0,5 Hz, 20 pulsos 100 Hz; ou LFS: 600 pulsos 1 Hz, respectivamente). MT3 (4,0 μg/μl), bicuculina (0,06 μg/μl), baclofen (0,2 μg/μl) e veículo, isoladamente ou combinados, não alteraram a amplitude da resposta evocada basal ou a facilitação por pulso pareado (FPP) 15 min após a infusão. MT3 aparentemente atenuou, mas não de forma significativa, a potenciação de longa duração (LTP) em relação ao controle (potenciação 60 min após a HFS de 31,8% e 66,0%, respectivamente). Além disso, não houve diferença significativa entre a amplitude do fEPSP no período basal e 60 min após a HFS sob ação da MT3. Bicuculina, embora não tenha abolido a LTP e nem causado alteração na FPP, produziu uma potenciação de apenas 36,4%. Baclofen promoveu uma potenciação semelhante à dos controles. A administração de baclofen também reduziu significativamente a FPP em relação ao basal. A administração conjunta de MT3 com bicuculina ou baclofen promoveu uma potenciação semelhante ao controle. MT3 não apresentou efeito sobre a manutenção da LTP quando aplicada 15 min após a HFS. Por fim, não foi possível induzir a depressão de longa duração (LTD) com o protocolo de LFS utilizado. Embora não tenha ocorrido diferença estatisticamente significativa entre os grupos devido ao baixo número de animais utilizados, os dados sugerem a possibilidade de uma amplitude reduzida da LTP quando da injeção de bicuculina. Baclofen alterou a FPP em relação ao fEPSP basal, o mesmo não tendo sido observado no grupo controle. Com a administração concomitante de MT3, tais alterações deixam de ser identificadas. Ainda que os achados experimentais sejam inconclusivos e preliminares, este trabalho permitiu a padronização da técnica de eletrofisiologia in vivo em animal anestesiado o que abre portas para futuras investigações. / The cholinergic muscarinic system exerts modulatory function over different aspects of cognition and emotion. All five muscarinic receptors subtypes (mAChR), M1 to M5, are expressed at mammals hippocampus and at least two of them are simultaneously activated by most of the drugs, hindering significant advances on the role of each component of this system. The muscarinic toxin 3 (MT3) is a selective antagonist for the M4 subtype, allowing the investigation of the modulatory actions of this receptor over learning, memory and synaptic plasticity. The M4 are G protein coupled receptors (GPCRs) that act through Gi/o triggering inhibitory effects on which cells they are occur. Previous behavioral studies have shown that administration of MT3 soon after aversive task training exerts amnestic effects over memory, while administration prior to recall, leads to facilitation. A possible explanation to these results could be that the local circuits involved on memory consolidation and recall are different in nature. On this perspective, the amnestic effect of MT3 over memory consolidation should be consequence of GABAergic interneurons inhibition suppression; while the effect on recall, should be over glutamatergic synapses modulation. Thereby, the present work, with the objective to investigate how the M4 receptor modulates long-term synaptic plasticity and interacts with the GABAergic system, in vivo electrophysiological approach of anesthetized rats’ hippocampus was applied. Hence, field excitatory postsynaptic potentials (fEPSP) from CA1 were recorded after stimulation of contralateral Schaffer Collateral pathway with drugs infusion 15 min before or after high or low frequency electric stimulation (HFS: 10 trains 0.5 Hz, 20 pulses 100 Hz; LFS: 600 pulses 1 Hz, respectively). Neither MT3 (4.00 μg/μl), bicuculline (0.06 μg/μl), baclofen (0.20 μg/μl) nor vehicle, isolated or combined, changed the baseline evoked response amplitude 15 min after infusion nor the paired-pulse facilitation ratio (PPF). MT3 apparently attenuated, but not significantly, the long-term potentiation (LTP) compared to control (31.8% and 66.0% potentiation 60 min after HFS, respectively). In addition, there was no significant difference between baseline and 60 min after HFS fEPSP amplitude at MT3 group. Bicuculline, although did not abolish LTP neither changed PPF, it did produce a potentiation of only 36.4%. Baclofen induced a potentiation similar to control group. Baclofen administration also significantly reduced PPF compared to baseline. The simultaneous administration of MT3 and bicuculline or baclofen led to a potentiation similar to the control group. MT3 did not show any effect over LTP maintenance when applied 15 min after HFS. Lastly, it was not possible to induce long-term depression (LTD) with the used LFS protocol. Although there was no statistical significance between groups due to the low animal numbers used, data suggest that bicuculline had reduced LTP amplitude. Baclofen did alter PPF and the same was not observed on control group. When bicuculline or baclofen were injected with MT3, those alterations were not observed. These are inconclusive and preliminary results, notwithstanding this work allowed to set up the in vivo electrophysiology technique in anesthetized animals what will provide new tools for future research.