The hippocampal-medial prefrontal circuit has been shown to serve a critical role in decision making and goal directed actions. While the hippocampus (HF) exerts a direct influence on the medial prefrontal cortex (mPFC), there are no direct return projections from the mPFC to the HF. The nucleus reuniens (RE) of the midline thalamus is strongly reciprocally connected with the HF and mPFC and represents the major link between these structures. We investigated the role of RE in functions associated with the hippocampus and the mPFC -- or their interactions. Using two different inactivation techniques (pharmacological and chemogenetic), we sought to further define the role of RE in spatial working memory (SWM) and behavioral flexibility using a modified delayed non-match to sample (DNMS) working memory task. We found that the reversible inactivation of RE with muscimol critically impaired SWM performance, abolished well-established spatial strategies and produced a profound inability to correct non-rewarded, incorrect choices on the T-maze (perseverative responding). We observed similar impairments in SWM following the chemogenetic (DREADDs) inactivation of RE or selective RE projections to the ventral HF. In addition, we showed that the inhibition of RE terminals to the dorsal or ventral HF altered task related behaviors by increasing or decreasing the time to initiate the task or reach the reward, respectively. Finally, we examined discharge properties of RE cells across sleep-wake states in behaving rats. We found that the majority of RE cells discharge at high rates of activity in waking and REM and at significantly reduced rates in SWS, with a subpopulation firing rhythmically in bursts during SWS. We identified five distinct subtypes of RE cells that discharged differently across vigilant states; those firing at highest rates in waking (W1, W2), in REM sleep (R1, R2) and SWS (S1). Given the differential patterns of activity of these cells, we proposed they may serve distinct functions in waking – and possibly in SWS/REM sleep. In sum, our findings indicate that RE is critically involved in mnemonic and executive functions and the heterogeneous activity of these cells support a role for RE in arousal/attention, spatial working memory and cognition. / Includes bibliography. / Dissertation (Ph.D.)--Florida Atlantic University, 2018. / FAU Electronic Theses and Dissertations Collection

The ability to selectively attend to aspects of the environment which signal opportunity or danger, while marginalising irrelevant stimuli is critical to an animal's survival. With finite cognitive resources, the brain must dedicate resources to only those stimuli that are biologically significant. Incoming thalamic information must therefore be filtered. The thalamic reticular nucleus has long been considered critically involved in modulating thalamic sensory processing. Sharing connections with both the thalamus and cortex, it is ideally located to modulate the transfer of pertinent incoming sensory information. This thesis sought to determine the functional role of the thalamic reticular nucleus in attentional processes by combining lesion techniques and well established behavioural paradigms. Chapter 3 examined the role of visual thalamic reticular nucleus lesions on performance in a two-alternative forced choice reaction time task when auditory distractors were presented. No effect of the lesion was found. Chapter 4 examined excitotoxic lesions of thalamic retlcular nucleus on performance in the 7-stage attentional set shifting task. No effect of lesion on performance was found. Chapter 5 examined mediodorsal thalamus and rostral thalamic reticular nucleus lesions on performance in the attentional set shifting task. Despite strong connectivity with prefrontal regions known to be involved in this task, there was no effect of either lesion. Finally, chapter 6 examined the effects of reducing dopamine input into the thalamic reticular nucleus on a two alternative forced choice reaction time task. Following bilateral lesions the animals were impaired in the re-orientation of attention – suggesting a critical role for both the thalamic reticular nucleus and dopamine in attentional processes. Taken together, these results suggest that while the thalamic reticular nucleus is involved in attention, it is not involved in every aspect.

Functional magnetic resonance imaging (fMRI) has been widely used to study cortical and subcortical mechanisms related to pain. The pathophysiology of burning mouth disorder (BMD) is not clearly understood. Central neuropathic mechanisms are thought to be main players in BMD. This study aimed to compare the location and extension of brain activation following thermal stimulation of the trigeminal nerve with fMRI blood oxygenation level dependent (BOLD) signal. This study included 8 female patients with BMD and 8 matched pain-free volunteers. Qualitative and quantitative differences in brain activation patterns between the two study groups were demonstrated. There were differences in the activation maps regarding the location of activation, with patients displaying greater BOLD signal changes in the right anterior cingulate cortex (ACC BA 32/24) and bilateral precuneus (pandlt;0.005). The control group showed larger BOLD signal changes in the bilateral thalamus, right middle frontal gyrus, right pre-central gyrus, left lingual gyrus and cerebellum (pandlt;0.005). It was also demonstrated that patients had far less volumetric activation throughout the entire brain compared to the control group. These data are discussed in light of recent findings suggesting brain hypofunction as a key player in chronic neuropathic pain conditions.

Le thalamus, via les neurones glutamatergiques thalamocorticaux (TC), est le dernier relai dans le cheminement des informations de la périphérie vers le cortex. Le réseau intrathalamique repose sur les interactions entre ces neurones TC et des neurones GABAergiques regroupés dans le Noyau Réticulé Thalamique (NRT). Ces deux types de neurones contribuent au traitement des informations issues de la périphérie et à la genèse des activités oscillantes pendant le sommeil. Pendant les phases de sommeil à ondes lentes les neurones TC et NRT émettent de manière périodique et synchrone des bouffées de potentiels d'action à haute fréquence associées à de forts influx de calcium dus à l'activation des canaux calciques de type T. Au cours de ma thèse, j'ai cherché à déterminer si ces activités étaient susceptibles de modifier la force synaptique. En utilisant un protocole d'induction mimant l'excitabilité des neurones thalamiques durant le sommeil à ondes lentes, j'ai mis en évidence une dépression à long terme (LTD) de la synapse GABAergique entre les neurones NRT et TC. J'ai montré que cette LTD était d'origine post-synaptique et nécessitait en synergie 1) l'activation des récepteurs GABAA présents à la synapse, 2) une forte entrée de calcium dans les neurones TC spécifiquement par les canaux calciques de type T, 3) l'activation des récepteurs métabotropiques du glutamate. L'exigence d'une entrée massive de calcium par les canaux calciques de type T suggère que seules les activités thalamocorticales associées au sommeil à ondes lentes sont susceptibles de déclencher cette LTD. / Thalamocortical (TC) glutamatergic neurons from the thalamus are the last relay in the flow of information from the periphery to the cortex. Intrathalamic network is based on the interactions between these TC neurons and the GABAergic neurons located in the Thalamic Reticularis Nucleus (TRN). These two types of neurons contribute to the processing of information arising from the periphery and to the generation of oscillatory activities during sleep. During slow-waves-sleep, NRT and TC neurons discharge rhythmically and synchronously high frequency bursts of action potentials associated with calcium influx occurring through T-type calcium channels. During my thesis, I sought to determine whether these activities were capable of changing synaptic strength. Using an induction protocol mimicking the excitability of thalamic neurons during slow-wave sleep, I highlighted a long-term depression (LTD) of the synapse between NRT GABAergic neurons and TC neurons. I showed that LTD induction had a postsynaptic origin and required synergistically 1) the synaptic activation of GABAA receptors, 2) a high calcium entry in TC neurons specifically through T-type calcium channels 3) the activation of metabotropic glutamate receptors. The requirement of calcium influx through the T-type calcium channels suggests that only thalamocortical activities associated with slow wave sleep may trigger this LTD.

Following a cortical injury, neurons in areas near and connected to the site of injury begin to degenerate. The observed neuronal death may contribute to the severity of the observed behavioral impairments. The purpose of the present study was to examine if progesterone, a hormone known for its effectiveness at reducing cerebral edema, could protect against secondary neuronal death and facilitate the acquisition of an avoidance learning task in an ablation model of cortical injury. Rats served as sham controls or received bilateral ablation of the medial prefrontal cortex followed by a 10-day regimen of progesterone (4 mg/kg) or oil vehicle (1 ml/kg) beginning 1 h after cortical lesions. Progesterone-treated lesion rats showed a significant facilitation of avoidance learning compared to oil- treated lesion controls. In addition, progesterone-treated lesion animals did not differ from either progesterone- or oil-treated sham controls in avoidance learning. Anatomical analysis revealed that progesterone treatment decreased the amount of neuronal death seen in the striatum and the mediodorsal nucleus of the thalamus. The findings are consistent with the notion that progesterone is an effective neuroprotective agent and suggest that the hormone can reduce the behavioral impairments associated with frontal cortical ablation injury.

No description available.

A estimulação epidural do córtex motor (ECM) é eficaz no tratamento da dor neuropática refratária, porém seus mecanismos de ação ainda são incertos. Sabendo que a ECM ativa a via analgésica descendente em ratos, fomos investigar o efeito da ECM sobre os núcleos serotonérgicos descendentes, dorsal da rafe (NDR) e magno da rafe (NMR) e sobre os neurônios da coluna posterior da medula espinhal (CPME). Ratos Wistar, submetidos à ECM, foram avaliados no teste de pressão da pata e seus tecidos foram avaliados frente à imunorreatividade (IR) para Egr-1 (marcador de ativação neuronal), serotonina (5HT) e substância P (SP). A ECM induziu antinocicepção em 62% nos animais, não alterou a ativação do NDR, entretanto ativou o NMR (67%), quando comparado com ratos não estimulados. A ECM aumentou a IR-5HT em 75% no NDR e em 92% no NMR. Na CPME, a ECM inibiu os neurônios nociceptivos (48%), porém não interferiu com a IR-SP. Estes resultados sugerem que a ECM induz analgesia, em parte, via ativação do sistema serotonérgico descendente. / Motor cortex stimulation (MCS) is effective in the treatment of refractory neuropathic pain; however, its mechanisms of action remain unclear. Since the MCS activates the descending pain pathway in rats, we investigated the MCS effect on the descending serotonergic nuclei, dorsal raphe nucleus (DRN) and the magnus raphe nucleus (MRN) and also on the neurons of the dorsal horn of the spinal cord (DHSC). Wistar rats, submitted to MCS, were evaluated by paw pressure test and its tissues were evaluated by immunoreactivity (IR) to Egr-1 (neuronal activation marker), serotonin (5HT) and substance P (SP). MCS induced antinociception by 62% in animals, although did not modify the NDR activation; however, activated the MRN (67%), when compared to control groups. MCS increased the IR-5HT by 75% in the NDR and 92% in the MRN. In the DHSC, MCS inhibited the nociceptive neurons (48%), however did not change the IR-SP. These results suggest that MCS induce antinociception, partly, by the descending serotonergic pathway activation.

Les noyaux Reuniens et Rhomboïde (ReRh) du thalamus, par leurs connexions denses et réciproques avec l’hippocampe (HP) et le cortex préfrontal médian (CPFm), constituent un relais clé entre ces deux structures et semblent impliqués dans les interactions HP-CPFm, support de la persistance des souvenirs. Par des approches de lésion, d’inactivation pharmacogénétique et d’imagerie cellulaire appliquées à différents paradigmes comportementaux, l’implication des noyaux ReRh dans les processus mnésiques, particulièrement de consolidation, a été évaluée. Nos travaux ont notamment mis en évidence que les noyaux ReRh, par leur implication spécifique dans les processus offline de consolidation, sont nécessaires pour la persistance à long terme d’un souvenir de peur conditionnée au contexte chez le rat. Ainsi l’implication du noyau Reuniens dans les processus de consolidation, initialement mise en évidence dans le cas de la mémoire spatiale, peut être étendue à d’autres types de mémoire HP-dépendants. / Neuroanatomical and electrophysiological data place the thalamic Reuniens and Rhomboid nuclei as a key relay between the hippocampus (HP) and the medial prefrontal cortex (mPFC), two brain structures essential for memory. As such, the ReRh nuclei are thought to be involved in HP-mPFC interactions, supporting consolidation processes, and thus memory persistence. Using excitotoxic lesion, chemogenetic inactivation and cellular imaging approaches in various behavioral paradigms, we assessed the implication of the ReRh nuclei in memory processes, particularly consolidation. Our results show that the ReRh nuclei are necessary for offline consolidation of contextual fear memory in rats. A similar conclusion has been drawn from a previous study taxing spatial memory, another HP-dependent type of memory. Thus, the present data show that the necessity of the ventral midline thalamus to systems-level consolidation is not limited to a particular type of memory but could be more general.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The purposes of this study were to perform retrospective studies about epilepsy and idiopathic epilepsy in dogs presented at the Veterinary Neurology Service, University Veterinary Hospital, of Federal University of Santa Maria and use a flexible urethral catheter as an alternative method to measuring intracranial pressure in rabbits with head injury and compare the data with ventriculostomy catheter (conventional method) . In the first paper, 66 records of dogs with presumptive diagnosis of epilepsy were selected. 66.7% of them, were epilepsy idiopatic, 21.2% symptomatic and 12.1% probably symptomatic. The mongrel dogs were the most affected and age-group prevailed was one to 5-year-old. The tonic-clonic seizure was the most observed, the main pre-ictal symptom was to try to catch owner´s attention and compulsive walking in the post-ictal period. In the second paper, 21 dogs with idiopatic epilepsy were included; the median age at onset of seizures was 3.4 years, the median number of seizure before the start of treatment was 25.7 and duration of seizure before treatment was 71 days. The phenobarbital was used as monotherapy with dose from 1.4 to 12 mg kg-1 and the median of serum concentration was 26.41 μg kg-1. There was significant reduction in the frequency of the seizure after start the treatment. 19% of dogs were in remission of seizure. In blood analysis, there was increased serum activities of AP (23,81%) and ALT (14,20%), decreased total protein (42,29%), hypoalbuminemia (9,5%) and it was not increased AST activities. The main secondary lesions were liver disease and hypothyroidism. In the third paper, New Zealand rabbits were randomly distributed into two groups, G1: measuring the ICP with ventriculostomy catheter (n=6) and G2: measuring the ICP with urethral catheter (n=6). Two craniotomy were performed in the right and left parietal region for the implantation of the ventriculostomy catheter and/or flexible urethral catheter and epidural 4F Fogarty arterial embolectomy catheter, respectively. MAP, CPP, HR, RF and RT values were measured before and after craniotomy. The ICP value was mensured after craniotomy, ever five minutes during 40 minutes after the balloon was inflated with 0.3 ml of NaCl 0.9% and more 40 minutes after the balloon was inflated with 0.6 ml. The ICP value increased in both groups, however, the ICP values were lower in the rabbits measured with flexible urethral catheter. The flexible urethral catheter can be used as alternative method to measure ICP values im rabbits with head injury. / Os objetivos deste estudo foram: realizar um estudo retrospectivo sobre epilepsia em cães e outro com epilepsia idiopática atendidos no Serviço de Neurologia Veterinária, do Hospital Veterinário Universitário (HVU) da Universidade Federal de Santa Maria e utilizar a sonda uretral flexível como método alternativo para aferição da pressão intracraniana em coelhos com trauma cranioencefálico induzido pelo cateter de Fogarty 4 Fr (balão epidural) e comparar os dados obtidos com o método convencional de cateter de ventriculostomia. No primeiro artigo, foram selecionados os registros de 66 cães com diagnóstico presuntivo de epilepsia, sendo que 66,7% apresentaram epilepsia primária, 21,2% com sinais clínicos e em 12,1% com prováveis sinais clínicos. Os cães sem raça definida foram os mais acometidos e a faixa etária predominou entre um e cinco anos de idade. A crise epiléptica generalizada tônico-clônica foi a mais observada, a ocorrência maior das crises foram durante a noite; os sinais mais observados foram: a procura pelo tutor no período pré-ictal e o andar compulsivo no período pós-ictal. No segundo artigo, foram incluídos 21 cães com epilepsia idiopática, com média de idade para o início das crises epilépticas de 3,4 anos, apresentando em média 25,7 crises epilépticas antes do início do tratamento e o diagnóstico presuntivo foi determinado em média 71 dias após a primeira crise. Foi utilizada a monoterapia com fenobarbital na maioria dos cães e dose variou entre 1,4 a 12 mg kg-1 e a concentração sérica teve média de 26,41 μg ml-1. Após o início do tratamento houve uma redução significativa das crises epilépticas. 19% dos cães apresentaram remissão das crises epilépticas. Nos exames hematológicos, foi observado aumento da FA em 23,81% e da ALT em 14,29%, diminuição da proteína total em 42,86%, hipoalbuminemia em 9,5% dos cães e não foi observado aumento nos níveis da AST. As principais lesões secundárias observadas foram lesão hepática e hipotireiodismo. No terceiro estudo, coelhos da raça Nova Zelândia foram distribuídos aleatoriamente em dois grupos, denominados G1: mensuração da PIC com cateter de ventriculostomia (n=6) e G2: mensuração com sonda uretral (n=6). Foram realizadas duas craniotomias nas regiões parietal direita e esquerda para a implantação do cateter de ventriculostomia ou da sonda uretral flexível e o balão epidural, respectivamente. Foram mensuradas a PAM, PPC, FC, FR e a TR antes e após a craniotomia. A PIC foi avaliada após a craniotomia e a cada cinco minutos depois do preenchimento do balonete com 0,3 ml de NaCl 0,9% permanecendo por 40 minutos e, com 0,6 ml pelo mesmo período de tempo. A PIC aumentou em ambos os grupos, sendo menores os valores registrados com a sonda uretral flexível. Embora haja a necessidade de outros estudos, a sonda uretral flexível demonstrou ser um método alternativo de mensuração da PIC em coelhos com trauma cranioencefálico.

A estimulação epidural do córtex motor (ECM) é eficaz no tratamento da dor neuropática refratária, porém seus mecanismos de ação ainda são incertos. Sabendo que a ECM ativa a via analgésica descendente em ratos, fomos investigar o efeito da ECM sobre os núcleos serotonérgicos descendentes, dorsal da rafe (NDR) e magno da rafe (NMR) e sobre os neurônios da coluna posterior da medula espinhal (CPME). Ratos Wistar, submetidos à ECM, foram avaliados no teste de pressão da pata e seus tecidos foram avaliados frente à imunorreatividade (IR) para Egr-1 (marcador de ativação neuronal), serotonina (5HT) e substância P (SP). A ECM induziu antinocicepção em 62% nos animais, não alterou a ativação do NDR, entretanto ativou o NMR (67%), quando comparado com ratos não estimulados. A ECM aumentou a IR-5HT em 75% no NDR e em 92% no NMR. Na CPME, a ECM inibiu os neurônios nociceptivos (48%), porém não interferiu com a IR-SP. Estes resultados sugerem que a ECM induz analgesia, em parte, via ativação do sistema serotonérgico descendente. / Motor cortex stimulation (MCS) is effective in the treatment of refractory neuropathic pain; however, its mechanisms of action remain unclear. Since the MCS activates the descending pain pathway in rats, we investigated the MCS effect on the descending serotonergic nuclei, dorsal raphe nucleus (DRN) and the magnus raphe nucleus (MRN) and also on the neurons of the dorsal horn of the spinal cord (DHSC). Wistar rats, submitted to MCS, were evaluated by paw pressure test and its tissues were evaluated by immunoreactivity (IR) to Egr-1 (neuronal activation marker), serotonin (5HT) and substance P (SP). MCS induced antinociception by 62% in animals, although did not modify the NDR activation; however, activated the MRN (67%), when compared to control groups. MCS increased the IR-5HT by 75% in the NDR and 92% in the MRN. In the DHSC, MCS inhibited the nociceptive neurons (48%), however did not change the IR-SP. These results suggest that MCS induce antinociception, partly, by the descending serotonergic pathway activation.