Thesis (Ph. D.)--University of Washington, 1997. / Vita. Includes bibliographical references (leaves [58]-64).

Many neurones in the thalamus, like neurones in other parts of the CNS are excited by iontophoretlcally applied acetylcholine (ACh), and it has been suggested that ACh may be involved in synaptic transmission in the thalamus. In these experiments, the iontophoretlc technique was employed to investigate the location, and the neurophysiological and pharmacological properties of neurones in the ventrolateral nucleus of the thalamus (VL), which responded to electrical stimulation of the ipsilateral nucleus of the posterior commisure (NPC). Stimulation of the contralateral brachium conjunetivum (BC) was used to confirm the presence of the recording micropipette in VL. Four drugs were applied in various sequences to most neurones encountered above, in and below VL. DL-homocysteate (DLH) was used for the activation and localisation of quiescent neurones; ACh was applied to test whether the neurones were cholinoceptivej eserine (physostigmine) was used as an anticholinesterase; and atropine was used as a muscarinic blocking agent. Choiinoceptive cells were found above (3.0-6.0 mm below the fornix), and In VL (0.0-10.0mm below the fornix), the highest proportion being located in VL. The majority of cholinoceptive cells in VL responded to NPC and to BC stimulation. Cholinoceptive neurones located above VL were not evoked either by NPC or BC stimulation, while those in the lowest part of VL were evoked by NPC stimulation only. Although atropine blocked the effect of iontophoretically applied ACh, It did not affect synaptic responses evoked by stimulation of NPC and/or BC fibers. Eserine excited some cells and potentiated the actions of ACh. These results indicate that a pathway arising from the NPC projects to the ipsilateral VL and that this fiber tract is non-cholinergic. / Medicine, Faculty of / Cellular and Physiological Sciences, Department of / Graduate

Sparse thalamocortical cell population synchronicity during sleep spindle oscillations has been hypothesized to promote the integration of hippocampal memory information into associated neocortical representations 1. We asked the question of whether sparse or rhythmic activity in thalamocortical cells of the reuniens nucleus influence memory consolidation and cognitive flexibility during learning after sleep. For this study, I designed a novel attentional set-shifting task and incorporated optogenetics with closed-loop stimulation in sleeping rats to investigate the effects of sparse (nonrhythmic) or rhythmic spindle-like (~10Hz) activity in thalamic cells of the reuniens nucleus on learning and cognitive flexibility. We show that, as predicted, post-sleep setshifting performance improved after sleep with non-rhythmic optogenetic stimulation in the thalamic nucleus reuniens relative to rhythmic optogenetic stimulation. While both non-rhythmic and rhythmic optogenetic stimulation led to an increase in perseverative errors, only non-rhythmic optogenetic stimulation showed effects of learning from errors, which correlated with sleep, and which ultimately had a net benefit in set-shifting performance compared to rhythmic optogenetic stimulation and the control group. / Includes bibliography. / Thesis (M.A.)--Florida Atlantic University, 2020. / FAU Electronic Theses and Dissertations Collection

Fast, automated segmentation of the thalamic nuclei in the brain has long been desired as it provides for direct visualization of the target for certain procedures like Deep Brain Stimulation (DBS) that target a specific nucleus. It is also beneficial in the study of other pathologies that pertain to different nuclei. In this thesis, a novel approach to fast automated segmentation of thalamic nuclei called Shortened Template and THalamus for Optimal Multi Atlas Segmentation (ST THOMAS) was developed using the multi-atlas segmentation approach. It was designed with a focus on robustness and speed by making use of an averaged template for registration and cropping the inputs and the template. The performance of ST THOMAS was first evaluated on 7T MRI data by comparing with manual delineation (ground truth) by an expert neuroradiologist. Dice coefficients and Volumetric Similarity Indices were used as metrics. To extend the applicability of this method, 3T MRI data were also evaluated. Finally, applications to real time ventralintermideiate (VIM) nucleus targeting for DBS and study of the effects of alcoholism are demonstrated.

Diencephalic amnesia is thought to be the result of damage to a single thalamic structure that is responsible for the memory impairment. However, an alternative view is that different thalamic structures contribute to the memory impairment in subtly different ways. Paired-associate learning is one important measure of learning and memory that is highly sensitive to disruption in people with amnesia or dementia. The current study will investigate the influence of lesions to two thalamic subregions, the anterior thalamic nuclei (AT) and the lateral thalamic nuclei (LT) in an object-odour paired associate learning task. Each of these subregions has been suggested by the literature as critical for amnesia after thalamus injury. The current study does not involve a place/ space component. Both AT and LT lesions caused impairments in the object-odour paired associate task, but not in the simple discrimination tasks. The results of this study provide new evidence to suggest that the anterior thalamic region may be responsible for more than spatial memory processing. This result is inconsistent with those of Aggleton & Brown (1999) that consider the AT to be part of an 'extended hippocampal system'. The deficits observed from LT lesions in this study provide new insight into the lateral thalamic region's role in pattern processing.

Diencephalic amnesia is thought to be the result of damage to a single thalamic structure that is responsible for the memory impairment. However, an alternative view is that different thalamic structures contribute to the memory impairment in subtly different ways. Paired-associate learning is one important measure of learning and memory that is highly sensitive to disruption in people with amnesia or dementia. The current study will investigate the influence of lesions to two thalamic subregions, the anterior thalamic nuclei (AT) and the lateral thalamic nuclei (LT) in an object-odour paired associate learning task. Each of these subregions has been suggested by the literature as critical for amnesia after thalamus injury. The current study does not involve a place/ space component. Both AT and LT lesions caused impairments in the object-odour paired associate task, but not in the simple discrimination tasks. The results of this study provide new evidence to suggest that the anterior thalamic region may be responsible for more than spatial memory processing. This result is inconsistent with those of Aggleton & Brown (1999) that consider the AT to be part of an 'extended hippocampal system'. The deficits observed from LT lesions in this study provide new insight into the lateral thalamic region's role in pattern processing.

Episodic memory is processed by the extended hippocampal system, and pathology or injury to individual components of this system can result in deficits in spatial learning and memory (Aggleton & Brown, 1999). Extensive research regarding spatial memory has been carried out on the anterior thalamic nuclei, a component of the extended hippocampal system, but the contribution of the laterodorsal thalamic nuclei, an adjacent structure with similar neural connections, is less clear. The purpose of the present study was to compare the effects of selective anterior thalamic nuclei lesions (AT) with selective laterodorsal thalamic nuclei lesions (LD) in a novel land-based spatial reference memory task. This assessed the use of proximal and distal visual cues on the propensity to use allocentric or egocentric navigation strategies to locate a specific place in space, as well as the temporal evolution of these navigation strategies. AT lesion impairments were observed in the acquisition trials in both proximal and distal cue conditions. LD lesion rats were unimpaired in the acquisition trials in both visual cue conditions. Across the probe trials, lesion effects were not observed when tested for general navigation, egocentric or allocentric strategies, and there was no clear improvement in performance over the four weeks of probe trials. However, performance was consistently poorer for all groups when proximal cues facilitated navigation compared to distal cues. Performance differences related to cue proximity may reflect the influence of motion parallax, the perceived displacement rate of visual cues. The absence of lesion effects across probes were thought to be due to the preferential use of cued navigation, which was reliant on a single salient beacon, and the lack of integration between cued and place navigation, which was reliant on the formation of a spatial representation.

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

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.