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

No description available.

The thalamic reticular nucleus (TRN), and especially its caudal, sensory-related, half (cTRN), has been hypothesised for years to be at the very heart of thalamic sensory processing modulation, and attentional processes in particular. Very limited behavioural evidence is available, nonetheless, in support of such a functional attribution. In this thesis we carried out a series of investigations, combining immunocytochemical and lesion techniques with tests of behaviour, in order to examine the potential role of cTRN in attention and identify the attentional processes, if any, that it is more likely to contribute to. In chapter II, we looked at the Fos activation levels within modality-specific sectors of cTRN following attentive behaviours to stimulation of different modalities. We observed a selective activation of the visual sector of cTRN in visually attentive animals but not in tactilely attentive, yet visually stimulated, animals, thus demonstrating an involvement of that area in processes of visual attention. In chapter III we looked at the role of cTRN in cross-modal expressions of divided attention. We found that its removal, through neurotoxic lesioning, did not result in any behavioural costs with regard to the division of attention. Detriments in response accuracy, however, suggested that cTRN may be involved in stimulus processing enhancement operations, unrelated with the division of attention. Finally, in chapters IV and V, we looked at the effects of lesions of the visual sector of cTRN (TRNvis) on the ability to orient attention covertly within visual space. We found that the removal of TRNvis did not affect visual covert orienting behaviour, both when this is triggered by exogenous and endogenous means. Overall our results suggest that even though cTRN appears to be involved in some aspects of attention, it does not represent a necessary structure for the generation and operation of certain other forms of attention.

The primary motor cortex (M1) is a key brain area for the generation and control of motor behaviour. Output from M1 can be driven in part by long-range inputs from a collection of thalamic nuclei termed the motor thalamus (MTh), but how MTh input shapes activity in M1 and forelimb motor behaviour remains largely unresolved. To address this issue, we first defined the 3D anatomical coordinates of mouse forelimb motor thalamus (MThFL) by employing conventional retrograde and virus-based tracing methods targeted to the forelimb region of M1 (M1FL). These complimentary approaches defined MThFL as a ~0.8 mm wide cluster of neurons with anatomical coordinates 1.1 mm caudal, 0.9 mm lateral to bregma and 3.2 mm below the pial surface. Thus, MThFL incorporates defined areas of the ventrolateral, ventral anterior and anteromedial thalamic nuclei. To investigate the importance of M1FL and MThFL during skilled motor behaviour, we developed and optimised a quantitative behavioural paradigm in which head-restrained mice execute forelimb lever pushes in response to an auditory cue to receive a water reward. Forelimb movement trajectories were mapped using high-speed digital imaging and multi-point kinematic analysis. We inactivated both M1FL and MThFL of mice performing this motor behaviour using a pharmacological strategy, which in both cases resulted in a significant reduction in task performance. Inactivating M1FL significantly affected forelimb coordination and dexterity, resulting in erratic motion and posture. In contrast, mice with MThFL inactivated displayed a reduction in total motor output, although correct posture was maintained. We performed extracellular recordings in MThFL of expert-level mice, demonstrating that motor thalamic output during execution of task was dominated by a robust response to the onset of the auditory cue. Cue-evoked responses were also observed in motor thalamic neurons of naive mice. We have developed a novel solution to the stability problem encountered when performing whole-cell patch-clamp recordings from the motor cortex of head-restrained mice performing forelimb motor behaviour, and present preliminary recordings maintained through the execution of forelimb behaviour.

Für das zielgerichtete Verhalten des Menschen ist ein funktionierendes Handlungsüberwachungssystem eine wichtige Voraussetzung. Somit können Fehlhandlungen registriert und verarbeitet werden, um dann anschließend das Verhalten an die entsprechende Situation besser anzupassen. Ein wichtiges neuroanatomisches Korrelat dieses Handlungsüberwachungssystems ist der anteriore Anteil des mittleren cingulären Cortex (anterior midcingulate cortex, aMCC), der in der Funktion der Fehlerverarbeitung eng mit den Basalganglien und dem lateralen präfrontalen Cortex verknüpft ist. In der vorliegenden Arbeit wurde die Bedeutung des Thalamus im Netzwerk der Fehlerverarbeitung genauer untersucht. Es konnte mittels diffusionsgewichteter Traktografie bei 16 gesunden Probanden gezeigt werden, dass speziell der Nucleus ventralis anterior (VA) und der Nucleus ventralis lateralis anterior (VLa) quantitativ stärkere Faserverbindungen mit dem aMCC aufweisen, als die restlichen Thalamuskerne. Desweiteren zeigten 15 Patienten mit Läsionen im Thalamus im Vergleich zur gesunden Kontrollgruppe im Eriksen Flanker Task fehlerspezifische Verhaltensunterschiede. Obwohl die Fehlerrate zwischen diesen Patienten und den Kontrollprobanden nahezu identisch war, konnten die Patienten ihre Fehler als solche signifikant schlechter detektieren und ihr Verhalten nach einem Fehler daher auch schlechter anpassen. Die EEG Daten zeigten für die Patientengruppe eine in der Amplitude signifikant verminderte error-related negativity (ERN – ein ereignis-korreliertes Hirnpotential, ausgelöst durch Fehlhandlungen, z.B. in Flankierreizaufgaben) im Vergleich zur Kontrollgruppe. Bei 6 Patienten mit Läsionen der VA und VLa Kerngruppe war die ERN nahezu komplett erloschen, wohingegen bei den 9 Patienten, deren Läsionen nicht VA und VLa betrafen, die ERN lediglich vermindert war. / Performance monitoring is an essential prerequisite of successful goal-directed behavior. Research of the last two decades implicates the anterior midcingulate cortex (aMCC) in the human medial frontal cortex and frontostriatal basal ganglia circuits in this function. Here, we addressed the function of the thalamus in detecting errors and adjusting behavior accordingly. Using diffusion-based tractography we found that, among the thalamic nuclei, the ventral anterior and ventral lateral anterior nuclei (VA, VLa) have the relatively strongest connectivity with the RCZ. Patients with focal thalamic lesions showed diminished error-related negativity, behavioral error detection, and post-error adjustments. When the lesions specifically affected the thalamic VA/VLa nuclei these effects were significantly pronounced, which was reflected by complete absence of the error-related negativity. These results reveal that the thalamus, particularly its VA/VLa region, is a necessary constituent of the performance-monitoring network, anatomically well connected and functionally closely interacting with the aMCC.

No description available.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

Extensive neural connections between the anterior thalamic nuclei (ATN) and the hippocampal system may explain the overlapping amnesic syndromes associated with diencephalic and medial temporal lobe brain injury. Despite the debilitating nature of the diencephalic amnesia, treatments for this condition are lacking. In rats, lesions to the ATN or hippocampus generally produce similar memory deficits, which further implicate these structures in a single functional memory system. First evidence is presented here that seemingly permanent and robust spatial working memory deficits seen after lesions to the ATN in rats are ameliorated by environmental intervention and pharmacological treatment. Post-operative housing of ATN-lesioned rats for 30 days in enriched environment resulted in marked improvements in performance on the spatial working memory task in the cross-maze irrespective of whether rats were exposed to enrichment immediately after surgery or enrichment was delayed by 40 days post-surgery. Long-term beneficial effects of enrichment were also demonstrated. Behavioural improvements were observed when Cerebrolysin - a neurotrophic compound - was injected intraperitoneally for 30 days post-surgery. The combination of enrichment and Cerebrolysin treatment was more effective in inducing recovery on a delayed memory test in the cross-maze task. The influence of enrichment and Cerebrolysin on the neural changes produced by ATN lesions was examined utilising an immediate early gene marker c-fos. Replicating previous studies, ATN lesions produced marked hypoactivity in the retrosplenial cortex, but this effect was not reversed by either enrichment or Cerebrolysin. Unexpectedly, enrichment produced further hypoactivation in this region. Although lesion-induced deficits in a radial-arm maze spatial discrimination task were not improved by enrichment, a related study in our laboratory showed that spatial reference memory can also be improved by enrichment in ATN rats. The current research provides strong support for potential opportunities for therapeutic intervention in the human domain.

Thesis (M. Sc.)--University of Canterbury, 2007. / Typescript (photocopy). Includes bibliographical references (leaves 52-61). Also available via the World Wide Web.

Thesis (M. Med. Sc.)--University of Hong Kong, 2007.