Cellular thalamic correlates of the slow (< 1hz) sleep rhythm

Sleep and wakefulness form an inherent, biological rhythm that defines our daily lives. Despite the fact that sleep is a constant interruption to the waking state, its purpose and the neural processes occurring during this behavioural state are not fully understood. However, it is now well established that sleep is not a period of the brain 'silence'. During the transition form light to deep sleep, the activity of the corticothalamic network becomes globally synchronised into consistent, characteristic rhythmic activities at <1Hz, quite in contrast to the so-called cortical 'desynchronisation' characterising states of brain alertness. The mechanism by which global synchronisation in the corticothalamic network arises is not fully defined and previous investigation has focused principally on the role of the cortex. However a clear understanding of the activities of thalamic, as well as cortical, neurones during sleep will aid our understanding into how, and why, global synchronisation occurs, and perhaps why sleep is so fundamental to life. In this thesis, I demonstrate a number of novel activities in two types of thalamic neurones recorded in vitro. Firstly, in thalamocortical neurones, the principal cell type and thalamic output neurones, I demonstrate the presence of an mGluRIa dependent slow (<1Hz) oscillation with identical properties to that seen in the intact brain during sleep. Thalamocortical neurones in relay nuclei subserving visual, somatosensory, auditory and motor systems displayed the slow (<1Hz) oscillation suggesting it could be the substrate for global thalamic synchronization at <1Hz. In addition, I provide a full characterisation of the cellular mechanism of this <1Hz oscillatory activity and demonstrate that during mGluRIa activation, the window component of the low-voltage activated Ca2+ current is unmasked, due to a reduction in the constitutive K+ leak current, inducing bistability-mediated activities that underlies the generation of the slow (<1Hz) oscillation. In neurones of the nucleus reticularis thalami, overlying the thalamus and providing an inhibitory drive to thalamocortical neurones, I also demonstrate a slow (<1Hz) oscillation, again with identical properties as seen in this cell type in the intact brain during sleep. I demonstrate that this slow (<1Hz) oscillation is dependent on mGluRIa activation and provide evidence suggesting that it is generated by a bistability-mediated mechanism as occurs in thalamocortical neurones. In light of these findings, I suggests that the thalamus, has a significant role in aiding, as well as maintaining, the global synchronisation of the corticothalamic network at <1Hz during the transition to, and during sleep. The ability of thalamic neurones to generate rhythmic activities at <1Hz due to cortical mGluRIa activation, that results simply in a reduction of the K+ leak current, will provide a strong excitatory drive to organise cortical activity at <1 Hz. A further novel observation was the presence of spikelets and burstlets (compounds of spikelets) in thalamocortical neurones. Investigations into the origin of these events indicated that they were electrophysiological manifestations of interneuronal electrotonic coupling. Furthermore, spikelets and burstlets had the ability to entrain the output of the neurones in which they were observed. Therefore, the presence of electrotonic coupling in thalamic neurones may have a hitherto unrealised role in the synchronization of thalamic activity during both sleep and awake states.