Please use this identifier to cite or link to this item: http://hdl.handle.net/10397/85814
Title: Corticofugally induced c-fos expression, synchronized oscillation and its propagation in the thalamus
Authors: Guo, Yiping
Degree: Ph.D.
Issue Date: 2008
Abstract: A variety of fast and slow rhythmic brain oscillations have been revealed to occur spontaneously during different behavioral states. Fast rhythms are associated with cognition, and slow rhythms (e.g. spindle, 7-15 Hz; delta, 1-4 Hz; slow oscillation, 0.3-1 Hz) define the slow-wave sleep. However, the precise cellular and synaptic mechanisms underlying these different rhythms remain unclear and much controversial despite intensive investigations in the past two decades. Even little evidence is available in the auditory system. The present study investigated the mechanisms underlying the generation, synchronization and propagation of the spontaneous slow rhythms (< 15 Hz) in the corticothalamic networks within a given modality and across different modalities in animals under anesthesia by using multi-channel extracellular recordings and immunohistochemical method. In an attempt to study the contribution of the corticofugal projection to thalamic neurons in the ascending auditory circuitry by using Fos as an activity marker, we ascertained for the first time, the presence of dense Fos positive neurons in the ventral division (MGv) of medial geniculate body (MGB) after the auditory cortex (AC) was activated by injection of bicuculline methobromide (BIM), a GABAA receptor antagonist. We further investigated the relationship between c-fos expression in the MGB and corticofugal activation, as well as its pathway and related neurotransmitters and receptor-types. The result indicated that c-fos expression in the MGv was triggered by corticofugal projections, specific to the cortitothalamic activation. C-fos expression could be elicited in the MGB with direct injection of glutamate in certain conditions, but never with acetylcholine. Moreover, direct injections of antagonists for all three glutamate receptor types, NMDA, AMPA and metabotropic glutamate receptors into MGB, have a determining effect in eliminating the cortically induced c-fos expression in the MGv. Multiple electrode recordings showed that BIM injection in the AC triggered synchronized oscillatory activities (0.3-3 Hz, mainly in 1-3 Hz) with burst firing patterns recurring sequentially in the AC and MGB. The animals with the thalamic reticular nucleus (TRN) lesioned by kainic acid, showed no difference in the slow synchronized oscillation in both the thalamus and the neocortex, when compared to that of the un-lesioned animals. Cortically induced c-fos expression in the MGv was not affected by the TRN lesion, either. These results indicated that the corticothalamic synchronized oscillation evoked by cortical hyperactivity was not mediated by a pathway involving the TRN. The results would probably provide us more thought about the traditional notion that all the thalamic oscillations are associated with the hyperpolarizations derived from TRN. We examined MGv neurons under three different conditions: repeatedly acoustically-stimulated, directly chemically-evoked and corticofugally evoked. Only animals with cortical activation showed c-fos expression in the MGv, though MGv neurons showed similar firing rate for all three conditions. The present results concluded that c-fos expression in the MGv was not simply associated with firing rate, but with the firing pattern. The synchronized corticothalamic activities with burst firings were proposed to lead c-fos expression in the MGv because of the strong association between them. The bicuculline-induced bursts were different from the spindle LTS bursts. The association between c-fos expression in the principle thalamic nuclei and the synchronized slow oscillations in the corticothalamic network was also envisioned in other sensory corticothalamic circuitry, e.g. visual and somatosensory systems. We next investigated the propagations of slow rhythms in the corticothalamic networks in vivo within a given modality and across different modalities. Sleep-or anesthesia- related slow rhythms and the bicuculline-induced slow oscillations were considered in the present study. We found that slow oscillations typically propagated along the rostrocaudal direction in the dorsal thalamus when the cortex was activated with BIM injection. The same propagation in the corticothalamic network was also observed from animals under anesthesia without cortical BIM injection. During this process, the activity in cerebral cortex is always preceding that of the thalamic sites, at least within the same modality. The slow oscillations can be of global distributions, showing nearly-simultaneous EEG or burst discharges in the bilateral hemispheres, or more local events of modality-dependence, recurring independently in different modality systems. However, this modality-specific asynchrony is seldom observed among the TRN sites of different modalities, indicating strong intranuclear connections within the TRN. The results would propose that common principles probably governed the spatiotemporal patterns of different oscillation types. In summary, the present study revealed that c-fos expression in the MGB could be triggered by corticofugal activation. Cortically induced c-fos expression in the MGB was not mediated by the pathway via the TRN. C-fos expression in MGv was not simply associated with the firing rate, but the firing pattern. Burst-firings of possibly high-threshold calcium spikes that were synchronized with the cortical oscillation are proposed to lead c-fos expression in the MGB. Slow oscillations in the corticothalamic network typically propagated along the rostrocaudal direction in the dorsal thalamus. The common principles probably governed the spatiotemporal patterns of different oscillation types. All in all, experimental evidence provided by the present study would further our understanding on the generation and propagation of synchronized excitability within the corticothalamic network of specific modality and across modalities.
Subjects: Hong Kong Polytechnic University -- Dissertations.
Neurophysiology.
Brain -- Physiology.
Cerebral cortex.
Thalamus.
Pages: ix, 162 leaves : ill. ; 31 cm.
Appears in Collections:Thesis

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