![]() Public Health RelevanceĪlthough in widespread use for >150 years, how general anesthetics cause loss of consciousness remains one of the great mysteries of biomedical science. ![]() We will use the information from these experiments to aid in seeking electrophysiological correlates of the state transitions manifested in LOC/ROC, and we will derive clinically accessible measures of sensory awareness based on population coding and cortical connectivity using state of the art analysis and modeling techniques. Here we will record synaptic and spiking activity in entire cortical columns in response to microstimulation and auditory and visual sensory stimuli to determine if connectivity changes upon LOC/ROC at thalamo-cortical synapses, as predicted by the TSH, or at cortico-cortical synapses, consistent with the IITC. In the second and third Aims, we will investigate connectivity along the ascending and descending thalamo-cortical pathway. By recording auditory responses in two thalamic areas, MGv and MGd, and their respective hierarchically connected cortical targets, A1 and PAF, we can determine whether anesthetics block information transfer from thalamus to cortex, as predicted by the TSH, or whether even in the face of maintained thalamic input cortical responses become impoverished upon LOC due to observed changes in local network activity caused by anesthetics, consistent with the IITC. In the first Aim, we will focus on how much information responses of cells in auditory cortex carry about sensory stimuli, both at the single cell level an at the population level, and how this information changes upon loss and recovery of consciousness (LOC/ROC). The absence of sensory awareness is a manifestation of LOC that reflects degraded information transfer between the periphery and high order cortex, but where and how this breakdown occurs is unclear. A practical benefit to public health will be assays of consciousness based on population codes and cortical connectivity derived from cortical surface recordings, which are readily obtained in clinical settings. We will test these competing hypotheses by recording unit activity and local field potentials (LFPs) in rats chronically implanted with multisite electrodes in auditory thalamus and auditory and visual cortex. those just causing LOC), which prevent incorporation of sensory information into cortical hierarchical processing. ![]() We postulate that propofol, isoflurane and dexmedetomidine, acting at diverse molecular loci, share a common cortical mechanism for producing LOC: degradation of stimulus representation and suppression of cortico-cortical connectivity at just-hypnotic doses (i.e. The latter proposes that anesthetics act across wide areas of cortex to reduce the repertoire of network states (information) and connectivity (integration). In the former, disruption of thalamo-cortical information transfer is thought critical for LOC. In this proposal, we will test two competing hypotheses, the thalamic switch hypothesis (TSH) and the information integration theory of consciousness (IITC). Rumble Resources Limited was incorporated in 2011 and is headquartered in West Perth, Australia.Elucidating the mechanism by which anesthetics cause loss of consciousness (LOC) will benefit patient care and provide insight into the neural basis of consciousness. The company also holds 100% interests in the Warroo project comprising three exploration license applications covering 1082 square kilometers, and the Lamil project located in the East Pilbara region of Western Australia and an interest in the Braeside-Barramine project covering an area of approximately 673 square kilometers located in the East Pilbara region of Western Australia. ![]() It holds 100% interest in the Western Queen project comprising two mining leases and 2 exploration tenements located in Mt Magnet, Western Australia 80% interest the Munarra Gully project located in Cue District, Murchison and 75% interest in the Earaheedy project located to the north of Wiluna, Western Australia. The company explores for zinc, lead, copper, silver, vanadium, gold, and nickel deposits, as well as platinum-group metals. ![]() Rumble Resources Limited engages in the acquisition, exploration, and evaluation of base and precious metal projects in Australia. ![]()
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