| The textbook view of how the primary, receptive field defining information flows between cortical areas within the brain is that it travels via direct corticocortical afferents. This evidence is based on the large number of fibers in this pathway relative to other pathways that connect one part of cortex to another. Recent evidence suggests, however, that the only pathways that are widely known to convey receptive field input to cortex form few synapses on target neurons relative to other, modulating pathways. Further, a pathway that connects cortical areas to one another, the corticothalamocortical pathway, shares several key properties with these afferents. This suggests that this alternative to the direct corticocortical circuit may be carrying primary information. Receptive field defining input is necessarily strong; by definition receptive field defining pathways must induce similar firing patterns in their target neurons. We thus set out to test the strength of the corticothalamocortical pathway. To do so, however, we first had to further explore the potential of an imaging technique.;Widely utilized in vitro imaging modalities, while advantageous for certain experiments, were not well-suited to the lengthy protocol we sought to use in the investigation of the corticothalamocortical circuit in vitro. Flavoprotein Autofluorescence (FA) imaging offers several advantages over existing techniques, but had not yet been sufficiently vetted for our use. Specifically, it had not yet been shown to be effective over long ranges using glutamate-based stimulation techniques and had not been electrophysiologically verified in vitro. We show in Chapter II that this technique is compatible with such long range glutamate stimulation, has good spatial resolution, is robust, tracks well with cellular activity and primarily reports postsynaptic activation. These properties made it possible for us to demonstrate that this technique can be used to rapidly generate output maps when combined with photostimulation by assessing the previously unexplored topographical relationship between the ventral posterior medial nucleus of the thalamus (VPm) and the thalamic reticular nucleus (TRN) in multiple animals (n = 3). While developing the technique, we became aware of an issue that may be hampering in vitro experiments on human epileptic tissue: variability.;Data collected from human tissue samples are highly variable, often leading to conflicting results both between and within experiments. Our experience with human tissue samples suggests the reason for this may be due to variability in network connectivity. We show in Chapter III that there is high variability in evoked patterns of network activity both across human tissue samples and within a sample cut at different angles. These findings not only support the notion that this variability is present, but also that some of the variability in the literature may be due to the fact that it is very difficult to accurately cut human tissue slices at an angle that is perpendicular to the plane of the overlying pia.;Having sufficiently tested the efficacy of FA imaging for our purposes, we went on to assess the strength of the corticothalamocortical circuit. We show in Chapter IV, using both FA imaging and electrophysiological recordings in an in vitro mouse preparation, that the corticothalamocortical circuit that emanates from the barrel field of primary somatosensory cortex, synapses onto relay cells in the thalamus and then projects to secondary somatosensory cortex is strong. This finding suggests that corticothalamocortical pathways elicit strong activity in their targets, and thus should be viewed as a pathway that may convey, perhaps in tandem with direct corticocortical afferents or perhaps not, the main information being relayed between cortical areas.;Note: 6 supplementary movies are cited in the text and are available online through ProQuest/UMI. These movies are in Windows Media Video (.wmv) format and are numbered Supplementary Movie (1-6) in the text. They correspond, respectively, to data presented in Figures 14, 5, 20, 22, 23 A-C and 23 F. |
