Differential modifications of synaptic weights during odor rule learning: dynamics of interaction between the piriform cortex with lower and higher brain areas.

Learning of a complex olfactory discrimination (OD) task results in acquisition of rule learning after prolonged training. Previously, we demonstrated enhanced synaptic connectivity between the piriform cortex (PC) and its ascending and descending inputs from the olfactory bulb (OB) and orbitofrontal cortex (OFC) following OD rule learning. Here, using recordings of evoked field postsynaptic potentials in behaving animals, we examined the dynamics by which these synaptic pathways are modified during rule acquisition. We show profound differences in synaptic connectivity modulation between the 2 input sources. During rule acquisition, the ascending synaptic connectivity from the OB to the anterior and posterior PC is simultaneously enhanced. Furthermore, post-training stimulation of the OB enhanced learning rate dramatically. In sharp contrast, the synaptic input in the descending pathway from the OFC was significantly reduced until training completion. Once rule learning was established, the strength of synaptic connectivity in the 2 pathways resumed its pretraining values. We suggest that acquisition of olfactory rule learning requires a transient enhancement of ascending inputs to the PC, synchronized with a parallel decrease in the descending inputs. This combined short-lived modulation enables the PC network to reorganize in a manner that enables it to first acquire and then maintain the rule.

Immunohistological and Ultrastructural Study of the Inflammatory Response to Perforated Polyimide Cortical Implants: Mechanisms Underlying Deterioration of Electrophysiological Recording Quality.

The deterioration of field potential (FP) recording quality and yield by in vivo multielectrode arrays (MEA) within days to weeks of implantation severely limits progress in basic and applied brain research. The prevailing hypothesis is that implantation of MEA platforms initiate and perpetuate inflammatory processes which culminate in the formation of scar tissue (the foreign body response, FBR) around the implant. The FBR leads to progressive degradation of the recording qualities by displacing neurons away from the electrode surfaces, increasing the resistance between neurons (current source) and the sensing pads and by reducing the neurons' excitable membrane properties and functional synaptic connectivity through the release of pro-inflammatory cytokines. Meticulous attempts to causally relate the cellular composition, cell density, and electrical properties of the FBR have failed to unequivocally correlate the deterioration of recording quality with the histological severity of the FBR. Based on confocal and electron microscope analysis of thin sections of polyimide based MEA implants along with the surrounding brain tissue at different points in time after implantation, we propose that abrupt FP amplitude attenuation occurs at the implant/brain-parenchyma junction as a result of high seal resistance insulation formed by adhering microglia to the implant surfaces. In contrast to the prevailing hypothesis, that FP decrease occurs across the encapsulating scar of the implanted MEA, this mechanism potentially explains why no correlations have been found between the dimensions and density of the FBR and the recording quality. Recognizing that the seal resistance formed by adhering-microglia to the implant constitutes a downstream element undermining extracellular FP recordings, suggests that approaches to mitigate the formation of the insulating glial could lead to improved recording quality and yield.