Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1)-a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence-a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations-and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that although basic adaptation to redundant stimuli was present early (50 ms) in layer 4 responses, DD emerged later (150-230 ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7 Hz) and high-gamma (70-80 Hz) oscillations in L2/3 and decreased beta oscillations (26-36 Hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, whereas "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

Spatiotemporal dynamics across visual cortical laminae support a predictive coding framework for interpreting mismatch responses.

Context modulates neocortical processing of sensory data. Unexpected visual stimuli elicit large responses in primary visual cortex (V1) -- a phenomenon known as deviance detection (DD) at the neural level, or "mismatch negativity" (MMN) when measured with EEG. It remains unclear how visual DD/MMN signals emerge across cortical layers, in temporal relation to the onset of deviant stimuli, and with respect to brain oscillations. Here we employed a visual "oddball" sequence - a classic paradigm for studying aberrant DD/MMN in neuropsychiatric populations - and recorded local field potentials in V1 of awake mice with 16-channel multielectrode arrays. Multiunit activity and current source density profiles showed that while basic adaptation to redundant stimuli was present early (50ms) in layer 4 responses, DD emerged later (150-230ms) in supragranular layers (L2/3). This DD signal coincided with increased delta/theta (2-7Hz) and high-gamma (70-80Hz) oscillations in L2/3 and decreased beta oscillations (26-36hz) in L1. These results clarify the neocortical dynamics elicited during an oddball paradigm at a microcircuit level. They are consistent with a predictive coding framework, which posits that predictive suppression is present in cortical feed-back circuits, which synapse in L1, while "prediction errors" engage cortical feed-forward processing streams, which emanate from L2/3.

Genotypic analyses and antimicrobial resistance profiles of Campylobacter jejuni from crows (Corvidae) of United States and India reflect their respective local antibiotic burdens.

AIM: The study examined the hypothesis that crow-borne Campylobacter can function as environmental reservoirs and indicators of antibiotic resistance (AR) determinants circulating in a human population. METHODS AND RESULTS: Two species of crows from Washington (WA), United States, and Kolkata, India, respectively, were examined for their ability to carry antibiotic resistant Campylobacter. Campylobacter jejuni was the only species isolated by selective agar plating from crow faecal samples. Disk diffusion method used to compare the AR profile of the isolates showed tetracycline (TET) resistance to be the most prevalent (27%) among WA isolates, followed by ciprofloxacin (CIP; 24%). Among Kolkata isolates, nalidixic acid resistance was most common (36%), followed by CIP (27%). The AR profile demonstrated by crow isolates of WA reflects those reported by the US National Antimicrobial Resistance Monitoring System for human isolates (2007-2011), where resistance to TET was most prevalent (≈45%), followed by quinolones (≈24%). The Kolkata crow isolates reflected the AR profile of human clinical isolates from India, where 97% resistance was shown to quinolones, followed by TET (18%). Multilocus sequence typing of 37 isolates, including 11 water isolates from the crow roost area, showed 24 different sequence types (STs). Seventeen of these were previously found in wild birds, 2 in human diarrhoea, 4 in poultry and 8 in environmental water. One isolate was found in both water and faeces, though from different sites within WA. CONCLUSIONS: The results indicate that crows most likely acquire the AR from anthropogenic sources. Although they are colonized by specific STs, rarely isolated from humans, they can facilitate the spread of AR. SIGNIFICANCE AND IMPACT OF THE STUDY: By studying two areas in different continents, this research demonstrates that Campylobacter borne by crows can function as environmental reservoirs and indicators of AR determinants that circulate in a human population. This information will be of importance to scientists from the medical and poultry industries.

Increased immunosuppression, not anticoagulation, extends cardiac xenograft survival.

BACKGROUND: Cardiac xenograft function is lost due to delayed xenograft rejection (DXR) characterized by microvascular thrombosis and myocardial necrosis. The cause of DXR is unknown but may result from thrombosis induced by antibody-mediated activation of endothelial cells and/or by incompatibilities in thromboregulatory interactions. METHODS: To examine these issues, a series (Groups 1-6) of previous transgenic CD46 pig-to-baboon heterotopic cardiac transplants were reanalyzed for baseline immunosuppressive levels, graft survival and infectious complications with and without systemic anticoagulation. Groups 1-4 received low dose tacrolimus and sirolimus maintenance therapy, with splenectomy, anti-CD20 and daily alpha-Gal polymer. Group 1 recipients received no anticoagulation. Groups 2-4 were anticoagulated with aspirin and Plavix, Lovenox, or Coumadin, respectively. Group 5 was treated with Lovenox and high dose tacrolimus and sirolimus maintenance therapy. Group 6 recipients received no postoperative anticoagulation but the same immunosuppression as group 5. RESULTS: Median survival (15-22 days) within groups 1-4 was not significantly different. At rejection all tissues exhibited microvascular thrombosis, coagulative necrosis and similar levels of platelet and fibrin deposition. Groups 5 and 6 median survival (76 days) was significantly increased compared to groups 1-4. There was no significant difference in median survival between Lovenox treated recipients (68 days) and anticoagulant free recipients (96 days). Rejected tissues showed vascular antibody deposition, microvascular thrombosis, and myocyte necrosis. CONCLUSION: Significant prolongation in xenograft survival is achieved by improved immunosuppression. These results suggest that ongoing immune responses remain the major stimulus for DXR.