Temporal lobe epilepsy causes severe cognitive deficits, but the circuit mechanisms remain unknown. Interneuron death and reorganization during epileptogenesis may disrupt the synchrony of hippocampal inhibition. To test this, we simultaneously recorded from the CA1 and dentate gyrus in pilocarpine-treated epileptic mice with silicon probes during head-fixed virtual navigation. We found desynchronized interneuron firing between the CA1 and dentate gyrus in epileptic mice. Since hippocampal interneurons control information processing, we tested whether CA1 spatial coding was altered in this desynchronized circuit, using a novel wire-free miniscope. We found that CA1 place cells in epileptic mice were unstable and completely remapped across a week. This spatial instability emerged around 6 weeks after status epilepticus, well after the onset of chronic seizures and interneuron death. Finally, CA1 network modeling showed that desynchronized inputs can impair the precision and stability of CA1 place cells. Together, these results demonstrate that temporally precise intrahippocampal communication is critical for spatial processing. David Geffen School of Medicine Dean's Fund for development of open-source miniaturized microscopes to B.

Temporal lobe epilepsy causes significant cognitive deficits in both human patients and rodent models, yet the specific circuit mechanisms that alter cognitive processes remain unknown. There is dramatic and selective interneuron death and axonal reorganization within the hippocampus of both humans and animal models, but the functional consequences of these changes on information processing at the neuronal population level have not been well characterized. To examine spatial representations of epileptic and control mice, we developed a novel wire-free miniature microscope to allow for unconstrained behavior during in vivo calcium imaging of neuronal activity. We found that epileptic mice running on a linear track had severely impaired spatial processing in CA1 within a single session, as place cells were less precise and less stable, and population coding was impaired. Long-term stability of place cells was also compromised as place cells in epileptic mice were highly unstable across short time intervals and completely remapped across a week. Because of the large-scale reorganization of inhibitory circuits in epilepsy, we hypothesized that degraded spatial representations were caused by dysfunctional inhibition. To test this hypothesis, we examined the temporal dynamics of hippocampal interneurons using silicon probes to simultaneously record from CA1 and dentate gyrus during head-fixed virtual navigation. We found that epileptic mice had a profound reduction in theta coherence between the dentate gyrus and CA1 regions and altered interneuron synchronization. In particular, dentate interneurons of epileptic mice had altered phase preferences to ongoing theta oscillations, which decorrelated inhibitory population firing between CA1 and dentate gyrus. To assess the specific contribution of desynchronization on spatial coding, we built a CA1 network model to simulate hippocampal desynchronization.Critically, we found that desynchronized inputs reduced the information content and stability of CA1 neurons, consistent with the experimental data. Together, these results demonstrate that temporally precise intra-hippocampal communication is critical for forming the spatial code and that desynchronized firing of hippocampal neuronal populations contributes to poor spatial processing in epileptic mice. 3 Main Text:Temporal lobe epilepsy (TLE) is associated with disabling cognitive deficits 1,2 , interneuron cell death 3,4 , and large-scale anatomical reorganization of limbic circuits [5][6][7][8] in both human patients and rodent models. Following cell death, surviving interneurons from both CA1 and dentate gyrus (DG) sprout new local and long-range connections leading to altered timing and kinetics of inhibition 8-12 . These alterations are likely to have dramatic effects on spatial processing as the hippocampus relies on the precise timing of diverse interneuron subtypes that control excitatory inputs [13][14][15][16] . Indeed, initial studies have shown degraded spatial representations in epileptic rodents 17-20 , but i...

Patients undergoing surgery and taking angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) are susceptible to complications related to intraoperative hypotension. Perioperative continuation of such medications in patients undergoing colorectal surgery may be associated with more harm than benefit, as these patients are often exposed to other risk factors which may contribute to intraoperative hypotension. Our objectives were to assess the incidence and severity of postinduction hypotension as well as the rates of acute kidney injury (AKI), 30-day all-cause mortality, 30-day readmission, and hospital length of stay in adult patients undergoing colorectal surgery who take ACEi/ARB.We performed a retrospective chart review of patients undergoing colorectal surgery of ≥4 hour duration at a tertiary care academic medical center between January 2011 and November 2016. The preoperative and intraoperative characteristics as well as postoperative outcomes were compared between patients taking ACEi/ARB and patients not taking these medications.Of the 1020 patients meeting inclusion criteria, 174 (17%) were taking either ACEi or ARB before surgery. Patients taking these medications were more likely to receive both postinduction and intraoperative phenylephrine and ephedrine. The incidences of postoperative AKI (P = .35), 30-day all-cause mortality (P = .36), 30-day hospital readmission (P = .45), and hospital length of stay (P = .25), were not significantly different between the 2 groups.Our results support the current recommendation that ACEi/ARB use is probably safe within the colorectal surgery population during the perioperative period. Intraoperative hypotension should be expected and treated with vasopressors.