Theta and gamma rhythmic coding through two spike output modes in the hippocampus during spatial navigation.

Hippocampal CA1 neurons generate single spikes and stereotyped bursts of spikes. However, it is unclear how individual neurons dynamically switch between these output modes and whether these two spiking outputs relay distinct information. We performed extracellular recordings in spatially navigating rats and cellular voltage imaging and optogenetics in awake mice. We found that spike bursts are preferentially linked to cellular and network theta rhythms (3-12 Hz) and encode an animal's position via theta phase precession, particularly as animals are entering a place field. In contrast, single spikes exhibit additional coupling to gamma rhythms (30-100 Hz), particularly as animals leave a place field. Biophysical modeling suggests that intracellular properties alone are sufficient to explain the observed input frequency-dependent spike coding. Thus, hippocampal neurons regulate the generation of bursts and single spikes according to frequency-specific network and intracellular dynamics, suggesting that these spiking modes perform distinct computations to support spatial behavior.

Striatal cholinergic interneuron membrane voltage tracks locomotor rhythms in mice.

Rhythmic neural network activity has been broadly linked to behavior. However, it is unclear how membrane potentials of individual neurons track behavioral rhythms, even though many neurons exhibit pace-making properties in isolated brain circuits. To examine whether single-cell voltage rhythmicity is coupled to behavioral rhythms, we focused on delta-frequencies (1-4 Hz) that are known to occur at both the neural network and behavioral levels. We performed membrane voltage imaging of individual striatal neurons simultaneously with network-level local field potential recordings in mice during voluntary movement. We report sustained delta oscillations in the membrane potentials of many striatal neurons, particularly cholinergic interneurons, which organize spikes and network oscillations at beta-frequencies (20-40 Hz) associated with locomotion. Furthermore, the delta-frequency patterned cellular dynamics are coupled to animals' stepping cycles. Thus, delta-rhythmic cellular dynamics in cholinergic interneurons, known for their autonomous pace-making capabilities, play an important role in regulating network rhythmicity and movement patterning.

Deep brain stimulation creates informational lesion through membrane depolarization in mouse hippocampus.

Deep brain stimulation (DBS) is a promising neuromodulation therapy, but the neurophysiological mechanisms of DBS remain unclear. In awake mice, we performed high-speed membrane voltage fluorescence imaging of individual hippocampal CA1 neurons during DBS delivered at 40 Hz or 140 Hz, free of electrical interference. DBS powerfully depolarized somatic membrane potentials without suppressing spike rate, especially at 140 Hz. Further, DBS paced membrane voltage and spike timing at the stimulation frequency and reduced timed spiking output in response to hippocampal network theta-rhythmic (3-12 Hz) activity patterns. To determine whether DBS directly impacts cellular processing of inputs, we optogenetically evoked theta-rhythmic membrane depolarization at the soma. We found that DBS-evoked membrane depolarization was correlated with DBS-mediated suppression of neuronal responses to optogenetic inputs. These results demonstrate that DBS produces powerful membrane depolarization that interferes with the ability of individual neurons to respond to inputs, creating an informational lesion.

Comparison of the fixation strength of standard and fenestrated stent-grafts for endovascular abdominal aortic aneurysm repair.

PURPOSE: To determine whether fenestrated stent-grafts provide better stability to resist migration than standard non-fenestrated stent-grafts. METHODS: Truncated fenestrated stent-grafts with a single fenestration were deployed in bovine aortic segments with a side branch. Balloon-expandable stents were then delivered into the branches. Similarly, standard stent-grafts of the same dimensions were deployed for comparison. The aorta was pressurized to achieve stent-graft oversizing of 5%, 10%, or 20%. The force required to cause distal migration was recorded by a digital force gauge attached to the stent-graft. RESULTS: Displacement of the stent-grafts occurred in 2 distinct phases: an initial yield during which the barbs embedded in the aortic wall and a final displacement leading to significant migration and dislodgement of the device. The displacement force that initiated each phase was dependent upon the degree of oversizing of the stent-graft relative to the aortic diameter. For 5%, 10%, and 20% oversizing, the mean displacement forces in the initial displacement phase were 3.39+/-0.37, 4.32+/-0.63, and 7.69+/-1.18 N, respectively, in non-fenestrated grafts and 10.48+/-1.23, 11.45+/-1.48, 12.12+/-1.42 N in fenestrated grafts. The displacement forces in the final displacement phase were 8.10+/-0.92, 10.76+/-1.74, and 16.82+/-0.92 N for non-fenestrated and 22.56+/-1.60, 28.24+/-1.56, and 33.01+/-1.75 N for fenestrated stent-grafts. The differences in displacement forces between standard and fenestrated stent-grafts were significant for both phases (p<0.001) at all oversizing levels. CONCLUSION: Improvement in fixation strength was noted with increasing stent-graft oversizing of up to 20%. Fenestrated stent-grafts offer higher ultimate fixation compared to standard devices. However, the ultimate fixation strength was not recruited until an initial phase of short migration occurred as the barbs engaged. While this movement is inconsequential with standard stent-grafts, it has the potential to crush the stents placed into aortic side branches with fenestrated endografts.