Telemedicine coverage for post-operative ICU patients.

Introduction There is an increased demand for intensive care unit (ICU) beds. We sought to determine if we could create a safe surge capacity model to increase ICU capacity by treating ICU patients in the post-anaesthesia care unit (PACU) utilizing a collaborative model between an ICU service and a telemedicine service during peak ICU bed demand. Methods We evaluated patients managed by the surgical critical care service in the surgical intensive care unit (SICU) compared to patients managed in the virtual intensive care unit (VICU) located within the PACU. A retrospective review of all patients seen by the surgical critical care service from January 1st 2008 to July 31st 2011 was conducted at an urban, academic, tertiary centre and level 1 trauma centre. Results Compared to the SICU group ( n = 6652), patients in the VICU group ( n = 1037) were slightly older (median age 60 (IQR 47-69) versus 58 (IQR 44-70) years, p = 0.002) and had lower acute physiology and chronic health evaluation (APACHE) II scores (median 10 (IQR 7-14) versus 15 (IQR 11-21), p \u3c 0.001). The average amount of time patients spent in the VICU was 13.7 + /-9.6 hours. In the VICU group, 750 (72%) of patients were able to be transferred directly to the floor; 287 (28%) required subsequent admission to the surgical intensive care unit. All patients in the VICU group were alive upon transfer out of the PACU while mortality in the surgical intensive unit cohort was 5.5%. Discussion A collaborative care model between a surgical critical care service and a telemedicine ICU service may safely provide surge capacity during peak periods of ICU bed demand. The specific patient populations for which this approach is most appropriate merits further investigation

Dissociation of somatostatin and parvalbumin interneurons circuit dysfunctions underlying hippocampal theta and gamma oscillations impaired by amyloid β oligomers in vivo

Accumulation of amyloid β oligomers (AβO) in Alzheimer’s disease (AD) impairs hippocampal theta and gamma oscillations. These oscillations are important in memory functions and depend on distinct subtypes of hippocampal interneurons such as somatostatin-positive (SST) and parvalbumin-positive (PV) interneurons. Here, we investigated whether AβO causes dysfunctions in SST and PV interneurons by optogenetically manipulating them during theta and gamma oscillations in vivo in AβO-injected SST-Cre or PV-Cre mice. Hippocampal in vivo multi-electrode recordings revealed that optogenetic activation of channelrhodopsin-2 (ChR2)-expressing SST and PV interneurons in AβO-injected mice selectively restored AβO-induced reduction of the peak power of theta and gamma oscillations, respectively, and resynchronized CA1 pyramidal cell (PC) spikes. Moreover, SST and PV interneuron spike phases were resynchronized relative to theta and gamma oscillations, respectively. Whole-cell voltage-clamp recordings in CA1 PC in ex vivo hippocampal slices from AβO-injected mice revealed that optogenetic activation of SST and PV interneurons enhanced spontaneous inhibitory postsynaptic currents (IPSCs) selectively at theta and gamma frequencies, respectively. Furthermore, analyses of the stimulus–response curve, paired-pulse ratio, and short-term plasticity of SST and PV interneuron-evoked IPSCs ex vivo showed that AβO increased the initial GABA release probability to depress SST/PV interneuron’s inhibitory input to CA1 PC selectively at theta and gamma frequencies, respectively. Our results reveal frequency-specific and interneuron subtype-specific presynaptic dysfunctions of SST and PV interneurons’ input to CA1 PC as the synaptic mechanisms underlying AβO-induced impairments of hippocampal network oscillations and identify them as potential therapeutic targets for restoring hippocampal network oscillations in early AD

Quasi-simultaneous multiplane calcium imaging of neuronal circuits

Two-photon excitation fluorescence microscopy is widely used to study the activity of neuronal circuits. However, the fast imaging is typically constrained to a single lateral plane for a standard microscope design. Given that cortical neuronal networks in a mouse brain are complex three-dimensional structures organised in six histologically defined layers which extend over many hundreds of micrometres, there is a strong demand for microscope systems that can record neuronal signalling in volumes. Henceforth, we developed a quasi-simultaneous multiplane imaging technique combining acousto-optic deflector and static remote focusing to provide fast imaging of neurons from different axial positions inside the cortical layers without the need for the mechanical interference of either the objective lens or the specimen. The hardware and the software are easily adaptable to existing two-photon microscopes. Here, we demonstrated that our imaging method can record, at high speed and high image contrast, the calcium dynamics of neurons in two different imaging planes separated axially, with the in-focus and the refocused planes 120 μm and 250 μm below the brain surface respectively

Electrical conductivity, ionic conductivity, optical absorption, and gas separation properties of ionically conductive polymer membranes embedded with Si microwire arrays

The optical absorption, ionic conductivity, electronic conductivity, and gas separation properties have been evaluated for flexible composite films of ionically conductive polymers that contain partially embedded arrays of ordered, crystalline, p-type Si microwires. The cation exchange ionomer Nafion, and a recently developed anion exchange ionomer, poly(arylene ether sulfone) that contains quaternary ammonium groups (QAPSF), produced composite microwire array/ionomer membrane films that were suitable for operation in acidic or alkaline media, respectively. The ionic conductivity of the Si wire array/Nafion composite films in 2.0 M H_(2)SO_4(aq) was 71 mS cm^(−1), and the conductivity of the Si wire array/QAPSF composite films in 2.0 M KOH(aq) was 6.4 mS cm^(−1). Both values were comparable to the conductivities observed for films of these ionomers that did not contain embedded Si wire arrays. Two Si wire array/Nafion membranes were electrically connected in series, using a conducting polymer, to produce a trilayer, multifunctional membrane that exhibited an ionic conductivity in 2.0 M H_(2)SO)4(aq) of 57 mS cm^(−1) and an ohmic electrical contact, with an areal resistance of ~0.30 Ω cm^2, between the two physically separate embedded Si wire arrays. All of the wire array/ionomer composite membranes showed low rates of hydrogen crossover. Optical measurements indicated very low absorption (<3%) in the ion-exchange polymers but high light absorption (up to 80%) by the wire arrays even at normal incidence, attesting to the suitability of such multifunctional membranes for application in solar fuels production

Distinct roles of parvalbumin and somatostatin interneurons in gating the synchronization of spike-times in the neocortex

Synchronization of precise spike times across multiple neurons carries information about sensory stimuli. Inhibitory interneurons are suggested to promote this synchronization, but it is unclear whether distinct interneuron subtypes provide different contributions. To test this, we examined single-unit recordings from barrel cortex in vivo and used optogenetics to determine the contribution of parvalbumin (PV)– and somatostatin (SST)–positive interneurons to the synchronization of spike times across cortical layers. We found that PV interneurons preferentially promote the synchronization of spike times when instantaneous firing rates are low (&lt;12 Hz), whereas SST interneurons preferentially promote the synchronization of spike times when instantaneous firing rates are high (&gt;12 Hz). Furthermore, using a computational model, we demonstrate that these effects can be explained by PV and SST interneurons having preferential contributions to feedforward and feedback inhibition, respectively. Our findings demonstrate that distinct subtypes of inhibitory interneurons have frequency-selective roles in the spatiotemporal synchronization of precise spike times

Memory encoding and retrieval by retrosplenial parvalbumin interneurons is impaired in Alzheimer's disease model mice

Memory deficits in Alzheimer’s disease (AD) show a strong link with GABAergic interneuron dysfunctions.1,2,3,4,5,6,7 The ensemble dynamics of GABAergic interneurons represent memory encoding and retrieval,8,9,10,11,12 but how GABAergic interneuron dysfunction affects inhibitory ensemble dynamics in AD is unknown. As the retrosplenial cortex (RSC) is critical for episodic memory13,14,15,16 and is affected by β-amyloid accumulation in early AD,17,18,19,20,21 we address this question by performing Ca2+ imaging in RSC parvalbumin (PV)-expressing interneurons during a contextual fear memory task in healthy control mice and the 5XFAD mouse model of AD. We found that populations of PV interneurons responsive to aversive electric foot shocks during contextual fear conditioning (shock-responsive) significantly decreased in the 5XFAD mice, indicating dysfunctions in the recruitment of memory-encoding PV interneurons. In the control mice, ensemble activities of shock-responsive PV interneurons were selectively upregulated during the freezing epoch of the contextual fear memory retrieval, manifested by synaptic potentiation of PV interneuron-mediated inhibition. However, such changes in ensemble dynamics during memory retrieval and synaptic plasticity were both absent in the 5XFAD mice. Optogenetic silencing of PV interneurons during contextual fear conditioning in the control mice mimicked the memory deficits in the 5XFAD mice, while optogenetic activation of PV interneurons in the 5XFAD mice restored memory retrieval. These results demonstrate the critical roles of contextual fear memory-encoding PV interneurons for memory retrieval. Furthermore, synaptic dysfunction of PV interneurons may disrupt the recruitment of PV interneurons and their ensemble dynamics underlying contextual fear memory retrieval, subsequently leading to memory deficits in AD

Optogenetic activation of parvalbumin and somatostatin interneurons selectively restores theta-nested gamma oscillations and oscillation-induced spike timing-dependent long-term potentiation impaired by amyloid β oligomers

BACKGROUND: Abnormal accumulation of amyloid β1-42 oligomers (AβO1-42), a hallmark of Alzheimer's disease, impairs hippocampal theta-nested gamma oscillations and long-term potentiation (LTP) that are believed to underlie learning and memory. Parvalbumin-positive (PV) and somatostatin-positive (SST) interneurons are critically involved in theta-nested gamma oscillogenesis and LTP induction. However, how AβO1-42 affects PV and SST interneuron circuits is unclear. Through optogenetic manipulation of PV and SST interneurons and computational modeling of the hippocampal neural circuits, we dissected the contributions of PV and SST interneuron circuit dysfunctions on AβO1-42-induced impairments of hippocampal theta-nested gamma oscillations and oscillation-induced LTP. RESULTS: Targeted whole-cell patch-clamp recordings and optogenetic manipulations of PV and SST interneurons during in vivo-like, optogenetically induced theta-nested gamma oscillations in vitro revealed that AβO1-42 causes synapse-specific dysfunction in PV and SST interneurons. AβO1-42 selectively disrupted CA1 pyramidal cells (PC)-to-PV interneuron and PV-to-PC synapses to impair theta-nested gamma oscillogenesis. In contrast, while having no effect on PC-to-SST or SST-to-PC synapses, AβO1-42 selectively disrupted SST interneuron-mediated disinhibition to CA1 PC to impair theta-nested gamma oscillation-induced spike timing-dependent LTP (tLTP). Such AβO1-42-induced impairments of gamma oscillogenesis and oscillation-induced tLTP were fully restored by optogenetic activation of PV and SST interneurons, respectively, further supporting synapse-specific dysfunctions in PV and SST interneurons. Finally, computational modeling of hippocampal neural circuits including CA1 PC, PV, and SST interneurons confirmed the experimental observations and further revealed distinct functional roles of PV and SST interneurons in theta-nested gamma oscillations and tLTP induction. CONCLUSIONS: Our results reveal that AβO1-42 causes synapse-specific dysfunctions in PV and SST interneurons and that optogenetic modulations of these interneurons present potential therapeutic targets for restoring hippocampal network oscillations and synaptic plasticity impairments in Alzheimer's disease

Porphyrin dyes for nonlinear optical imaging of live cells

Second harmonic generation (SHG)-based probes are useful for nonlinear optical imaging of biological structures, such as the plasma membrane. Several amphiphilic porphyrin-based dyes with high SHG coefficients have been synthesized with different hydrophilic head groups, and their cellular targeting has been studied. The probes with cationic head groups localize better at the plasma membrane than the neutral probes with zwitterionic or non-charged ethylene glycol-based head groups. Porphyrin dyes with only dications as hydrophilic head groups localize inside HEK293T cells to give SHG, whereas tricationic dyes localize robustly at the plasma membrane of cells, including neurons, in vitro and ex vivo. The copper(II) complex of the tricationic dye with negligible fluorescence quantum yield works as an SHG-only dye. The free-base tricationic dye has been demonstrated for two-photon fluorescence and SHG-based multimodal imaging. This study demonstrates the importance of a balance between the hydrophobicity and hydrophilicity of amphiphilic dyes for effective plasma membrane localization

Left-right dissociation of hippocampal memory processes in mice.

Left-right asymmetries have likely evolved to make optimal use of bilaterian nervous systems; however, little is known about the synaptic and circuit mechanisms that support divergence of function between equivalent structures in each hemisphere. Here we examined whether lateralized hippocampal memory processing is present in mice, where hemispheric asymmetry at the CA3-CA1 pyramidal neuron synapse has recently been demonstrated, with different spine morphology, glutamate receptor content, and synaptic plasticity, depending on whether afferents originate in the left or right CA3. To address this question, we used optogenetics to acutely silence CA3 pyramidal neurons in either the left or right dorsal hippocampus while mice performed hippocampus-dependent memory tasks. We found that unilateral silencing of either the left or right CA3 was sufficient to impair short-term memory. However, a striking asymmetry emerged in long-term memory, wherein only left CA3 silencing impaired performance on an associative spatial long-term memory task, whereas right CA3 silencing had no effect. To explore whether synaptic properties intrinsic to the hippocampus might contribute to this left-right behavioral asymmetry, we investigated the expression of hippocampal long-term potentiation. Following the induction of long-term potentiation by high-frequency electrical stimulation, synapses between CA3 and CA1 pyramidal neurons were strengthened only when presynaptic input originated in the left CA3, confirming an asymmetry in synaptic properties. The dissociation of hippocampal long-term memory function between hemispheres suggests that memory is routed via distinct left-right pathways within the mouse hippocampus, and provides a promising approach to help elucidate the synaptic basis of long-term memory.http://dx.doi.org/10.1073/pnas.1405648111This is the author's accepted manuscript. It will be under embargo for 6 months from the date of publication. The final version is available from PNAS at http://www.pnas.org/content/early/2014/09/16/1405648111.abstract