Correlation Between Lumbopelvic and Sagittal Parameters and Health-Related Quality of Life in Adults With Lumbosacral Spondylolisthesis.

Study Design:Secondary analysis of prospective, multicenter data. Objective:To evaluate impact of sagittal parameters on health-related quality of life (HRQoL) in adults with lumbosacral spondylolisthesis. Methods:Adults with unoperated lumbosacral spondylolisthesis were identified in the Spinal Deformity Study Group database. Pearson's correlations were calculated between SF-12 (Short Form-12)/Scoliosis Research Society-30 (SRS-30) scores and radiographic parameters (C7 sagittal vertical axis [SVA] deviation, T1 pelvic angle, pelvic tilt [PT], pelvic incidence, sacral slope, slip angle, Meyerding slip grade, Labelle classification). Main effects linear regression models measured association between individual health status measures and individual radiographic predictor variables. Results:Forty-five patients were analyzed (male, 15; female, 30; average age 40.5 ± 18.7 years; 14 low-grade, 31 high-grade). For low-grade slips, SVA had strong negative correlations with SF-12 mental component score (MCS), SRS-30 appearance, mental, and satisfaction domains (r = -0.57, r = -0.60, r = -0.58, r = -0.53, respectively; P < .05). For high-grade slips, slip angle had a moderate negative correlation with SF-12 MCS (r = -0.36; P = .05) and SVA had strong negative correlations with SF-12 physical component score (PCS), SRS-30 appearance and activity domains (r = -0.48, r = -0.48, r = -0.45; P < .05) and a moderate negative correlation with SRS-30 total (r = -0.37; P < .05). T1 pelvic angle had a moderate negative correlation with SF-12 PCS and SRS-30 appearance (r = -0.37, r = -0.36; P ≤ .05). For every 1° increase in PT, there was a 0.04-point decrease in SRS appearance, 0.05-point decrease in SRS activity, 0.06-point decrease in SRS satisfaction, and 0.04-point decrease in SRS total score (P < .05). Conclusion:Lumbosacral spondylolisthesis in adults negatively affects HRQoL. Multiple radiographic sagittal parameters negatively affect HRQoLs for patients with low- and high-grade slips. Improvement of sagittal parameters is an important goal of surgery for adults with lumbosacral spondylolisthesis

Molecular identification of a retinal cell type that responds to upward motion

The retina contains complex circuits of neurons that extract salient information from visual inputs. Signals from photoreceptors are processed by retinal interneurons, integrated by retinal ganglion cells (RGCs) and sent to the brain by RGC axons. Distinct types of RGC respond to different visual features, such as increases or decreases in light intensity (ON and OFF cells, respectively), colour or moving objects1, 2, 3, 4, 5. Thus, RGCs comprise a set of parallel pathways from the eye to the brain. The identification of molecular markers for RGC subsets will facilitate attempts to correlate their structure with their function, assess their synaptic inputs and targets, and study their diversification. Here we show, by means of a transgenic marking method, that junctional adhesion molecule B (JAM-B) marks a previously unrecognized class of OFF RGCs in mice. These cells have asymmetric dendritic arbors aligned in a dorsal-to-ventral direction across the retina. Their receptive fields are also asymmetric and respond selectively to stimuli moving in a soma-to-dendrite direction; because the lens reverses the image of the world on the retina, these cells detect upward motion in the visual field. Thus, JAM-B identifies a unique population of RGCs in which structure corresponds remarkably to function

NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells

Postsynaptic AMPA‐ and NMDA‐type glutamate receptors (AMPARs, NMDARs) are commonly expressed at the same synapses. AMPARs are thought to mediate the majority of fast excitatory neurotransmission whereas NMDARs, with their relatively slower kinetics and higher Ca 2+ permeability, are thought to mediate synaptic plasticity, especially in neural circuits devoted to learning and memory. In sensory neurons, however, the roles of AMPARs and NMDARs are less well understood. Here, we tested in the in vitro guinea pig retina whether AMPARs and NMDARs differentially support temporal contrast encoding by two ganglion cell types. In both OFF Alpha and Delta ganglion cells, contrast stimulation evoked an NMDAR‐mediated response with a characteristic J‐shaped I–V relationship. In OFF Delta cells, AMPAR‐ and NMDAR‐mediated responses could be modulated at low frequencies but were suppressed during 10 Hz stimulation, when responses were instead shaped by synaptic inhibition. With inhibition blocked, both AMPAR‐ and NMDAR‐mediated responses could be modulated at 10 Hz, indicating that NMDAR kinetics do not limit temporal encoding. In OFF Alpha cells, NMDAR‐mediated responses followed stimuli at frequencies up to ∼18 Hz. In both cell types, NMDAR‐mediated responses to contrast modulation at 9–18 Hz showed delays of <10 ms relative to AMPAR‐mediated responses. Thus, NMDARs combine with AMPARs to encode rapidly modulated glutamate release, and NMDAR kinetics do not limit temporal coding by OFF Alpha and Delta ganglion cells substantially. Furthermore, glutamatergic transmission is differentially regulated across bipolar cell pathways: in some, release is suppressed at high temporal frequencies by presynaptic inhibition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109576/1/tjp6355.pd

Computational and Molecular Properties of Starburst Amacrine Cell Synapses Differ With Postsynaptic Cell Type

&lt;jats:p&gt;A presynaptic neuron can increase its computational capacity by transmitting functionally distinct signals to each of its postsynaptic cell types. To determine whether such computational specialization occurs over fine spatial scales within a neurite arbor, we investigated computation at output synapses of the starburst amacrine cell (SAC), a critical component of the classical direction-selective (DS) circuit in the retina. The SAC is a non-spiking interneuron that co-releases GABA and acetylcholine and forms closely spaced (&amp;amp;lt;5 μm) inhibitory synapses onto two postsynaptic cell types: DS ganglion cells (DSGCs) and neighboring SACs. During dynamic optogenetic stimulation of SACs in mouse retina, whole-cell recordings of inhibitory postsynaptic currents revealed that GABAergic synapses onto DSGCs exhibit stronger low-pass filtering than those onto neighboring SACs. Computational analyses suggest that this filtering difference can be explained primarily by presynaptic properties, rather than those of the postsynaptic cells &lt;jats:italic&gt;per se&lt;/jats:italic&gt;. Consistent with functionally diverse SAC presynapses, blockade of N-type voltage-gated calcium channels abolished GABAergic currents in SACs but only moderately reduced GABAergic and cholinergic currents in DSGCs. These results jointly demonstrate how specialization of synaptic outputs could enhance parallel processing in a compact interneuron over fine spatial scales. Moreover, the distinct transmission kinetics of GABAergic SAC synapses are poised to support the functional diversity of inhibition within DS circuitry.&lt;/jats:p&gt

NMDA and AMPA receptors contribute similarly to temporal processing in mammalian retinal ganglion cells

Postsynaptic AMPA‐ and NMDA‐type glutamate receptors (AMPARs, NMDARs) are commonly expressed at the same synapses. AMPARs are thought to mediate the majority of fast excitatory neurotransmission whereas NMDARs, with their relatively slower kinetics and higher Ca 2+ permeability, are thought to mediate synaptic plasticity, especially in neural circuits devoted to learning and memory. In sensory neurons, however, the roles of AMPARs and NMDARs are less well understood. Here, we tested in the in vitro guinea pig retina whether AMPARs and NMDARs differentially support temporal contrast encoding by two ganglion cell types. In both OFF Alpha and Delta ganglion cells, contrast stimulation evoked an NMDAR‐mediated response with a characteristic J‐shaped I–V relationship. In OFF Delta cells, AMPAR‐ and NMDAR‐mediated responses could be modulated at low frequencies but were suppressed during 10 Hz stimulation, when responses were instead shaped by synaptic inhibition. With inhibition blocked, both AMPAR‐ and NMDAR‐mediated responses could be modulated at 10 Hz, indicating that NMDAR kinetics do not limit temporal encoding. In OFF Alpha cells, NMDAR‐mediated responses followed stimuli at frequencies up to ∼18 Hz. In both cell types, NMDAR‐mediated responses to contrast modulation at 9–18 Hz showed delays of <10 ms relative to AMPAR‐mediated responses. Thus, NMDARs combine with AMPARs to encode rapidly modulated glutamate release, and NMDAR kinetics do not limit temporal coding by OFF Alpha and Delta ganglion cells substantially. Furthermore, glutamatergic transmission is differentially regulated across bipolar cell pathways: in some, release is suppressed at high temporal frequencies by presynaptic inhibition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109576/1/tjp6355.pd

Complexin 3 increases the fidelity of signaling in a retinal circuit by regulating exocytosis at ribbon synapses

SummaryComplexin (Cplx) proteins modulate the core SNARE complex to regulate exocytosis. To understand the contributions of Cplx to signaling in a well-characterized neural circuit, we investigated how Cplx3, a retina-specific paralog, shapes transmission at rod bipolar (RB)→AII amacrine cell synapses in the mouse retina. Knockout of Cplx3 strongly attenuated fast, phasic Ca2+-dependent transmission, dependent on local [Ca2+] nanodomains, but enhanced slower Ca2+-dependent transmission, dependent on global intraterminal [Ca2+] ([Ca2+]I). Surprisingly, coordinated multivesicular release persisted at Cplx3−/− synapses, although its onset was slowed. Light-dependent signaling at Cplx3−/− RB→AII synapses was sluggish, owing largely to increased asynchronous release at light offset. Consequently, propagation of RB output to retinal ganglion cells was suppressed dramatically. Our study links Cplx3 expression with synapse and circuit function in a specific retinal pathway and reveals a role for asynchronous release in circuit gain control