Predation without direction selectivity.

Across the animal kingdom, visual predation relies on motion-sensing neurons in the superior colliculus (SC) and its orthologs. These neurons exhibit complex stimulus preferences, including direction selectivity, which is thought to be critical for tracking the unpredictable escape routes of prey. The source of direction selectivity in the SC is contested, and its contributions to predation have not been tested experimentally. Here, we use type-specific cell removal to show that narrow-field (NF) neurons in the mouse SC guide predation. In vivo recordings demonstrate that direction-selective responses of NF cells are independent of recently reported stimulus-edge effects. Monosynaptic retrograde tracing reveals that NF cells receive synaptic input from direction-selective ganglion cells. When we eliminate direction selectivity in the retina of adult mice, direction-selective responses in the SC, including in NF cells, are lost. However, eliminating retinal direction selectivity does not affect the hunting success or strategies of mice, even when direction selectivity is removed after mice have learned to hunt, and despite abolishing the gaze-stabilizing optokinetic reflex. Thus, our results identify the retinal source of direction selectivity in the SC. They show that NF cells in the SC guide predation, an essential spatial orienting task, independent of their direction selectivity, revealing behavioral multiplexing of complex neural feature preferences and highlighting the importance of feature-selective manipulations for neuroethology.

Diversity in homeostatic calcium set points predicts retinal ganglion cell survival following optic nerve injury in vivo.

Retinal ganglion cell (RGC) degeneration drives vision loss in blinding conditions. RGC death is often triggered by axon degeneration in the optic nerve. Here, we study the contributions of dynamic and homeostatic Ca2+ levels to RGC death from axon injury. We find that axonal Ca2+ elevations from optic nerve injury do not propagate over distance or reach RGC somas, and acute and chronic Ca2+ dynamics do not affect RGC survival. Instead, we discover that baseline Ca2+ levels vary widely between RGCs and predict their survival after axon injury, and that lowering these levels reduces RGC survival. Further, we find that well-surviving RGC types have higher baseline Ca2+ levels than poorly surviving types. Finally, we observe considerable variation in the baseline Ca2+ levels of different RGCs of the same type, which are predictive of within-type differences in survival.

Homeostatic plasticity in the retina.

Vision begins in the retina, whose intricate neural circuits extract salient features of the environment from the light entering our eyes. Neurodegenerative diseases of the retina (e.g., inherited retinal degenerations, age-related macular degeneration, and glaucoma) impair vision and cause blindness in a growing number of people worldwide. Increasing evidence indicates that homeostatic plasticity (i.e., the drive of a neural system to stabilize its function) can, in principle, preserve retinal function in the face of major perturbations, including neurodegeneration. Here, we review the circumstances and events that trigger homeostatic plasticity in the retina during development, sensory experience, and disease. We discuss the diverse mechanisms that cooperate to compensate and the set points and outcomes that homeostatic retinal plasticity stabilizes. Finally, we summarize the opportunities and challenges for unlocking the therapeutic potential of homeostatic plasticity. Homeostatic plasticity is fundamental to understanding retinal development and function and could be an important tool in the fight to preserve and restore vision.

Cell-type-specific binocular vision guides predation in mice.

Predators use vision to hunt, and hunting success is one of evolution's main selection pressures. However, how viewing strategies and visual systems are adapted to predation is unclear. Tracking predator-prey interactions of mice and crickets in 3D, we find that mice trace crickets with their binocular visual fields and that monocular mice are poor hunters. Mammalian binocular vision requires ipsi- and contralateral projections of retinal ganglion cells (RGCs) to the brain. Large-scale single-cell recordings and morphological reconstructions reveal that only a small subset (9 of 40+) of RGC types in the ventrotemporal mouse retina innervate ipsilateral brain areas (ipsi-RGCs). Selective ablation of ipsi-RGCs (<2% of RGCs) in the adult retina drastically reduces the hunting success of mice. Stimuli based on ethological observations indicate that five ipsi-RGC types reliably signal prey. Thus, viewing strategies align with a spatially restricted and cell-type-specific set of ipsi-RGCs that supports binocular vision to guide predation.

Differential Presynaptic ATP Supply for Basal and High-Demand Transmission.

The relative contributions of glycolysis and oxidative phosphorylation to neuronal presynaptic energy demands are unclear. In rat hippocampal neurons, ATP production by either glycolysis or oxidative phosphorylation alone sustained basal evoked synaptic transmission for up to 20 min. However, combined inhibition of both ATP sources abolished evoked transmission. Neither action potential propagation failure nor depressed Ca2+ influx explained loss of evoked synaptic transmission. Rather, inhibition of ATP synthesis caused massive spontaneous vesicle exocytosis, followed by arrested endocytosis, accounting for the disappearance of evoked postsynaptic currents. In contrast to its weak effects on basal transmission, inhibition of oxidative phosphorylation alone depressed recovery from vesicle depletion. Local astrocytic lactate shuttling was not required. Instead, either ambient monocarboxylates or neuronal glycolysis was sufficient to supply requisite substrate. In summary, basal transmission can be sustained by glycolysis, but strong presynaptic demands are met preferentially by oxidative phosphorylation, which can be maintained by bulk but not local monocarboxylates or by neuronal glycolysis.SIGNIFICANCE STATEMENT Neuronal energy levels are critical for proper CNS function, but the relative roles for the two main sources of ATP production, glycolysis and oxidative phosphorylation, in fueling presynaptic function in unclear. Either glycolysis or oxidative phosphorylation can fuel low-frequency synaptic function and inhibiting both underlies loss of synaptic transmission via massive vesicle release and subsequent failure to endocytose lost vesicles. Oxidative phosphorylation, fueled by either glycolysis or endogenously released monocarboxylates, can fuel more metabolically demanding tasks such as vesicle recovery after depletion. Our work demonstrates the flexible nature of fueling presynaptic function to maintain synaptic function.

A new fracture model for "terrible triad" injuries of the elbow: influence of forearm rotation on injury patterns.

OBJECTIVE: The purpose of this study was to evaluate the influence of forearm rotation on failure patterns of the elbow under axial loads. METHODS: Fourteen upper extremities were resected mid-humerus and mounted on a custom apparatus, which allowed rotation of the ulna, radius, and humerus about a fixed wrist while loading in axial compression. Seven specimens were loaded to failure with the forearm in pronation and 7 in supination. RESULTS: Six of the 7 elbows axially loaded in pronation resulted in fractures of the radial head and coronoid with posterior dislocation (terrible triad). Six of the 7 elbows loaded in supination dislocated without fracture. One of the 7 elbows tested in supination had a terrible triad-type elbow injury. Five of the 6 specimens with ulna external rotation had damage to the lateral ligaments; all 8 specimens with internal rotation had damage to the medial ligaments. There were no significant differences in biomechanical parameters between pronation and supination. CONCLUSIONS: The forearm position during axial load was the primary determinant of fracture-dislocation pattern. When the forearm was pronated, a terrible triad injury pattern most often occurred. When the forearm was supinated, a dislocation without fracture most often occurred. In both forearm rotation positions, when the ulna internally rotated during failure, the medial structures were the first to be disrupted. When the ulna externally rotated, the lateral structures were the first to be disrupted. Understanding the pathomechanics of elbow dislocation may improve diagnosis and treatment of these injuries.

Influence of distinct anatomic subregions of the supraspinatus on humeral rotation.

The supraspinatus, having distinct anterior and posterior subregions, is most commonly considered an abductor of the humerus, but it has also been shown to induce humeral rotation. The objective of this study was to quantify the magnitude and direction of humeral rotation that results from loading the distinct anterior and posterior subregions of the supraspinatus. Fourteen cadaver specimens were tested under four loading conditions based on physiological cross section area of the supraspinatus: (1) anterior only; (2) posterior only; (3) physiologic (each subregion loaded simultaneously); and (4) nonphysiologic (the tendon loaded as a whole). Each specimen was tested at 0, 15, 30, 45, and 60 degrees of glenohumeral abduction in the scapular plane and from 60 degrees of internal to 45 degrees of external rotation in 15 degrees increments. The humeral rotation that occurred with loading from the initial starting rotation position was measured using a rotary variable inductance transducer. In the scapular plane, the anterior subregion of the supraspinatus acts as both an internal and external rotator depending on the initial position of the humerus. The posterior subregion either acted as an external rotator or did not induce rotation. This study demonstrated a distinct functional difference between the anatomic subregions of the supraspinatus. This understanding will help to improve testing methods and the development of repair strategies of the supraspinatus.

Effects of flexor-pronator muscle loading on valgus stability of the elbow with an intact, stretched, and resected medial ulnar collateral ligament.

BACKGROUND: The medial ulnar collateral ligament (MUCL) is an important passive stabilizer to the valgus stresses that athletes experience during overhead throwing motion. However, the role of the flexor-pronator muscles as active stabilizers to valgus stress is not well defined in the literature. The objectives of this study were to quantify the relative contribution of the individual flexor-pronator muscles to valgus stability of the elbow and how this relationship was affected by ligament status. METHODS: A custom elbow testing system and Microscribe 3DLX were used for biomechanical testing. Flexor-pronator muscles were loaded to simulate contraction, and the valgus angle of the elbow was measured in eight cadaveric specimens at 30 degrees , 60 degrees , and 90 degrees of elbow flexion with 3 different valgus torques applied to the forearm. Loads based on muscle cross-sectional area were applied to the flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), and pronator teres (PT). The effect of each muscle was evaluated by unloading the individual muscle while the other 2 remained loaded, resulting in 5 loading conditions: no muscles loaded, all muscles loaded, unloaded FCU, unloaded FDS, and unloaded PT. Valgus angle was measured for 3 MUCL ligament conditions: intact, stretched, and cut. RESULTS: The effect of muscle loading on valgus angle was similar for each ligament condition. Loading the flexor-pronator muscles significantly decreased valgus angle of the elbow in all testing conditions (P < .01). Unloading the FDS significantly increased valgus angle compared to all muscles loaded in all testing conditions (P < .016). Unloading the FCU and PT significantly increased valgus angle in less than half of the testing conditions. CONCLUSION: The FDS, PT, and FCU are all active stabilizers of the elbow to valgus stress. The FDS is the biggest contributor amongst the flexor-pronator muscles.

NAMI perspective on CATIE: policy and research implications.

The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) was designed to assess effectiveness of antipsychotic medication for people with schizophrenia. The authors, who are administrators of the National Alliance on Mental Illness (NAMI), discuss CATIE and related policy and research studies and their implications. CATIE has answered some important questions for consumers and their families and raises many more. The prevalence of medical risk factors in the population with schizophrenia is an important part of advancing prevention. Poor adherence to medications randomly prescribed by CATIE physicians in a blinded procedure is also a key finding and points to the need for individually tailoring medication regimens. Policy makers may be tempted to oversimplify the results of CATIE by restricting access to the costlier second-generation medications. However, doing so will hurt clinical care, and any savings to state and community mental health programs may be illusory. Policy can be constructed to focus on clinical outcomes and not merely restrict access to medications on the basis of cost. Research is urgently needed on a new generation of medications with benign side effects and greater efficacy than their predecessors for people with schizophrenia.

Biomechanical assessment of Type II superior labral anterior-posterior (SLAP) lesions associated with anterior shoulder capsular laxity as seen in throwers: a cadaveric study.

BACKGROUND: Type II superior labral anterior-posterior lesions in throwers are often associated with anterior shoulder capsular laxity. HYPOTHESIS: Shoulder instability in patients with type II superior labral anterior-posterior lesions may result from the associated shoulder capsular laxity rather than the superior labral anterior-posterior lesion alone. STUDY DESIGN: Controlled laboratory study. METHODS: Six cadaveric shoulders were externally rotated to 20% beyond the maximum humeral external rotation at 60 degrees of glenohumeral abduction, which simulated 90 degrees of shoulder abduction, to detach the superior labrum and elongate the anterior shoulder capsular ligaments. The detached labrum was then repaired to isolate the effect of the detached superior labrum and that of the capsular laxity. Rotational range of motion was measured at 60 degrees of glenohumeral abduction. Anterior-posterior glenohumeral translation was measured at 30 degrees and 60 degrees of glenohumeral abduction. Superior-inferior glenohumeral translation was measured at 0 degrees and 60 degrees of glenohumeral abduction. RESULTS: The experimentally created type II superior labral anterior-posterior lesion and capsular laxity significantly increased anterior translation at 30 degrees (mean difference, 1.0 +/- 0.8 mm; P < .05) and 60 degrees (mean difference, 2.2 +/- 2.0 mm; P < .05) of glenohumeral abduction. Subsequent superior labral anterior-posterior repair restored the anterior translation but only at 30 degrees of glenohumeral abduction (mean difference, 0.9 +/- 0.6 mm; P < .05). CONCLUSION: Because of the anterior capsular laxity associated with type II superior labral anterior-posterior lesions, superior labral anterior-posterior repair of the peeled-back superior labrum may not restore anterior glenohumeral translation at 90 degrees of shoulder abduction. CLINICAL RELEVANCE: Anterior shoulder capsular laxity associated with type II superior labral anterior-posterior lesions may cause anterior shoulder instability at 90 degrees of shoulder abduction in throwers even after superior labral anterior-posterior lesion repair.

Biomechanical analysis of isolated type II SLAP lesions and repair.

The effects of type II superior labrum anterior-posterior (SLAP) lesions on glenohumeral rotation and translation were studied in 6 cadaveric shoulders before and after repair. Glenohumeral translation with the application of 15 N and 20 N in the anterior, posterior, superior, and inferior directions was measured with the joint in 60 degrees of abduction and 90 degrees of external rotation. Data were recorded for intact shoulders, shoulders with arthroscopy portals, shoulders with arthroscopically created anterior type II SLAP lesions, shoulders with arthroscopically created anterior and posterior type II SLAP lesions, and shoulders that had undergone arthroscopic repair. With the creation of a SLAP lesion, significant increases in total range of motion (P = .028), external rotation (P < .0001), internal rotation (P < .01), anterior-posterior translation (P < .0001), and inferior translation (P < .01) were observed. After arthroscopic repair, total range of motion, internal rotation, external rotation, and translation significantly decreased, returning to expected values. These findings suggest that type II SLAP lesions cause significant glenohumeral instability, which can be effectively treated with current arthroscopic techniques.

Development of cadaveric models of a thrower's shoulder.

Two novel cadaveric models of a thrower's shoulder were evaluated. Both models included the capsuloligamentous and osseous components of the glenohumeral joint. In model 1 the coracohumeral ligament was retained and the glenoid was positioned parallel to the ground whereas the humerus was positioned at 60 degrees of glenohumeral elevation in the scapular plane. In model 2 the coracohumeral ligament was resected and the glenoid was positioned vertically at 30 degrees of scapular elevation whereas the humerus was positioned at 60 degrees of glenohumeral elevation in the scapular plane. Each specimen was sequentially tested under 3 conditions: intact, after nondestructive anterior capsular stretch, and after simulated posterior capsular contracture. Measurements included rotational range of motion and relative glenohumeral position from neutral to maximum external rotation of the humerus. In model 2 the glenohumeral forces were also measured by use of a 6-degree-of-freedom load cell. The stretching of the anterior capsule in model 1 was performed while the humeral head was constrained in the glenoid and in model 2 while the humeral head was unconstrained. Both models showed increased humeral external rotation and decreased humeral internal rotation similar to that seen in throwing athletes. Both models also showed an increased humeral shift inferiorly after anterior capsular stretching. Model 1 demonstrated a subsequent humeral shift superiorly after posterior capsule plication. Unconstrained specimens of model 2 dislocated posteriorly and inferiorly after posterior capsule plication when the humerus was rotated to maximum external rotation. On the basis of these findings, for future studies, constrained capsular stretching models will be further investigated.