Best Practices for Aripiprazole Lauroxil Administration: From Formulation Development to Injection Technique.

Long-acting injectable (LAI) antipsychotics are an important treatment option for patients with schizophrenia. Advances and variability in formulation technology have provided several LAI antipsychotic treatment options for schizophrenia, with a wide range of doses and dose intervals. However, clinical reviews of LAIs have not focused on formulation development despite its clinical relevance to injection safety and technique. This article reviews the relationship between formulation technology and clinical practices for LAIs, with a focus on aripiprazole lauroxil, a long-acting atypical antipsychotic indicated for the treatment of schizophrenia. The formulation developed for aripiprazole lauroxil is an aqueous-based suspension suitable for use as a prefilled syringe that, after injection, will release aripiprazole slowly into the plasma. The clinical relationship between the aripiprazole lauroxil formulation and proper injection techniques is explained, including why tapping and shaking the syringe to resuspend the drug particles and rapid injection speed are key steps for best injection practices for this formulation.

Computational mechanisms of mechanosensory processing in the cricket.

Crickets and many other orthopteran insects face the challenge of gathering sensory information from the environment from a set of multi-modal sensory organs and transforming these stimuli into patterns of neural activity that can encode behaviorally relevant stimuli. The cercal mechanosensory system transduces low frequency air movements near the animal's body and is involved in many behaviors including escape from predators, orientation with respect to gravity, flight steering, aggression and mating behaviors. Three populations of neurons are sensitive to both the direction and dynamics of air currents: an array of mechanoreceptor-coupled sensory neurons, identified local interneurons and identified projection interneurons. The sensory neurons form a functional map of air current direction within the central nervous system that represents the direction of air currents as three-dimensional spatio-temporal activity patterns. These dynamic activity patterns provide excitatory input to interneurons whose sensitivity and spiking output depend on the location of the neuronal arbors within the sensory map and the biophysical and electronic properties of the cell structure. Sets of bilaterally symmetric interneurons can encode the direction of an air current stimulus by their ensemble activity patterns, functioning much like a Cartesian coordinate system. These interneurons are capable of responding to specific dynamic stimuli with precise temporal patterns of action potentials that may encode these stimuli using temporal encoding schemes. Thus, a relatively simple mechanosensory system employs a variety of complex computational mechanisms to provide the animal with relevant information about its environment.

Dendritic design implements algorithm for synaptic extraction of sensory information.

While sensory information is encoded by firing patterns of individual sensory neurons, it is also represented by spatiotemporal patterns of activity in populations of the neurons. Postsynaptic interneurons decode the population response and extract specific sensory information. This extraction of information represented by presynaptic activities is a process critical to defining the input-output function of postsynaptic neuron. To understand the "algorithm" for the extraction, we examined directional sensitivities of presynaptic and postsynaptic Ca(2+) responses in dendrites of two types of wind-sensitive interneurons (INs) with different dendritic geometries in the cricket cercal sensory system. In IN 10-3, whose dendrites arborize with various electrotonic distances to the spike-initiating zone (SIZ), the directional sensitivity of dendritic Ca(2+) responses corresponded to those indicated by Ca(2+) signals in presynaptic afferents arborizing on that dendrite. The directional tuning properties of individual dendrites varied from each other, and the directional sensitivity of the nearest dendrite to the SIZ dominates the tuning properties of the spiking response. In IN 10-2 with dendrites isometric to the SIZ, directional tuning properties of different dendrites were similar to each other, and each response property could be explained by the directional profile of the spatial overlap between that dendrite and Ca(2+)-elevated presynaptic terminals. For IN 10-2, the directional sensitivities extracted by the different dendritic-branches would contribute equally to the overall tuning. It is possible that the differences in the distribution of synaptic weights because of the dendritic geometry are related to the algorithm for extraction of sensory information in the postsynaptic interneurons.

Visualization of ensemble activity patterns of mechanosensory afferents in the cricket cercal sensory system with calcium imaging.

The cercal sensory system of the cricket mediates the detection and analysis of low velocity air currents in the animal's immediate environment, and is implemented around an internal representation of air current direction that demonstrates the essential features of a continuous neural map. Previous neurophysiological and anatomical studies have yielded predictions of the global spatio-temporal patterns of activity that should be evoked in the sensory afferent map by air current stimuli of different directions. We tested those predictions by direct visualization of ensemble afferent activity patterns using Ca2+ -sensitive indicators. The AM ester of the fluorescent Ca2+ indicator (Oregon Green 488 BAPTA-1 AM) was injected under the sheath of a cercal sensory nerve containing all of the mechanosensory afferent axons from one cercus. Optical signals were recorded with a digital intensified CCD camera. Control experiments using direct electrical stimulation of stained and unstained nerves demonstrated that the observed Ca2+ signals within the terminal abdominal ganglion (TAG) were due to activation of the dye-loaded sensory afferent neurons. To visualize the spatial patterns of air-current-evoked ensemble activity, unidirectional air currents were applied repeatedly from eight different directions, and the optically recorded responses from each direction were averaged. The dispersion of the optical signals by the ganglion limited the spatial resolution with which these ensemble afferent activity patterns could be observed. However, resolution was adequate to demonstrate that different directional stimuli induced different spatial patterns of Ca2+ elevation in the terminal arbors of afferents within the TAG. These coarsely- resolved, optically-recorded patterns were consistent with the anatomy-based predictions.

NeuroSys: a semistructured laboratory database.

The inherent complexity of traditional relational database systems is a key obstacle to more widespread use of database technology in the neuroscience community. As an alternative to relational technology, we propose a simpler semistructured data model for documenting laboratory procedures and results. The semistructured data model allows researchers to document their data in an organized, regularly formatted, machine-readable, and network accessible manner, without requiring the services of database professionals. We present proof-of-concept software, consisting of an HTML interface that communicates with a remotely located, semistructured database. We also discuss the importance of standardized terminology and the importance of building flexible data description systems that are more easily adapted and reconfigured to conform with standardized terminologies as they evolve.