Highlights d All ORNs share a common dose-response function with variable sensitivity across odors d Sensitivities across odorants and ORNs follow a power-law distribution d Correlation in sensitivities corresponds to a geometric molecular property d ORN-odorant responses share similar temporal filters

We have developed a spinal cord surrogate for use in testing a pial-surface spinal cord stimulator. Our surrogate is of a commercially available silicone mix, has an oval cross-sectional area that matches that of actual human spinal cord at the lower thoracic level, and has measured values of durometer A = (10.96 ± 1.68), durometer O = (14.76 ± 1.48), and durometer OO = (50.24 ± 2.65). These correspond to model-inferred elastic moduli of 0.41 to 0.44 MPa, which match well with the existing low-strain rate measurements of ex vivo human spinal cord. Upcoming applications for this surrogate in developmental studies of the new stimulator system are discussed.

We have characterized the mechanical compliance of an improved version of the suspension system used to position the electrode-bearing membrane of an intradural neuromodulator on the dorsal pial surface of the spinal cord. Over the compression span of 5 mm, it exhibited a restoring force of 2.4 μN μm−1 and a mean pressure of 0.5 mm Hg (=66 Pa) on the surface below it, well within the range of normal intrathecal pressures. We have implanted prototype devices employing this suspension and a novel device fixation technique in a chronic ovine model of spinal cord stimulation and found that it maintains stable contact at the electrode-pia interface without lead fracture, as determined by measurement of the inter-contact impedances.

BackgroundNeurons form specific connections with targets via synapses and patterns of synaptic connectivity dictate neural function. During development, intrinsic neuronal specification and environmental factors guide both initial formation of synapses and strength of resulting connections. Once synapses form, non-evoked, spontaneous activity serves to modulate connections, strengthening some and eliminating others. Molecules that mediate intercellular communication are particularly important in synaptic refinement. Here, we characterize the influences of EphA4, a transmembrane signaling molecule, on neural connectivity.ResultsUsing multi-electrode array analysis on in vitro cultures, we confirmed that cortical neurons mature and generate spontaneous circuit activity as cells differentiate, with activity growing both stronger and more patterned over time. When EphA4 was over-expressed in a subset of neurons in these cultures, network activity was enhanced: bursts were longer and were composed of more spikes than in control-transfected cultures. To characterize the cellular basis of this effect, dendritic spines, the major excitatory input site on neurons, were examined on transfected neurons in vitro. Strikingly, while spine number and density were similar between conditions, cortical neurons with elevated levels of EphA4 had significantly more mature spines, fewer immature spines, and elevated colocalization with a mature synaptic marker.ConclusionsThese results demonstrate that experimental elevation of EphA4 promotes network activity in vitro, supporting spine maturation, producing more functional synaptic pairings, and promoting more active circuitry.

Internal state profoundly alters perception and behavior. For example, a starved fly may approach and consume foods that it would otherwise find undesirable. A socially engaged newt may remain engaged in the presence of a predator, whereas a solitary newt would otherwise attempt escape. Yet, the definition of internal state is fluid and ill-defined. As an interdisciplinary group of scholars spanning five career stages (from undergraduate to full professor) and six academic institutions, we have come together in an attempt to provide an operational definition of internal state that could be useful in understanding behavior and the function of nervous systems, at timescales relevant to the individual. In this Perspective, we propose to define internal state through an integrative framework centered on dynamic and interconnected communication loops in and between the body and the brain. This framework is informed by a synthesis of historical and contemporary paradigms used by neurobiologists, ethologists, physiologists, and endocrinologists. We view internal state as composed of both spatially distributed networks (body-brain communication loops), and temporally distributed mechanisms that weave together neural circuits, physiology, and behavior. Given the wide spatial and temporal scales at which internal state operates—and therefore the broad range of scales at which it could be defined—we choose to anchor our definition in the body. Here we focus on studies that highlight body-to-brain signaling; body represented in endocrine signaling, and brain represented in sensory signaling. This integrative framework of internal state potentially unites the disparate paradigms often used by scientists grappling with body-brain interactions. We invite others to join us as we examine approaches and question assumptions to study the underlying mechanisms and temporal dynamics of internal state.