Gain control with A-type potassium current: IA as a switch between divisive and subtractive inhibition

Neurons process information by transforming barrages of synaptic inputs into spiking activity. Synaptic inhibition suppresses the output firing activity of a neuron, and is commonly classified as having a subtractive or divisive effect on a neuron's output firing activity. Subtractive inhibition can narrow the range of inputs that evoke spiking activity by eliminating responses to non-preferred inputs. Divisive inhibition is a form of gain control: it modifies firing rates while preserving the range of inputs that evoke firing activity. Since these two "modes" of inhibition have distinct impacts on neural coding, it is important to understand the biophysical mechanisms that distinguish these response profiles. We use simulations and mathematical analysis of a neuron model to find the specific conditions for which inhibitory inputs have subtractive or divisive effects. We identify a novel role for the A-type Potassium current (IA). In our model, this fast-activating, slowly- inactivating outward current acts as a switch between subtractive and divisive inhibition. If IA is strong (large maximal conductance) and fast (activates on a time-scale similar to spike initiation), then inhibition has a subtractive effect on neural firing. In contrast, if IA is weak or insufficiently fast-activating, then inhibition has a divisive effect on neural firing. We explain these findings using dynamical systems methods to define how a spike threshold condition depends on synaptic inputs and IA. Our findings suggest that neurons can "self-regulate" the gain control effects of inhibition via combinations of synaptic plasticity and/or modulation of the conductance and kinetics of A-type Potassium channels. This novel role for IA would add flexibility to neurons and networks, and may relate to recent observations of divisive inhibitory effects on neurons in the nucleus of the solitary tract.Comment: 20 pages, 11 figure

Superconducting Films for Absorber-Coupled MKID Detectors for Sub-Millimeter and Far-Infrared Astronomy

We describe measurements of the properties, at dc, gigahertz, and terahertz frequencies, of thin (10 nm) aluminum films with 10 ohm/{rm square}$ normal state sheet resistance. Such films can be applied to construct microwave kinetic inductance detector arrays for submillimeter and far-infrared astronomical applications in which incident power excites quasiparticles directly in a superconducting resonator that is configured to present a matched-impedance to the high frequency radiation being detected. For films 10 nm thick, we report normal state sheet resistance, resistance-temperature curves for the superconducting transition, quality factor and kinetic inductance fraction for microwave resonators made from patterned films, and terahertz measurements of sheet impedance measured with a Fourier Transform Spectrometer. We compare properties with similar resonators made from niobium 600 nm thick

An investigation into perception of change in the foot-floor interface during repeated stretch-shortening cycles

Proprioceptive input is critical for normal and safe movement. There exists a gap in the literature regarding the assessment of proprioceptive function during dynamic tasks of the lower limb. To fill this gap, the present thesis has investigated perception of change in the foot-floor interface during repeated stretch-shortening cycles. This doctoral research serves as a foundation for considering proprioception as it pertains to dynamic function at the ankle

Radiation therapy generates platelet-activating factor agonists

Pro-oxidative stressors can suppress host immunity due to their ability to generate oxidized lipid agonists of the platelet-activating factor-receptor (PAF-R). As radiation therapy also induces reactive oxygen species, the present studies were designed to define whether ionizing radiation could generate PAF-R agonists and if these lipids could subvert host immunity. We demonstrate that radiation exposure of multiple tumor cell lines in-vitro, tumors in-vivo, and human subjects undergoing radiation therapy for skin tumors all generate PAF-R agonists. Structural characterization of radiation-induced PAF-R agonistic activity revealed PAF and multiple oxidized glycerophosphocholines that are produced non-enzymatically. In a murine melanoma tumor model, irradiation of one tumor augmented the growth of the other (non-treated) tumor in a PAF-R-dependent process blocked by a cyclooxygenase-2 inhibitor. These results indicate a novel pathway by which PAF-R agonists produced as a byproduct of radiation therapy could result in tumor treatment failure, and offer important insights into potential therapeutic strategies that could improve the overall antitumor effectiveness of radiation therapy regimens

Molecular Identity and Spatial Topography of Transient A-type Potassium Channels in the Rostral Nucleus of the Solitary Tract

The potent hedonic properties of tastes strongly affect dietary selection and are linked to clinical conditions associated with overconsumption and obesity. Understanding how taste is represented and processed in the brain is thus important to promote human health. CNS gustatory processing begins in the rostral nucleus of the solitary tract (rNST). Factors influencing the output signal from the rNST to areas that control ingestive behavior include the synaptic interactions of neurons within the nucleus and the intrinsic membrane properties of the neurons themselves. In particular, transient A-type potassium channels, which produce an outward IA current, have been shown to modulate sensory signals in both the caudal and rostral poles of the NST. However, the molecular identity of the IA channel on the two major phenotypes of neurons within the rNST, GABAergic interneurons and glutamatergic projection neurons, as well as the distribution of these channels within the different subdivisions of the rNST remains unclear. Previous literature suggest that IA is concentrated on non-GABAergic projection neurons in the central subdivision of rNST, while the channels are absent on GABAergic neurons in the ventral subdivision. However, we recently found that a subpopulation of GABAergic neurons do contain IA. Consequently, IA current is not exclusive to non-GABAergic projection cells, but exists on both cell phenotypes. In the present study, immunohistochemical and pharmacological approaches were used to identify the molecular identity of the potassium channel contributing to IA in the rNST and to describe its location within the nucleus. These data suggest that Kv4.3, a member of the Kv4 family, is primarily responsible for the IA current. Furthermore, it was observed that this channel is evenly distributed throughout the rNST, predominately in the neuropil, rather than on the cell soma. Pharmacologically blocking the IA channel using a toxin specific to the Kv4 family had similar effects on both GABAergic and non-GABAergic neurons. In both cell phenotypes the toxin reduced the first-spike delay and IA current amplitude seen in cells with IA. Because the expression of IA is sensitive to inhibition, we are exploring the interaction between IA and inhibition in sensory processing in the rNST.Research Supported by the NIH NIDCD Grant: ROIDC016112 Grant: R21DC013676Academic Major: Biolog

The microbiome of the gastrointestinal tract of a range-shifting marine herbivorous fish

Globally, marine species\u27 distributions are being modified due to rising ocean temperatures. Increasing evidence suggests a circum-global pattern of poleward extensions in the distributions of many tropical herbivorous species, including the ecologically important rabbitfis