Bone conducted responses in the neonatal rat auditory cortex

Rats are born deaf and start hearing at the end of the second postnatal week, when the ear canals open and low-intensity sounds start to evoke responses in the auditory cortex. Here, using μECoG electrode arrays and intracortical silicon probe recordings, we found that bone-conducted (BC) sounds evoked biphasic responses in the auditory cortex starting from postnatal day (P) 8. The initial phase of these responses, generated by thalamocortical input, was followed by intracortical propagation within supragranular layers. BC-evoked responses co-localized with the responses evoked by electrical stimulation of the cochlea and the deepest layers of the inferior colliculus prior to onset of low-threshold hearing (P13), as well as with the responses evoked by high-frequency (30 kHz) low-intensity (70 dB) air-conducted sounds after that. Thus, BC signals reach high-frequency processing regions of the auditory cortex well before the onset of low-threshold hearing, reflecting early integrity of the auditory system.

Bone-conducted Responses in the Neonatal rat Auditory Cortex

Rats are born deaf and start hearing at the end of the second postnatal week, when the ear canals open and low-intensity sounds start to evoke responses in the auditory cortex. Here, using µECoG electrode arrays and intracortical silicon probe recordings, we found that bone-conducted (BC) sounds evoked biphasic responses in the auditory cortex starting from postnatal day (P) 8. The initial phase of these responses, generated by thalamocortical input, was followed by intracortical propagation within supragranular layers. BC-evoked responses co-localized with the responses evoked by electrical stimulation of the cochlea and the deepest layers of the inferior colliculus prior to onset of low-threshold hearing (P13), as well as with the responses evoked by high-frequency (30 kHz) low-intensity (70 dB) air-conducted sounds after that. Thus, BC signals reach high-frequency processing regions of the auditory cortex well before the onset of low-threshold hearing, reflecting early integrity of the auditory system.

Sex differences in somatotrope response to fasting: biphasic responses in male mice

Anterior pituitary somatotropes are important metabolic sensors responding to leptin by secreting growth hormone (GH). However, reduced leptin signals caused by fasting have not always correlated with reduced serum GH. Reports show that fasting may stimulate or reduce GH secretion, depending on the species. Mechanisms underlying these distinct somatotrope responses to fasting remain unknown. To define the somatotrope response to decreased leptin signaling we examined markers of somatotrope function over different time periods of fasting. Male mice were fasted for 24 and 48 h, with female mice fasted for 24 h compared to fed controls ad libitum. Body weight and serum glucose were reduced in both males and females, but, unexpectedly, serum leptin was reduced only in males. Furthermore, in males, serum GH levels showed a biphasic response with significant reductions at 24 h followed by a significant rise at 48 h, which coincided with the rise in serum ghrelin levels. In contrast, females showed an increase in serum GH at 24 h. We then explored mechanisms underlying the differential somatotrope responses seen in males and observed that pituitary levels of Gh mRNA increased, with no distinction between acute and prolonged fasting. By contrast, the Ghrhr mRNA (encoding GH releasing hormone receptor) and the Ghsr mRNA (encoding the ghrelin receptor) were both greatly increased at prolonged fasting times coincident with increased serum GH. These findings show sex differences in the somatotrope and adipocyte responses to fasting and support an adaptive role for somatotropes in males in response to multiple metabolic signals.

Exploring cyclic networks of multisite modification reveals origins of information processing characteristics

Multisite phosphorylation (and generally multisite modification) is a basic way of encoding substrate function and circuits/networks of post-translational modifications (PTM) are ubiquitous in cell signalling. The information processing characteristics of PTM systems are a focal point of broad interest. The ordering of modifications is a key aspect of multisite modification, and a broad synthesis of the impact of ordering of modifications is still missing. We focus on a basic class of multisite modification circuits: the cyclic mechanism, which corresponds to the same ordering of phosphorylation and dephosphorylation, and examine multiple variants involving common/separate kinases and common/separate phosphatases. This is of interest both because it is encountered in concrete cellular contexts, and because it serves as a bridge between ordered (sequential) mechanisms (representing one type of ordering) and random mechanisms (which have no ordering). We show that bistability and biphasic dose response curves of the maximally modified phosphoform are ruled out for basic structural reasons independent of parameters, while oscillations can result with even just one shared enzyme. We then examine the effect of relaxing some basic assumptions about the ordering of modification. We show computationally and analytically how bistability, biphasic responses and oscillations can be generated by minimal augmentations to the cyclic mechanism even when these augmentations involved reactions operating in the unsaturated limit. All in all, using this approach we demonstrate (1) how the cyclic mechanism (with single augmentations) represents a modification circuit using minimal ingredients (in terms of shared enzymes and sequestration of enzymes) to generate bistability and oscillations, when compared to other mechanisms, (2) new design principles for rationally designing PTM systems for a variety of behaviour, (3) a basis and a necessary step for understanding the origins and robustness of behaviour observed in basic multisite modification systems.

Detailed insight into transtympanic electrocochleography (TT-ECochG) and direct cochlear nerve action potential (CNAP) for intraoperative hearing monitoring in patients with vestibular schwannoma – methodology of measurements and interpretation of results

<b>Background:</b> The aim was to present the methodology and interpretation of intraoperative hearing monitoring with simultaneous Transtympanic Electrocochleography (TT-ECochG) and direct Cochlear Nerve Action Potential (CNAP) measurements during vestibular schwannoma removal. <br><b>Materials and Methods:</b> Detailed methodology of measurements and interpretation of results are presented in three exemplary patients who underwent tumor removal via middle fossa approach (MFA) with the use of intraoperative monitoring of hearing with TT-ECochG and direct CNAP performed in real time. In addition, all responses were automatically recorded and stored along with surgical information and subjected to detailed analyses and calculation after surgery. <br><b>Results:</b> The following changes in TT-ECochG and direct CNAP responses were observed: Patient #1 – TT-ECochG and CNAP responses with minor, but transient, morphology changes (hearing was preserved); Patient #2 – CNAP responses changed significantly but, temporarily, from triphasic into biphasic responses later, with marked but partially reversible desynchronization of CNAP; changes in TT-ECochG responses were also observed but, at the end, returned to baseline (surgery-related deterioration of hearing); Patient #3 – irreversible changes of TT-ECochG and direct CNAP (complete loss of hearing). <br><b>Conclusions:</b> A combination of TT-ECochG and direct CNAP allows for real-time monitoring of auditory function during vestibular schwannoma resection and surgical manipulation which contribute to the risk of hearing loss. Therefore, the surgeon can be instantly informed about changes which could increase the possibility of preserving the patient’s hearing

Interplay between axonal Wnt5-Vang and dendritic Wnt5-Drl/Ryk signaling controls glomerular patterning in the Drosophila antennal lobe

Despite the importance of dendritic targeting in neural circuit assembly, the mechanisms by which it is controlled still remain incompletely understood. We previously showed that in the developing Drosophila antennal lobe, the Wnt5 protein forms a gradient that directs the ~45° rotation of a cluster of projection neuron (PN) dendrites, including the adjacent DA1 and VA1d dendrites. We report here that the Van Gogh (Vang) transmembrane planar cell polarity (PCP) protein is required for the rotation of the DA1/VA1d dendritic pair. Cell type-specific rescue and mosaic analyses showed that Vang functions in the olfactory receptor neurons (ORNs), suggesting a codependence of ORN axonal and PN dendritic targeting. Loss of Vang suppressed the repulsion of the VA1d dendrites by Wnt5, indicating that Wnt5 signals through Vang to direct the rotation of the DA1 and VA1d glomeruli. We observed that the Derailed (Drl)/Ryk atypical receptor tyrosine kinase is also required for the rotation of the DA1/VA1d dendritic pair. Antibody staining showed that Drl/Ryk is much more highly expressed by the DA1 dendrites than the adjacent VA1d dendrites. Mosaic and epistatic analyses showed that Drl/Ryk specifically functions in the DA1 dendrites in which it antagonizes the Wnt5-Vang repulsion and mediates the migration of the DA1 glomerulus towards Wnt5. Thus, the nascent DA1 and VA1d glomeruli appear to exhibit Drl/Ryk-dependent biphasic responses to Wnt5. Our work shows that the final patterning of the fly olfactory map is the result of an interplay between ORN axons and PN dendrites, wherein converging pre- and postsynaptic processes contribute key Wnt5 signaling components, allowing Wnt5 to orient the rotation of nascent synapses through a PCP mechanism.

Molecular dynamics simulations and linear response theories jointly describe biphasic responses of myoglobin relaxation and reveal evolutionarily conserved frequent communicators

In this study, we provide a time-dependent (td-) mechanical model, taking advantage of molecular dynamics (MD) simulations, quasiharmonic analysis of MD trajectories and td-linear response theories (td-LRT) to describe vibrational energy redistribution within the protein matrix. The theoretical description explains the observed biphasic responses of specific residues in myoglobin to CO-photolysis and photoexcitation on heme. The fast responses are found triggered by impulsive forces and propagated mainly by principal modes <40 cm-1. The predicted fast responses for individual atoms are then used to study signal propagation within protein matrix and signals are found to propagate ∼ 8 times faster across helices (4076 m/s) than within the helices, suggesting the importance of tertiary packing in proteins’ sensitivity to external perturbations. We further develop a method to integrate multiple intramolecular signal pathways and discover frequent “communicators”. These communicators are found evolutionarily conserved including those distant from the heme.

On the Nonmonotonic, Hormetic Photoprotective Response of Plants to Stress

Accumulated evidence show that reactive species play a dual role in plants as well, with likely biphasic responses. This suggests that photoprotective mechanisms may also show similar patterns because they are highly related to reactive species. The nonphotochemical quenching (NPQ) is an index of heat dissipation of excitation energy in the antenna system. We present here preliminary evidence from some published studies showing significant biphasic response of NPQ to increasing doses of stress, with U-shaped or inverted U-shaped dose–response relationships, typical of hormesis. This evidence provides a remarkable perspective for designing novel studies where the fate of light energy will be seen through the lens of hormesis.