Non-uniform distribution of dendritic nonlinearities differentially engages thalamostriatal and corticostriatal inputs onto cholinergic interneurons

The tonic activity of striatal cholinergic interneurons (CINs) is modified differentially by their afferent inputs. Although their unitary synaptic currents are identical, cortical inputs onto distal dendrites only weakly entrain CINs, whereas proximal thalamic inputs trigger abrupt pauses in discharge in response to salient external stimuli. To test whether the dendritic expression of the active conductances that drive autonomous discharge contribute to the CINs' capacity to dissociate cortical from thalamic inputs, we used an optogenetics-based method to quantify dendritic excitability. We found that the persistent sodium (NaP) current gave rise to dendritic boosting and that the hyperpolarization-activated cyclic nucleotide-gated (HCN) current gave rise to a subhertz membrane resonance. This resonance may underlie our novel finding of an association between CIN pauses and internally-generated slow wave events in sleeping non-human primates. Moreover, our method indicated that dendritic NaP and HCN currents were preferentially expressed in proximal dendrites. We validated this non-uniform distribution with two-photon imaging of dendritic back-propagating action potentials, and by demonstrating boosting of thalamic, but not cortical, inputs by NaP currents. Thus, the localization of active dendritic conductances in CIN dendrites mirrors the spatial distribution of afferent terminals and may promote their differential responses to thalamic vs. cortical inputs.

Membrane Resonance in Pyramidal and GABAergic Neurons of the Mouse Perirhinal Cortex

The perirhinal cortex (PRC) is a polymodal associative region of the temporal lobe that works as a gateway between cortical areas and hippocampus. In recent years, an increasing interest arose in the role played by the PRC in learning and memory processes, such as object recognition memory, in contrast with certain forms of hippocampus-dependent spatial and episodic memory. The integrative properties of the PRC should provide all necessary resources to select and enhance the information to be propagated to and from the hippocampus. Among these properties, we explore in this paper the ability of the PRC neurons to amplify the output voltage to current input at selected frequencies, known as membrane resonance. Within cerebral circuits the resonance of a neuron operates as a filter toward inputs signals at certain frequencies to coordinate network activity in the brain by affecting the rate of neuronal firing and the precision of spike timing. Furthermore, the ability of the PRC neurons to resonate could have a fundamental role in generating subthreshold oscillations and in the selection of cortical inputs directed to the hippocampus. Here, performing whole-cell patch-clamp recordings from perirhinal pyramidal neurons and GABAergic interneurons of GAD67-GFP+ mice, we found, for the first time, that the majority of PRC neurons are resonant at their resting potential, with a resonance frequency of 0.5–1.5 Hz at 23°C and of 1.5–2.8 Hz at 36°C. In the presence of ZD7288 (blocker of HCN channels) resonance was abolished in both pyramidal neurons and interneurons, suggesting that Ih current is critically involved in resonance generation. Otherwise, application of TTx (voltage-dependent Na+ channel blocker) attenuates the resonance in pyramidal neurons but not in interneurons, suggesting that only in pyramidal neurons the persistent sodium current has an amplifying effect. These experimental results have also been confirmed by a computational model. From a functional point of view, the resonance in the PRC would affect the reverberating activity between neocortex and hippocampus, especially during slow wave sleep, and could be involved in the redistribution and strengthening of memory representation in cortical regions.

A role for tectorial membrane mechanics in activating the cochlear amplifier

The mechanical and electrical responses of the mammalian cochlea to acoustic stimuli are nonlinear and highly tuned in frequency. This is due to the electromechanical properties of cochlear outer hair cells (OHCs). At each location along the cochlear spiral, the OHCs mediate an active process in which the sensory tissue motion is enhanced at frequencies close to the most sensitive frequency (called the characteristic frequency, CF). Previous experimental results showed an approximate 0.3 cycle phase shift in the OHC-generated extracellular voltage relative the basilar membrane displacement, which was initiated at a frequency approximately one-half octave lower than the CF. Findings in the present paper reinforce that result. This shift is significant because it brings the phase of the OHC-derived electromotile force near to that of the basilar membrane velocity at frequencies above the shift, thereby enabling the transfer of electrical to mechanical power at the basilar membrane. In order to seek a candidate physical mechanism for this phenomenon, we used a comprehensive electromechanical mathematical model of the cochlear response to sound. The model predicts the phase shift in the extracellular voltage referenced to the basilar membrane at a frequency approximately one-half octave below CF, in accordance with the experimental data. In the model, this feature arises from a minimum in the radial impedance of the tectorial membrane and its limbal attachment. These experimental and theoretical results are consistent with the hypothesis that a tectorial membrane resonance introduces the correct phasing between mechanical and electrical responses for power generation, effectively turning on the cochlear amplifier.

A Mechanism of Real-Time Noise Modulation in Neurons

Uncertainties pose an ongoing challenge for information processing in the nervous system. It is not entirely clear how neurons maintain dynamic stability of information, encoded in the temporal features of spike trains, notwithstanding stochastic influences. Here we examined the contribution of subclasses of membrane sodium currents in real-time noise modulation in sensory neurons. Fast sodium (Na+) currents are essential for spike generation, and a persistent Na+ current can entrain preferred input frequencies via membrane resonance. Using mathematical modeling, theory and experiments, we show that a resurgent Na+ current can stabilize the temporal features of burst discharge and confer noise tolerance. These novel insights reckon the role of biophysical properties of Na+ currents beyond mere spike generation. Instead, these mechanisms might be how neurons perform real-time signal processing to maintain order and entropy in neural discharge. Our model analysis further predicts a negative feedback loop in the molecular machinery of an underlying Nav1.6-type Na+ channel gating considered in this study.

The ionic mechanism of membrane potential oscillations and membrane resonance in striatal LTS interneurons

Striatal low-threshold spiking (LTS) interneurons spontaneously transition to a depolarized, oscillating state similar to that seen after sodium channels are blocked. In the depolarized state, whether spontaneous or induced by sodium channel blockade, the neurons express a 3- to 7-Hz oscillation and membrane impedance resonance in the same frequency range. The membrane potential oscillation and membrane resonance are expressed in the same voltage range (greater than −40 mV). We identified and recorded from LTS interneurons in striatal slices from a mouse that expressed green fluorescent protein under the control of the neuropeptide Y promoter. The membrane potential oscillation depended on voltage-gated calcium channels. Antagonism of L-type calcium currents (CaV1) reduced the amplitude of the oscillation, whereas blockade of N-type calcium currents (CaV2.2) reduced the frequency. Both calcium sources activate a calcium-activated chloride current (CaCC), the blockade of which abolished the oscillation. The blocking of any of these three channels abolished the membrane resonance. Immunohistochemical staining indicated anoctamin 2 (ANO2), and not ANO1, as the CaCC source. Biophysical modeling showed that CaV1, CaV2.2, and ANO2 are sufficient to generate a membrane potential oscillation and membrane resonance, similar to that in LTS interneurons. LTS interneurons exhibit a membrane potential oscillation and membrane resonance that are both generated by CaV1 and CaV2.2 activating ANO2. They can spontaneously enter a state in which the membrane potential oscillation dominates the physiological properties of the neuron.

Theoretical and Experimental Analysis of Active Valve Pumping for High Flow Rate Applications

A new valve-only micropump structure for gas applications is proposed consisting of electrostatically actuated checkerboard microvalves with dual cavities. The valve-only multistage peristaltic design minimizes complexity and footprint of the device, which allows operation at high frequency, better sealing and efficient operation. A previously developed reduced order model is used to design and analyze the performance of the system. In this paper the effect of the cavity height on the performance and stability of this system is explored. The fabricated micropump produced a flow rate of 140 μl/min at 1 kHz operation despite the cavity and membrane resonance being > 20 kHz. Four micropumps having cavity heights of 45, 60, 90 and 120 μm are explored in the modeling efforts using sinusoidal waveforms. It is found that an optimum cavity height exists which maximizes pump performance. Decreasing the cavity height below this value increases acoustic pressure damping, which in turn increases instability of the system.

Modeling of Perforated Screens or Membrane Using Rigid Frame Porous Models Combined with Thin Membrane Resonance Sound Absorbing Theory

The sound absorption ability of screen or perforated membrane is studied based on rigid frame porous models combined with thin membrane resonance sound absorbing theory in this paper. Results show that the sound absorption of screen or perforated membrane is better considering the role of membrane than using the rigid frame porous models when the mass density of screen or perforated membrane is smaller. The rigid frame porous model is very accuracy to model the sound absorption ability of screen or perforated membrane when the mass density of membrane is greater. The parameter studies present that the sound absorption peaks move toward low frequency region with the increasing of the depth of air-back cavity, mass density and thickness of screens or perforated membrane and moves toward high frequency region with the increasing of the perforation and perforated radius of screens or perforated membrane when other parameters keep invariant.