Intrinsic Membrane Properties Research Articles

Long-term adaptation of prefrontal circuits in a mouse model of NMDAR hypofunction

Pharmacological approaches to induce N-methyl-d-aspartate receptor (NMDAR) hypofunction have been intensively used to understand the aetiology and pathophysiology of schizophrenia. Yet, the precise cellular and molecular mechanisms that relate to brain network dysfunction remain largely unknown. Here, we used a set of complementary approaches to assess the functional network abnormalities present in male mice that underwent a 7-day subchronic phencyclidine (PCP 10 mg/kg, subcutaneously, once daily) treatment. Our data revealed that pharmacological intervention with PCP affected cognitive performance and auditory evoked gamma oscillations in the prefrontal cortex (PFC) mimicking endophenotypes of some schizophrenia patients. We further assessed PFC cellular function and identified altered neuronal intrinsic membrane properties, reduced parvalbumin (PV) immunostaining and diminished inhibition onto L5 PFC pyramidal cells. A decrease in the strength of optogenetically-evoked glutamatergic current at the ventral hippocampus to PFC synapse was also demonstrated, along with a weaker shunt of excitatory transmission by local PFC interneurons. On a macrocircuit level, functional ultrasound measurements indicated compromised functional connectivity within several brain regions particularly involving PFC and frontostriatal circuits. Herein, we reproduced a panel of schizophrenia endophenotypes induced by subchronic PCP application in mice. We further recapitulated electrophysiological signatures associated with schizophrenia and provided an anatomical reference to critical elements in the brain circuitry. Together, our findings contribute to a better understanding of the physiological underpinnings of deficits induced by subchronic NMDAR antagonist regimes and provide a test system for characterization of pharmacological compounds.

Harnessing the Intrinsic Ionic Rectification Properties of Blind‐Hole Nanoporous Anodic Alumina for Osmotic Energy Generation

AbstractThe full potential of blue energy as a sustainable technology for high‐performance energy generation remains elusive. Nanoporous anodic alumina (NAA) is extensively used as a passive structural support to develop a broad variety of ion exchange membranes based on other materials for osmosis‐driven energy generation. However, the intrinsic ionic current rectification (ICR) properties of the inherited hemispherical barrier oxide layer (BOL) closing the bottom tips of NAA's nanopores are overlooked. As‐produced NAA provides new avenues to control ionic transport through its BOL, acting as an ICR model system to study electric current associated with the selective flow of ions across anodic oxides. This study explores the intrinsic capability of NAA membranes for osmotic energy generation. NAA membranes with a working area of 13.4 mm2 can generate a power density yield of ≈2.8×10−4 W m−2 when subjected to a 105‐fold salinity ratio at a pH 3 in CaCl2 electrolyte, achieving a high efficiency of 7%. With better understanding of the mechanism of ion transport on osmotic generation, the intrinsic properties of NAA membranes can be tailor‐engineered to maximize blue energy yield, paving the way for future developments in a scalable technology suited for real‐life applications.

Ndnf Interneuron Excitability Is Spared in a Mouse Model of Dravet Syndrome.

Dravet syndrome (DS) is a neurodevelopmental disorder characterized by epilepsy, developmental delay/intellectual disability, and features of autism spectrum disorder, caused by heterozygous loss-of-function variants in SCN1A encoding the voltage-gated sodium channel α subunit Nav1.1. The dominant model of DS pathogenesis is the "interneuron hypothesis," whereby GABAergic interneurons (INs) express and preferentially rely on Nav1.1-containing sodium channels for action potential (AP) generation. This has been shown for three of the major subclasses of cerebral cortex GABAergic INs: those expressing parvalbumin (PV), somatostatin, and vasoactive intestinal peptide. Here, we define the function of a fourth major subclass of INs expressing neuron-derived neurotrophic factor (Ndnf) in male and female DS (Scn1a+/-) mice. Patch-clamp electrophysiological recordings of Ndnf-INs in brain slices from Scn1a+/â mice and WT controls reveal normal intrinsic membrane properties, properties of AP generation and repetitive firing, and synaptic transmission across development. Immunohistochemistry shows that Nav1.1 is strongly expressed at the axon initial segment (AIS) of PV-expressing INs but is absent at the Ndnf-IN AIS. In vivo two-photon calcium imaging demonstrates that Ndnf-INs in Scn1a+/â mice are recruited similarly to WT controls during arousal. These results suggest that Ndnf-INs are the only major IN subclass that does not prominently rely on Nav1.1 for AP generation and thus retain their excitability in DS. The discovery of a major IN subclass with preserved function in the Scn1a+/â mouse model adds further complexity to the "interneuron hypothesis" and highlights the importance of considering cell-type heterogeneity when investigating mechanisms underlying neurodevelopmental disorders.

Late-spiking retrosplenial cortical neurons are not synchronized with neocortical slow waves in anesthetized mice

Neocortical slow waves are critical for memory consolidation. The retrosplenial cortex is thought to facilitate the slow wave propagation to regions beyond the neocortex. However, it remains unclear which population is responsible for the slow wave propagation. To address this issue, we performed in vivo whole-cell recordings to identify neurons that were synchronous and asynchronous with slow waves. By quantifying their intrinsic membrane properties, we observed that the former exhibited regular spiking, whereas the latter exhibited late spiking. Thus, these two cell types transmit information in different directions between the neocortex and subcortical regions.

Impact of deposited Pt particles on water channel connectivity and proton conductivity in proton exchange membranes: A molecular dynamics study

Deposition of platinum ions in the proton exchange membrane significantly affects the long-term stability and proton transport capacity of the membrane electrode assembly. In this study, the impacts of deposited Pt particles on the intrinsic properties of proton exchange membranes and its mechanisms are investigated using molecular dynamics simulation method. The effect of differently sized Pt particles on water channel connectivity and proton conductivity in proton exchange membranes under dry, normal, and saturated conditions was detailly discussed. The results reveal that Pt particles reduce water channel connectivity at low hydration level while increasing it at normal and high hydration levels. However, the enhancement mechanism is different. Moreover, proton conductivity was evaluated by examining the diffusion of hydronium ions and hydrogen bond dynamics. We found that the proton conduction performance of the membranes at low hydration levels is significantly reduced by Pt particles. We believe this study can promote the design of more robust and efficient proton exchange membranes.

Acute inhibition of acid sensing ion channel 1a after spinal cord injury selectively affects excitatory synaptic transmission, but not intrinsic membrane properties, in deep dorsal horn interneurons.

Following a spinal cord injury (SCI), secondary damage mechanisms are triggered that cause inflammation and cell death. A key component of this secondary damage is a reduction in local blood flow that initiates a well-characterised ischemic cascade. Downstream hypoxia and acidosis activate acid sensing ion channel 1a (ASIC1a) to trigger cell death. We recently showed that administration of a potent venom-derived inhibitor of ASIC1a, Hi1a, leads to tissue sparing and improved functional recovery when delivered up to 8 h after ischemic stroke. Here, we use whole-cell patch-clamp electrophysiology in a spinal cord slice preparation to assess the effect of acute ASIC1a inhibition, via a single dose of Hi1a, on intrinsic membrane properties and excitatory synaptic transmission long-term after a spinal cord hemisection injury. We focus on a population of interneurons (INs) in the deep dorsal horn (DDH) that play a key role in relaying sensory information to downstream motoneurons. DDH INs in mice treated with Hi1a 1 h after a spinal cord hemisection showed no change in active or passive intrinsic membrane properties measured 4 weeks after SCI. DDH INs, however, exhibit significant changes in the kinetics of spontaneous excitatory postsynaptic currents after a single dose of Hi1a, when compared to naive animals (unlike SCI mice). Our data suggest that acute ASIC1a inhibition exerts selective effects on excitatory synaptic transmission in DDH INs after SCI via specific ligand-gated receptor channels, and has no effect on other voltage-activated channels long-term after SCI.

What, if anything, is coincidence detection?

Neural delays and coincidence detection are neural operations posited as key elements in temporal processing, in the auditory system and beyond. Although longstanding physiological evidence for coincidence detectors exists at a phenomenological level, mechanistic examinations have only recently been performed. We review intracellular recordings from two cell types which are traditionally regarded as prototypes of coincidence detectors. Neurons in the medial superior olive (MSO) are sensitive to “coincidences” in action potentials from the ipsi- and contralateral ear, making the neurons sensitive to interaural temporal differences. Octopus cells in the cochlear nucleus are sensitive to “coincidences” of action potentials across inputs tuned to a wide range of frequencies. We found that in both cases, the spike output of neurons does not simply reflect coincidences of input spikes. When inputs vary in strength, their sequence of activation is an important determinant of response strength. Maximal output is not just determined by the maximal number of coincidences, but reflects temporal input structure in interaction with intrinsic (membrane) properties. These observations suggest a simpler mechanism of temporal sensitivity than traditional lag and coincidence proposals.

ST2-Conditioned Medium Fosters Dorsal Horn Cell Excitability and Synaptic Transmission in Cultured Mouse Spinal Cord

Conditioned medium obtained from bone marrow-derived stem cells has been proposed as a novel cell-free therapy in spinal cord injury and neuropathic pain, yet the direct effect on spinal neuron function has never been investigated. Here, we adopted spinal cord organotypic cultures (SCOCs) as an experimental model to probe the effect of ST2 murine mesenchymal stem cells-conditioned medium (ST2-CM) on dorsal horn (DH) neuron functional properties. Three days of SCOC exposure to ST2-CM increased neuronal activity measured by Fos expression, as well as spontaneous or induced firing. We showed that the increase in neuronal excitability was associated with changes in both intrinsic membrane properties and an enhanced excitatory drive. The increased excitability at the single-cell level was substantiated at the network level by detecting synchronous bursts of calcium waves across DH neurons. Altogether, SCOCs represent a viable tool to probe mesenchymal cells' effect on intact neuronal networks. Our findings indicate that ST2-CM enhances neuronal activity and synaptic wiring in the spinal dorsal horn. Our data also support the trophic role of mesenchymal cells CM in maintaining network activity in spinal circuits.Graphical

Electrochemical Science & Engineering Graduate Program at the University of California Irvine

The initiative to create an interdisciplinary program to train PhD (and in parallel terminal ME) graduate students in electrochemistry have been in circulation at University of California Irvine (UCI) since the Fall of 2018. Several “grass-root” meetings of faculty with sustained professional interests in the general interdisciplinary area of electrochemistry and electrochemical engineering involving faculty from UCI School of Physical Sciences (Chemistry and Physics & Astronomy) and Henry Samueli School of Engineering (Chemical & Biomolecular Engineering, Materials Science & Engineering, Mechanical & Aerospace Engineering) have taken place and lead to an internal formal proposal to create the program. This process was additionally catalyzed by the transformation of UCI Advanced Power & Energy Program into UCI Clean Energy Institute, to include National Fuel Cell Research Center and Horiba Institute for Mobility & Connectivity. This initiative was indeed halted for practically three years by the COVID pandemics and is being revisited just now in the Fall of 2022. The campus wide initiative Electrochemical Science & Engineering aims to support building a strong academic discipline to serve as a science and engineering backbone for decarbonization of technology and economy. The general research areas are (listed below) are being supported by a series of graduate classes: Electrochemistry & Electroanalytical Methods (Chemistry); Electrochemical Thermodynamics & ElectrochemicalSystems (MAE); Kinetics of Electrochemical Processes (CBE); Electrochemical Engineering (CBE); Electrochemical Energy Conversion & Storage (CBE) and Solid-State Electrochemistry (MSE) – all of which have been taught in a given, pre-arranged sequence as electives in correspondent departments with an substantially overlapping student audience during 2020/21 and 2021/2022 Academic Years. New technical electives in the areas of Bioelectrochemistry & Bioenergetics, Electrochemical Sensors & Biosensors and Electrochemical Water Treatment Technologies are being prepared for the 2022/223 Academic Year by newly recruited faculty. The lineup of the curriculum and the segmentation of it into specializations will be discussed. We will also address the creation of professional (termina) Master in Engineering (ME) graduate program.Research themes that will be covered by the program are practiced by some 17 faculty at UC: Electrochemical energy technologies, such as fuel cells, electrochemical sensors, electrolyzes, and batteries, use chemical change to produce electricity, or vice versa, and consist of catalytic electrodes and ion-conducting electrolytes. Ion transport between the electrolytes is often limited due to intrinsic properties of (often polymeric) ion-exchange membranes, or low-temperature conductivity of solid-state ionic materials. The next frontier in the science and technology of electrochemical interfacesis exploiting the unique opportunities offered by our emerging ability understand ionic and charge transfer interactions at nanoscale and to tailor both soft and solid-state materials structures to facilitate such interactions including in corrugated and confined structures. Electrocatalytic systems directly utilize electrical energy to perform redox reactions. The latter is essential to most chemical bond forming/breaking events and in energy storage and utilization reactions. Molecular electrocatalysis effort is focused on designing molecules with tailored active sites, predicted by computational chemistry, in order to achieve optimal energies in abundant metals. This further extends to bioelectrocatalysis by proteins and bioelectrochemistry of cells.

Graphyne-based membrane as a promising candidate for Li-Battery electrodes protection: Insight from atomistic simulations

All-solid electrolytes could lead to a technological breakthrough in the performance of all-solid-state batteries when combined with a lithium-metal anode. However, the use of a lithium-metal anode presents several challenges, such as dendrite growth, interface electrochemical stability, formation and propagation of cracks, and delamination of the electrode/electrolyte interfaces. This work aims to explore the effectiveness of using newly synthesized 2D graphyne-based membranes (namely graphyne, graphdiyne, and graphtriyne) for electrode protection in a solid polymer electrolyte battery through first-principle calculations, nudged elastic band method, and classical molecular dynamics simulation. Specifically, we aim to investigate the effectiveness of these membranes in mitigating the aforementioned challenges. A high external electric field of up to 0.5 V/Å, 0.75 V/Å, and 1 V/Å was applied to accelerate the ions diffusion process. The adsorption energies, charge transfer, and in-plane/out-plane diffusion of single lithium on graphyne-based surfaces were investigated. Afterward, we calculated and compared the Li+ permeability, the electrolyte molecules’ rejection efficiency, and the intrinsic properties of graphyne-based nanoporous membranes. Our findings show that both graphyne and graphdiyne surfaces effectively permit Li+ intercalation while preventing other electrolyte molecules from reaching the electrodes.

Altered flexor carpi radialis motor axon excitability properties after cerebrovascular stroke.

Spinal motoneurons may become hyperexcitable after a stroke. Knowledge about motoneuron hyperexcitability remains clinically important as it may contribute to a number of phenomena including spasticity, flexion synergies, and abnormal limb postures. Hyperexcitability seems to occur more often in muscles that flex the wrist and fingers (forearm flexors) compared to other upper limb muscles. The cause of hyperexcitability remains uncertain but may involve plastic changes in motoneurons and their axons. To characterize intrinsic membrane properties of flexor carpi radialis (FCR) motor axons after stroke using nerve excitability testing. Nerve excitability testing using threshold tracking techniques was applied to characterize FCR motor axon properties in persons who suffered a first-time unilateral cortical/subcortical stroke 23 to 308 days earlier. The median nerve was stimulated at the elbow bilaterally in 16 male stroke subjects (51.4 ± 2.9 y) with compound muscle action potentials recorded from the FCR. Nineteen age-matched males (52.7 ± 2.4 y) were also tested to serve as controls. Axon parameters after stroke were consistent with bilateral hyperpolarization of the resting potential. Nonparetic and paretic side axons were modeled by a 2.6-fold increase in pump currents (IPumpNI) together with an increase (38%-33%) in internodal leak conductance (GLkI) and a decrease (23%-29%) in internodal H conductance (Ih) relative to control axons. A decrease (14%) in Na+ channel inactivation rate (Aah) was also needed to fit the paretic axon recovery cycle. "Fanning out" of threshold electrotonus and the resting I/V slope (stroke limbs combined) correlated with blood potassium [K+] (R = -0.61 to 0.62, p< 0.01) and disability (R = -0.58 to 0.55, p < 0.05), but not with spasticity, grip strength, or maximal FCR activity. In contrast to our expectations, FCR axons were not hyperexcitable after stroke. Rather, FCR axons were found to be hyperpolarized bilaterally post stroke, and this was associated with disability and [K+]. Reduced FCR axon excitability may represent a kind of bilateral trans-synaptic homeostatic mechanism that acts to minimize motoneuron hyperexcitability.

Regulation of molecular transport in polymer membranes with voltage-controlled pore size at the angstrom scale

Polymer membranes have been used extensively for Angstrom-scale separation of solutes and molecules. However, the pore size of most polymer membranes has been considered an intrinsic membrane property that cannot be adjusted in operation by applied stimuli. In this work, we show that the pore size of an electrically conductive polyamide membrane can be modulated by an applied voltage in the presence of electrolyte via a mechanism called electrically induced osmotic swelling. Under applied voltage, the highly charged polyamide layer concentrates counter ions in the polymer network via Donnan equilibrium and creates a sizeable osmotic pressure to enlarge the free volume and the effective pore size. The relation between membrane potential and pore size can be quantitatively described using the extended Flory-Rehner theory with Donnan equilibrium. The ability to regulate pore size via applied voltage enables operando modulation of precise molecular separation in-situ. This study demonstrates the amazing capability of electro-regulation of membrane pore size at the Angstrom scale and unveils an important but previously overlooked mechanism of membrane-water-solute interactions.

Persistent inflammation selectively activates opioid-sensitive phasic-firing neurons within the vlPAG.

The ventrolateral periaqueductal gray (vlPAG) is a key brain area within the descending pain modulatory pathway and an important target for opioid-induced analgesia. The vlPAG contains heterogeneous neurons with respect to neurotransmitter content, receptor and channel expression, and in vivo response to noxious stimuli. This study characterizes intrinsic membrane properties of vlPAG neurons to identify neuron types that respond to inflammation and determine whether the pain-responsive neurons are inhibited by opioids. Surveying 382 neurons identified four neuron types with distinct intrinsic firing patterns: Phasic (48%), Tonic (33%), Onset (10%), and Random (9%). Mu-opioid receptor (MOR) expression was determined by the ability of a selective MOR agonist (DAMGO) to activate G protein-coupled inwardly rectifying potassium channel (GIRK) currents. Opioid-sensitive neurons were observed within each neuron type. Opioid sensitivity did not correlate with other intrinsic firing features, including low-threshold spiking that has been previously proposed to identify opioid-sensitive GABAergic neurons in the vlPAG of mice. Complete Freund's adjuvant (CFA)-induced acute inflammation (2 h) had no effect on vlPAG neuron firing patterns. However, persistent inflammation (5-7 days) selectively activated Phasic neurons through a significant reduction in their firing threshold. Opioid-sensitive neurons were strongly activated compared with the opioid-insensitive Phasic neurons. Overall, this study provides a framework to further identify neurons activated by persistent inflammation so that they may be targeted for future pain therapies.NEW & NOTEWORTHY Intrinsic firing properties define four distinct vlPAG neuron populations, and a subset of each population expresses MORs coupled to GIRK channels. Persistent, but not acute, inflammation selectively activates opioid-sensitive Phasic vlPAG neurons. Although the vlPAG is known to contribute to the descending inhibition of pain, the activation of a single physiologically defined neuron type in the presence of persistent inflammation represents a mechanism by which the vlPAG participates in descending facilitation of pain.

Enveloped viruses pseudotyped with mammalian myogenic cell fusogens target skeletal muscle for gene delivery

Entry of enveloped viruses into cells is mediated by viral fusogenic proteins that drive membrane rearrangements needed for fusion between viral and target membranes. Skeletal muscle development also requires membrane fusion events between progenitor cells to form multinucleated myofibers. Myomaker and Myomerger are muscle-specific cell fusogens but do not structurally or functionally resemble classical viral fusogens. We asked whether the muscle fusogens could functionally substitute for viral fusogens, despite their structural distinctiveness, and fuse viruses to cells. We report that engineering of Myomaker and Myomerger on the membrane of enveloped viruses leads to specific transduction of skeletal muscle. We also demonstrate that locally and systemically injected virions pseudotyped with the muscle fusogens can deliver μDystrophin to skeletal muscle of a mouse model of Duchenne muscular dystrophy and alleviate pathology. Through harnessing the intrinsic properties of myogenic membranes, we establish a platform for delivery of therapeutic material to skeletal muscle.

Aberrant somatic calcium channel function in cNurr1 and LRRK2-G2019S mice

In Parkinson’s disease (PD), axons of dopaminergic (DA) neurons in the substantia nigra pars compacta (SNc) degenerate before their cell bodies. Calcium influx during pacemaker firing might contribute to neuronal loss, but it is not known if dysfunctions of voltage-gated calcium channels (VGCCs) occur in DA neurons somata and axon terminals. We investigated T-type and L-type VGCCs in SNc-DA neurons of two mouse models of PD: mice with a deletion of the Nurr1 gene in DA neurons from an adult age (cNurr1 mice), and mice bearing the G2019S mutation in the gene coding for LRRK2 (G2019S mice). Adult cNurr1 mice displayed motor and DA deficits, while middle-aged G2019S mice did not. The number and morphology of SNc-DA neurons, most of their intrinsic membrane properties and pacemaker firing were unaltered in cNurr1 and G2019S mice compared to their control and wild-type littermates. L-type VGCCs contributed to the pacemaker firing of SNc-DA neurons in G2019S mice, but not in control, wild-type, and cNurr1 mice. In cNurr1 mice, but not G2019S mice, the contribution of T-type VGCCs to the pacemaker firing of SNc-DA neurons was reduced, and somatic dopamine-D2 autoreceptors desensitized more. Altered contribution of L-type and T-type VGCCs to the pacemaker firing was not observed in the presence of a LRRK2 kinase inhibitor in G2019S mice, and in the presence of a flavonoid with antioxidant activity in G2019S and cNurr1 mice. The role of L-type and T-type VGCCs in controlling dopamine release from axon terminals in the striatum was unaltered in cNurr1 and G2019S mice. Our findings uncover opposite changes, linked to oxidative stress, in the function of two VGCCs in DA neurons somata, but not axon terminals, in two different experimental PD models.

Evaluation of Surface Properties and Separation Performance of NF and RO Membranes for Phthalates Removal

Many studies indicated that phthalates, a common plasticizer, lurk silently in water bodies and can potentially harm living organisms. Therefore, removing phthalates from water sources prior to consumption is crucial. This study aims to evaluate the performance of several commercial nanofiltrations (NF) (i.e., NF3 and Duracid) and reverse osmosis (RO) membranes (i.e., SW30XLE and BW30) in removing phthalates from simulated solutions and further correlate the intrinsic properties of membranes (e.g., surface chemistry, morphology, and hydrophilicity) with the phthalates removal. Two types of phthalates, i.e., dibutyl phthalate (DBP) and butyl benzyl phthalate (BBP), were used in this work, and the effects of pH (ranging from 3 to 10) on the membrane performance were studied. The experimental findings showed that the NF3 membrane could yield the best DBP (92.5-98.8%) and BBP rejection (88.7-91.7%) regardless of pH, and these excellent results are in good agreement with the surface properties of the membrane, i.e., low water contact angle (hydrophilicity) and appropriate pore size. Moreover, the NF3 membrane with a lower polyamide cross-linking degree also exhibited significantly higher water flux compared to the RO membranes. Further investigation indicated that the surface of the NF3 membrane was severely covered by foulants after 4-h filtration of DBP solution compared to the BBP solution. This could be attributed to the high concentration of DBP presented in the feed solution owing to its high-water solubility (13 ppm) compared to BBP (2.69 ppm). Further research is still needed to study the effect of other compounds (e.g., dissolved ions and organic/inorganic matters that might be present in water) on the performance of membranes in removing phthalates.

Developmental changes in electrophysiological properties of auditory cortical neurons in the Cntnap2 knockout rat.

Disruptions in the CNTNAP2 gene are known to cause language impairments and symptoms associated with autism spectrum disorder (ASD). Importantly, knocking out this gene in rodents results in ASD-like symptoms that include auditory processing deficits. This study used in vitro patch-clamp electrophysiology to examine developmental alterations in auditory cortex pyramidal neurons of Cntnap2-/- rats, hypothesizing that CNTNAP2 is essential for maintaining intrinsic neuronal properties and synaptic wiring in the developing auditory cortex. Whole-cell patch-clamp recordings were conducted in wildtype and Cntnap2-/- littermates at 3 postnatal age ranges (P8-12, P18-21, and P70-90). Consistent changes across age were seen in all measures of intrinsic membrane properties and spontaneous synaptic input. Intrinsic cell properties such as action potential half widths, rheobase, and action-potential firing frequencies were different between wildtype and Cntnap2-/- rats predominantly during the juvenile stage (P18-21), whereas adult Cntnap2-/- rats showed higher frequencies of spontaneous and mini excitatory post-synaptic currents (sEPSC; mEPSC), with lower sEPSC amplitudes. These results indicate that intrinsic cell properties are altered in Cntnap2-/- during the juvenile age, leading to a hyperexcitable phenotype during this stage of synaptic remodeling and refinement. While intrinsic properties eventually normalize by reaching adulthood, changes in synaptic input, potentially caused by the differences in intrinsic membrane properties, seem to manifest in the adult age and are presumably responsible for the hyperreactive behavioral phenotype. In conjunction with a previous study, the present results also indicate a large influence of breeding scheme, i.e., pre- or postnatal environment, on the impact of Cntnap2 on cellular physiology.

A predictive procedure to model gas transport and intrinsic properties of rubbery polymeric membranes using equilibrium thermodynamics and free volume theory

A predictive procedure to model gas transport and intrinsic properties of rubbery polymeric membranes using equilibrium thermodynamics and free volume theory

Electrophysiologically distinct bed nucleus of the stria terminalis projections to the ventral tegmental area in mice.

The bed nucleus of the stria terminalis (BNST) is a highly heterogeneous limbic forebrain structure that serves as a relay connecting autonomic, neuroendocrine and behavioral function. It can be divided into over 16 individual subregions with distinct neuronal subpopulations based on receptors, transmitters, and neuropeptides. Specifically, the BNST projection to the ventral tegmental area (VTA), the dopamine hub of the brain, has been shown to have a crucial role in the stress response. However, in mice there is a lack of unbiased data on the functional diversity of this sub-population which serves as an upstream input to the VTA. The dopaminergic neurons in the VTA modify their ion channel activity and intrinsic membrane properties to adapt to stress in part from inputs from BNST projections. Therefore, we aimed to perform a multi-component characterization of the functional diversity of the BNST-VTA pathway. We studied the passive and active electrophysiological properties of virally identified population of BNST neurons that project to the VTA. We used a comprehensive series of in vitro recordings of electrophysiological variables and performed hierarchical clustering to determine the functional diversity of the projection neurons in the BNST-VTA pathway. Our study revealed four subpopulations in the BNST-VTA pathway, all of which differ in their activation profiles and likely have distinct inputs and function in the VTA. Our results will help resolve the discord in interpretation of the various roles of this electrophysiologically diverse projection and builds a foundation for understanding how the different neuronal types integrate signals.

Transient effects of junk food on NAc core MSN excitability and glutamatergic transmission in obesity-prone female rats.

The nucleus accumbens (NAc) plays critical roles in eating and food seeking in rodents and humans. Diets high in fats and sugars ("junk food") produce persistent increases in NAc function in male obesity-prone rats. This study examines effects of junk food and junkfood deprivation on NAc core medium spiny neuron (MSN) excitability and glutamate transmission in females. Obesity-prone female rats were given access to ad libitum junkfood for 10 days, and recordings were made from MSNs in the NAc core immediately or after a short (27-72 hours) or long (14-16 days) junk food deprivation period in which rats were returned to ad libitum standard chow. Controls remained on chow throughout. Whole-cell slice electrophysiology was used to examine MSN intrinsic membrane and firing properties and glutamatergic transmission. The study found that intrinsic excitability was reduced, whereas glutamatergic transmission was enhanced, after the short, but not long, junk food deprivation period. A brief junk food deprivation period was necessary for increases in NAc calcium-permeable-AMPA receptor transmission and spontaneous excitatory postsynaptic current (sEPSC) frequency, but not for increases in sEPSC amplitude. This study reveals that females are protected from long-lasting effects of sugary fatty foods on MSN neuronal function and provides evidence for sex-specific effects on plasticity in brain centers that influence food-seeking and feeding behavior.