Dorsal peduncular cortex activity modulates affective behavior and fear extinction in mice.

The medial prefrontal cortex (mPFC) is critical to cognitive and emotional function and underlies many neuropsychiatric disorders, including mood, fear and anxiety disorders. In rodents, disruption of mPFC activity affects anxiety- and depression-like behavior, with specialized contributions from its subdivisions. The rodent mPFC is divided into the dorsomedial prefrontal cortex (dmPFC), spanning the anterior cingulate cortex (ACC) and dorsal prelimbic cortex (PL), and the ventromedial prefrontal cortex (vmPFC), which includes the ventral PL, infralimbic cortex (IL), and in some studies the dorsal peduncular cortex (DP) and dorsal tenia tecta (DTT). The DP/DTT have recently been implicated in the regulation of stress-induced sympathetic responses via projections to the hypothalamus. While many studies implicate the PL and IL in anxiety-, depression-like and fear behavior, the contribution of the DP/DTT to affective and emotional behavior remains unknown. Here, we used chemogenetics and optogenetics to bidirectionally modulate DP/DTT activity and examine its effects on affective behaviors, fear and stress responses in C57BL/6J mice. Acute chemogenetic activation of DP/DTT significantly increased anxiety-like behavior in the open field and elevated plus maze tests, as well as passive coping in the tail suspension test. DP/DTT activation also led to an increase in serum corticosterone levels and facilitated auditory fear extinction learning and retrieval. Activation of DP/DTT projections to the dorsomedial hypothalamus (DMH) acutely decreased freezing at baseline and during extinction learning, but did not alter affective behavior. These findings point to the DP/DTT as a new regulator of affective behavior and fear extinction in mice.

Do housing-induced changes in brain activity cause stereotypic behaviours in laboratory mice?

Abnormal repetitive stereotypic behaviours (SBs) (e.g. pacing, body-rocking) are common in animals with poor welfare (e.g. socially isolated/in barren housing). But how (or even whether) poor housing alters animals' brains to induce SBs remains uncertain. To date, there is little evidence for environmental effects on the brain that also correlate with individual SB performance. Using female mice from two strains (SB-prone DBA/2s; SB-resistant C57/BL/6s), displaying two forms of SB (route-tracing; bar-mouthing), we investigated how housing (conventional laboratory conditions vs. well-resourced 'enriched' cages) affects long-term neuronal activity as assessed via cytochrome oxidase histochemistry in 13 regions of interest (across cortex, striatum, basal ganglia and thalamus). Conventional housing reduced activity in the cortex and striatum. However, DBA mice had no cortical or striatal differences from C57 mice (just greater basal ganglia output activity, independent of housing). Neural correlates for individual levels of bar-mouthing (positive correlations in the substantia nigra and thalamus) were also independent of housing; while route-tracing levels had no clear neural correlates at all. Thus conventional laboratory housing can suppress cortico-striatal activity, but such changes are unrelated to SB (since not mirrored by congruent individual and strain differences). Furthermore, the neural correlates of SB at individual and strain levels seem to reflect underlying predispositions, not housing-mediated changes. To aid further work, hypothesis-generating model fit analyses highlighted this unexplained housing effect, and also suggested several regions of interest across cortex, striatum, thalamus and substantia nigra for future investigation (ideally with improved power to reduce risks of Type II error).

Brain-Generated 17ß-Estradiol Modulates Long-Term Synaptic Plasticity in the Primary Auditory Cortex of Adult Male Rats.

Neuron-derived 17ß-estradiol (E2) alters synaptic transmission and plasticity in brain regions with endocrine and non-endocrine functions. Investigations into a modulatory role of E2 in synaptic activity and plasticity have mainly focused on the rodent hippocampal formation. In songbirds, E2 is synthesized by auditory forebrain neurons and promotes auditory signal processing and memory for salient acoustic stimuli; however, the modulatory effects of E2 on memory-related synaptic plasticity mechanisms have not been directly examined in the auditory forebrain. We investigated the effects of bidirectional E2 manipulations on synaptic transmission and long-term potentiation (LTP) in the rat primary auditory cortex (A1). Immunohistochemistry revealed widespread neuronal expression of the E2 biosynthetic enzyme aromatase in multiple regions of the rat sensory and association neocortex, including A1. In A1, E2 application reduced the threshold for in vivo LTP induction at layer IV synapses, whereas pharmacological suppression of E2 production by aromatase inhibition abolished LTP induction at layer II/III synapses. In acute A1 slices, glutamate and γ-aminobutyric acid (GABA) receptor-mediated currents were sensitive to E2 manipulations in a layer-specific manner. These findings demonstrate that locally synthesized E2 modulates synaptic transmission and plasticity in A1 and suggest potential mechanisms by which E2 contributes to auditory signal processing and memory.

Developmental age and biological sex influence muscarinic receptor function and neuron morphology within layer VI of the medial prefrontal cortex.

Acetylcholine (ACh) neurotransmission within the medial prefrontal cortex (mPFC) plays an important modulatory role to support mPFC-dependent cognitive functions. This role is mediated by ACh activation of its nicotinic (nAChR) and muscarinic (mAChR) classes of receptors, which are both present on mPFC layer VI pyramidal neurons. While the expression and function of nAChRs have been characterized thoroughly for rodent mPFC layer VI neurons during postnatal development, mAChRs have not been characterized in detail. We employed whole-cell electrophysiology with biocytin filling to demonstrate that mAChR function is greater during the juvenile period of development than in adulthood for both sexes. Pharmacological experiments suggest that each of the M1, M2, and M3 mAChR subtypes contributes to ACh responses in these neurons in a sex-dependent manner. Analysis of dendrite morphology identified effects of age more often in males, as the amount of dendrite matter was greatest during the juvenile period. Interestingly, a number of positive correlations were identified between the magnitude of ACh/mAChR responses and dendrite morphology in juvenile mice that were not present in adulthood. To our knowledge, this work describes the first detailed characterization of mAChR function and its correlation with neuron morphology within layer VI of the mPFC.

Thermoelectric properties of GaN with carrier concentration modulation: an experimental and theoretical investigation.

The present work investigates the less explored thermoelectric properties of the n-type GaN semiconductor by combining both experimental and computational tools. The Seebeck coefficients of GaN epitaxial thin films were experimentally measured in the wide temperature range from 77 K to 650 K in steps of ∼10 K covering both low and high-temperature regimes as a function of the carrier concentration (2 × 1016, 2 × 1017, 4 × 1017 and 8 × 1017 cm-3). The measured Seebeck coefficient at room temperature was found to be highest (-374 µV K-1) at the lowest concentration of 4 × 1016 cm-3, and decreases in magnitude monotonically (-327.6 µV K-1, -295 µV K-1, -246 µV K-1 for 2 × 1017, 4 × 1017, 8 × 1017 cm-3, respectively) as the sample carrier concentration increases. The Seebeck coefficient remains negative in the entire temperature range under study indicating that electrons are the dominant carriers. To understand the temperature-dependent behaviour, we also carried out the electronic structure and transport coefficient calculations using the Tran-Blaha modified Becke-Johnson (TB-mBJ) potential and semiclassical Boltzmann transport theory implemented in WIEN2k and BoltzTraP code, respectively. The experimentally observed carrier concentrations were used in the calculations. The estimated results obtained under constant relaxation time approximations provide a very good agreement between the theoretical and experimental data of Seebeck coefficients in the temperature range from 260 to 625 K.

BiRWDDA: A Novel Drug Repositioning Method Based on Multisimilarity Fusion.

The explosive growth of large-scale biological data enables network-based drug repositioning to be an important way of drug discovery, which can reduce the time and cost of drug discovery efficiently. Many existing approaches always construct drug-disease association network only based on some similarity measuring data for drug or disease, which ignore the impacts of different similarity measuring on predicting performance. In this study, we develop a new computational approach named BiRWDDA, which fused multiple similarity measures and bi-random walk to discover potential associations between drugs and diseases. First, multiple drug-drug similarity and disease-disease similarity are measured. Next, the information entropy of similarities measured based on different data are calculated to select proper similarities of drugs and diseases. Subsequently, improved drug-drug similarity and disease-disease similarity can be obtained by fusing similarities selected. Then, a logistic function is adopted to adjust the improved drug similarity and disease similarity. What is more, a heterogeneous network can be conducted by connecting the drug similarity network and the disease similarity network through known drug-disease associations. Finally, a bi-random walk algorithm is implemented on the heterogeneous network to predict potential drug-disease associations. Experimental results demonstrate that BiRWDDA outperforms the other state-of-the-art methods with average AUC of 0.930. Case studies for five selected drugs further verify the favorable prediction performance.

The Neural Dynamics of Facial Identity Processing: Insights from EEG-Based Pattern Analysis and Image Reconstruction.

Uncovering the neural dynamics of facial identity processing along with its representational basis outlines a major endeavor in the study of visual processing. To this end, here, we record human electroencephalography (EEG) data associated with viewing face stimuli; then, we exploit spatiotemporal EEG information to determine the neural correlates of facial identity representations and to reconstruct the appearance of the corresponding stimuli. Our findings indicate that multiple temporal intervals support: facial identity classification, face space estimation, visual feature extraction and image reconstruction. In particular, we note that both classification and reconstruction accuracy peak in the proximity of the N170 component. Further, aggregate data from a larger interval (50-650 ms after stimulus onset) support robust reconstruction results, consistent with the availability of distinct visual information over time. Thus, theoretically, our findings shed light on the time course of face processing while, methodologically, they demonstrate the feasibility of EEG-based image reconstruction.

Fabrication of setup for high temperature thermal conductivity measurement.

In this work, we report the fabrication of an experimental setup for high temperature thermal conductivity (κ) measurement. It can characterize samples with various dimensions and shapes. Steady state based axial heat flow technique is used for κ measurement. Heat loss is measured using parallel thermal conductance technique. Simple design, lightweight, and small size sample holder is developed by using a thin heater and limited components. Low heat loss value is achieved by using very low thermal conductive insulator block with small cross-sectional area. Power delivered to the heater is measured accurately by using 4-wire technique and for this, the heater is developed with 4 wires. This setup is validated by using Bi0.36Sb1.45Te3, polycrystalline bismuth, gadolinium, and alumina samples. The data obtained for these samples are found to be in good agreement with the reported data. The maximum deviation of 6% in the value κ is observed. This maximum deviation is observed with the gadolinium sample. We also report the thermal conductivity of polycrystalline tellurium from 320 K to 550 K and the nonmonotonous behavior of κ with temperature is observed.