Anatomical analyses of collateral prefrontal cortex projections to the basolateral amygdala and the nucleus accumbens core in rats.

The basolateral amygdala (BLA) and the nucleus accumbens core (NAcc) share some similar behavioral functions, such as associative learning, Pavlovian to instrumental transfer, and choice behavior. However, their prefrontal anatomical inputs have not been well characterized before, especially the collateral projections. In this study, we analyzed the distribution and collateralization of projections to the BLA and the NAcc from the prefrontal cortices (PFC), including the prelimbic (PL) and the infralimbic (IL) divisions of the medial prefrontal cortex (mPFC) and the subregions of the orbitofrontal cortex (OFC), such as the medial OFC (MO), the lateral OFC (LO), and the ventral OFC (VO). Double retrograde tracing approach was used, in which Cholera toxin subunit B conjugated with the Alexa Fluor 488 (CTB-AF488) or Alexa Fluor 594 (CTB-AF594) were unilaterally injected into the BLA and the NAcc, respectively, in male Long-Evans rats (n = 6). Among the sampled neurons, prefrontal projection to the BLA or the NAcc is more robust on the ipsilateral side, and more robust from the PL, the IL, and the MO compared to from the LO and the VO. The majority of the projections from the PFC to the BLA and/or the NAcc are confined in deep layer. In addition, for each of the prefrontal areas, about 15-25% BLA-projecting neurons send collateral projections to the NAcc, and vice versa. In conclusion, our data suggested that prefrontal control over the BLA and the NAcc is not entirely independent. The functional importance of the collateral projections awaits further examination.

Inactivation of medial or lateral orbitofrontal cortex during fear extinction did not interfere with fear renewal.

Hyperactive orbitofrontal cortical activation is commonly seen in patients of obsessive-compulsive disorder (OCD). Previous studies from our laboratory showed that for rats with aberrant activation of the orbitofrontal cortex (OFC) during the extinction phase, they were unable to use contexts as the reference for proper retrieval of fear memory during renewal test. This result supported the phenomenon that many OCD patients show poor regulation of fear-related behavior. Since there are robust anatomical connections of the OFC with the fear-circuit, we aim to further examine whether the OFC is actively engaged in fear regulation under normal circumstances. In this study, the lateral or medial OFC was inactivated during the extinction phase using the ABA fear renewal procedure. We found that these animals showed intact fear renewal during retrieval test with their freezing levels equivalent to the control rats, revealing that the OFC did not have decisive roles in extinction acquisition. Together with our previous study, we suggest that the OFC only interferes with fear regulation when it becomes pathophysiologically hyperactive.

Analysis of collateral projections from the lateral orbitofrontal cortex to nucleus accumbens and basolateral amygdala in rats.

The orbitofrontal cortex (OFC) is an important brain area for executive functions. The OFC projects to both the nucleus accumbens (NAc) and the basolateral nucleus of the amygdala (BLA). These two pathways share some similar behavioral functions, but their anatomical and physiological properties have not been compared before. In this study, we first explored the connection of the lateral OFC (lOFC) to NAc core (NAcc) and/or BLA, especially the collateral projections (experiments 1 and 2) with rats. In experiment 1, fluorophore-conjugated retrograde tracers were locally infused into the NAcc and the BLA to sample neurons in the lOFC. Our results revealed that along the anterior-posterior axis of the lOFC, more NAcc- and/or BLA-projecting neurons were distributed toward the posterior end, but the average percentage of collateral projecting neurons at the four sampled lOFC levels remained fairly stable. In experiment 2, antidromic single units in the lOFC responsive to the NAcc and/or the BLA stimulation were identified in anesthetized rats. However, we found that collateral projections from the lOFC to NAcc and BLA were sparse. We next studied the physiological characteristics of these two pathways (experiment 3). In this experiment, orthodromic single units in the NAcc or the BLA responsive to the lOFC stimulation were located in anesthetized rats. Our results showed no difference in the evoked thresholds or the intensity-response probability curves between the two. Together, our results showed that these two pathways were similar in projecting neuron distribution and physiological characteristics.NEW & NOTEWORTHY Using the double retrograde tracing and electrophysiological approach, we reported that among the sampled NAcc- or the BLA-projecting lOFC neurons, the percentage of collateral projections were fairly stable (about 20%-25%) along the lOFC anterior-posterior axis. Furthermore, among the neurons sampled in the NAcc and the BLA, there was no difference in physiological characteristics in response to lOFC stimulation between the two pathways.

Medial or lateral orbitofrontal cortex activation during fear extinction differentially regulates fear renewal.

Some anxiety-related disorders, such as panic disorder, specific phobia, post-traumatic stress disorder (PTSD), and obsessive-compulsive disorder (OCD), develop because of the poor regulation and inappropriate expression of fear-related behavior at the wrong place and wrong time. In clinical settings, exposure therapy, which consists of repeated presentation of trauma-related stimuli without real threats in the therapeutic context, is commonly used to treat these disorders. However, 30-50 % of patients suffer from the recurrence of anxiety symptoms after they leave the therapeutic context. This behavioral phenomenon is called renewal. In this study, ABA Pavlovian fear renewal paradigm was used to assess the role of the aberrant orbitofrontal cortex (OFC) activation, a symptom of OCD patients, on fear regulation in laboratory settings. The rats were fear conditioned in one context (context A), extinguished to the tones in another context (context B), and then tested in either context A or B. During extinction, rats were subjected to lateral or medial OFC activation. We found that rats that underwent extinction with either lateral or medial OFC activation were unable to use the context to determine whether it was a safe or dangerous context during renewal test. Interestingly, the rats with lateral OFC activation during extinction showed generally high fear, whereas the rats with medial OFC activation during extinction showed generally low fear. In conclusion, our results suggested that aberrant activation of specifically the lateral OFC may have a negative impact during exposure therapy treatments and results in their poor regulation of fear-related behavior.

Remarkably High Hole Mobility Metal-Oxide Thin-Film Transistors.

High performance p-type thin-film transistor (p-TFT) was realized by a simple process of reactive sputtering from a tin (Sn) target under oxygen ambient, where remarkably high field-effect mobility (µ FE ) of 7.6 cm2/Vs, 140 mV/dec subthreshold slope, and 3 × 104 on-current/off-current were measured. In sharp contrast, the SnO formed by direct sputtering from a SnO target showed much degraded µ FE , because of the limited low process temperature of SnO and sputtering damage. From the first principle quantum-mechanical calculation, the high hole µ FE of SnO p-TFT is due to its considerably unique merit of the small effective mass and single hole band without the heavy hole band. The high performance p-TFTs are the enabling technology for future ultra-low-power complementary-logic circuits on display and three-dimensional brain-mimicking integrated circuits.

Remarkably High Mobility Thin-Film Transistor on Flexible Substrate by Novel Passivation Material.

High mobility thin-film transistor (TFT) is crucial for future high resolution and fast response flexible display. Remarkably high performance TFT, made at room temperature on flexible substrate, is achieved with record high field-effect mobility (µ FE ) of 345 cm2/Vs, small sub-threshold slope (SS) of 103 mV/dec, high on-current/off-current (I ON /I OFF ) of 7 × 106, and a low drain-voltage (VD) of 2 V for low power operation. The achieved mobility is the best reported data among flexible electronic devices, which is reached by novel HfLaO passivation material on nano-crystalline zinc-oxide (ZnO) TFT to improve both I ON and I OFF . From X-ray photoelectron spectroscopy (XPS) analysis, the non-passivated device has high OH-bonding intensity in nano-crystalline ZnO, which damage the crystallinity, create charged scattering centers, and form potential barriers to degrade mobility.

New Material Transistor with Record-High Field-Effect Mobility among Wide-Band-Gap Semiconductors.

At an ultrathin 5 nm, we report a new high-mobility tin oxide (SnO2) metal-oxide-semiconductor field-effect transistor (MOSFET) exhibiting extremely high field-effect mobility values of 279 and 255 cm(2)/V-s at 145 and 205 °C, respectively. These values are the highest reported mobility values among all wide-band-gap semiconductors of GaN, SiC, and metal-oxide MOSFETs, and they also exceed those of silicon devices at the aforementioned elevated temperatures. For the first time among existing semiconductor transistors, a new device physical phenomenon of a higher mobility value was measured at 45-205 °C than at 25 °C, which is due to the lower optical phonon scattering by the large SnO2 phonon energy. Moreover, the high on-current/off-current of 4 × 10(6) and the positive threshold voltage of 0.14 V at 25 °C are significantly better than those of a graphene transistor. This wide-band-gap SnO2 MOSFET exhibits high mobility in a 25-205 °C temperature range, a wide operating voltage of 1.5-20 V, and the ability to form on an amorphous substrate, rendering it an ideal candidate for multifunctional low-power integrated circuit (IC), display, and brain-mimicking three-dimensional IC applications.