Correlational patterns of neuronal activation and epigenetic marks in the basolateral amygdala and piriform cortex following olfactory threat conditioning and extinction in rats.

Introduction: Cumulative evidence suggests that sensory cortices interact with the basolateral amygdala (BLA) defense circuitry to mediate threat conditioning, memory retrieval, and extinction learning. The olfactory piriform cortex (PC) has been posited as a critical site for olfactory associative memory. Recently, we have shown that N-methyl-D-aspartate receptor (NMDAR)-dependent plasticity in the PC critically underpins olfactory threat extinction. Aging-associated impairment of olfactory threat extinction is related to the hypofunction of NMDARs in the PC. Methods: In this study, we investigated activation of neuronal cFos and epigenetic marks in the BLA and PC using immunohistochemistry, following olfactory threat conditioning and extinction learning in rats. Results: We found highly correlated cFos activation between the posterior PC (pPC) and BLA. cFos was correlated with the degree of behavioral freezing in the pPC in both adult and aged rats, and in the BLA only in adult rats. Markers of DNA methylation 5 mC and histone acetylation H3K9/K14ac, H3K27ac, and H4ac exhibited distinct training-, region-, and age-dependent patterns of activation. Strong correlations of epigenetic marks between the BLA and pPC in adult rats were found to be a general feature. Conversely, aged rats only exhibited correlations of H3 acetylations between the two structures. Histone acetylation varied as a function of aging, revealed by a reduction of H3K9/K14ac and an increase of H4ac in aged brains at basal condition and following threat conditioning. Discussion: These findings underscore the coordinated role of PC and BLA in olfactory associative memory storage and extinction, with implications for understanding aging related cognitive decline.

Olfactory threat extinction in the piriform cortex: An age-dependent employment of NMDA receptor-dependent long-term depression.

Extinction of threat memory is a measure of behavioral flexibility. In the absence of additional reinforcement, the extinction of learned behaviors allows animals and humans to adapt to their changing environment. Extinction mechanisms and their therapeutic implications for maladaptive learning have been extensively studied. However, how aging affects extinction learning is much less understood. Using a rat model of olfactory threat extinction, we show that the extinction of olfactory threat memory is impaired in aged Sprague-Darley rats. Following extinction training, long-term depression (LTD) in the piriform cortex (PC) was inducible ex vivo in aged rats and was NMDA receptor (NMDAR)-independent. On the other hand, adult rats acquired successful olfactory threat extinction, and LTD was not inducible following extinction training. Neuronal cFos activation in the posterior PC correlated with learning and extinction performance in rats. NMDAR blockade either systemically or locally in the PC during extinction training prevented successful extinction in adult rats, following which NMDAR-dependent LTD became inducible ex vivo. This suggests that extinction learning employs NMDAR-dependent LTD mechanisms in the PC of adult rats, thus occluding further LTD induction ex vivo. The rescue of olfactory threat extinction in aged rats by D-cycloserine, a partial NMDAR agonist, suggests that the impairment in olfactory threat extinction of aged animals may relate to NMDAR hypofunctioning and a lack of NMDAR-dependent LTD. These findings are consistent with an age-related switch from NMDAR-dependent to NMDAR-independent LTD in the PC. Optimizing NMDAR function in sensory cortices may improve learning and flexible behavior in the aged population.

The motion of long bubbles in microchannels using a meter-long, rectangular capillary on a chip.

HYPOTHESIS: The dynamics of gas-liquid interfaces differs between aqueous surfactant and nanoparticle mixtures in rectangular cross-section capillaries. EXPERIMENTS: We designed and fabricated a new microfluidic device with a meter-long channel and a noncircular cross section (35 µm by 100 µm by 1 m) to study the flow behavior of long bubbles in capillaries wetted by water as well as surfactant and nanoparticle solutions. Flow in the novel symmetric loop device maintains essentially straight and inertialess conditions over a wide range of flow rates. FINDINGS: The pressure-drop versus velocity relationship of long bubbles in capillaries with noncircular cross sections has been studied theoretically but not extensively validated. The measured pressure drop (normalized with respect to interfacial properties) experienced by bubbles varies as Ca2/3 over the range 10-7

A micro-scale rheometer to study foam texture and flow resistance in planar fractures.

We designed and fabricated a new microfluidic device to better enable study of foam microstructure and rheology in planar fractures. The design phase included stress-strain finite element analysis to enhance the pressure tolerance of the device. The optimized design is a 2 cm wide by 7.75 cm long rough fracture that includes 25 posts to anchor the glass cover plate. The posts simulate asperities and provide structural support during bonding of a glass cover plate to the device. Importantly, the new design illustrates improved ability to sustain large differential pressure compared to previous designs in the literature. The rheometer permits study of the relationship among foam bubble morphology, pressure drop, and flow rates. Our findings validated the previous, sparse microvisual studies mentioned in the literature and confirmed that small quality foam, ranging from 20 to 50% gas by volume, contains dispersed bubbles separated by liquid lenses. In this range, the distribution of bubble sizes was roughly 80-90% small uniform bubbles and only 10-20% of larger and more elongated bubbles. Additionally, our studies reveal that foam apparent viscosity is a strong function of foam quality, velocity, and texture (i.e., bubble size). Apparent viscosity of foam ranged from 100 to 600 cP for the conditions studied. High quality foams in fractures are independent of gas flow rates but very sensitive to liquid flow rates. On the other hand, low quality foams are sensitive to gas flow rates but independent of liquid flow rates.