Electroolfactogram (EOG) Recording in the Mouse Main Olfactory Epithelium

Olfactory sensory neurons in the main olfactory epithelium (MOE) are responsible for detecting odorants and EOG recording is a reliable approach to analyze the peripheral olfactory function. However, recently we revealed that rodent MOE can also detect the air pressure caused by airflow. The sensation of airflow pressure and odorants may function in synergy to facilitate odorant perception during sniffing. We have reported that the pressure-sensitive response in the MOE can also be assayed by EOG recording. Here we describe procedures for pressure-sensitive as well as odorant-stimulated EOG measurement in the mouse MOE. The major difference between the pressure-sensitive EOG response and the odorant-stimulated response was whether to use pure air puff or use an odorized air puff

Stimulation of electro-olfactogram responses in the main olfactory epithelia by airflow depends on the type 3 adenylyl cyclase

Cilia of olfactory sensory neurons are the primary sensory organelles for olfaction. The detection of odorants by the main olfactory epithelium (MOE) depends on coupling of odorant receptors to the type 3 adenylyl cyclase (AC3) in olfactory cilia. We monitored the effect of airflow on electro-olfactogram (EOG) responses and found that the MOE of mice can sense mechanical forces generated by airflow. The airflow-sensitive EOG response in the MOE was attenuated when cAMP was increased by odorants or by forskolin suggesting a common mechanism for airflow and odorant detection. In addition, the sensitivity to airflow was significantly impaired in the MOE from AC3−/− mice. We conclude that AC3 in the MOE is required for detecting the mechanical force of airflow, which in turn may regulate odorant perception during sniffing

Type 1 adenylyl cyclase is essential for maintenance of remote contextual fear memory

Although molecular mechanisms for hippocampus-dependent memory have been extensively studied, much less is known about signaling events important for remote memory. Here we report that mice lacking type 1 adenylyl cyclase (AC1) are able to establish and retrieve remote contextual memory but unable to sustain it as long as wild-type mice. Interestingly, mice overexpressing AC1 show superior remote contextual memory even though they exhibit normal hippocampus-dependent contextual memory. These data illustrate that calcium coupling to cAMP contributes to the stability of remote memory and identifies AC1 as a potential drug target site to improve long-term remote memory

Disruption of type 3 adenylyl cyclase expression in the hypothalamus leads to obesity

Evidence from human studies and transgenic mice lacking the type 3 adenylyl cyclase (AC3) indicates that AC3 plays a role in the regulation of body weight. It is unknown in which brain region AC3 exerts such an effect. We examined the role of AC3 in the hypothalamus for body weight control using a floxed AC3 mouse strain. Here, we report that AC3 flox/flox mice became obese after the administration of AAV-CRE-GFP into the hypothalamus. Both male and female AC3 floxed mice showed heavier body weight than AAV-GFP injected control mice. Furthermore, mice with selective ablation of AC3 expression in the ventromedial hypothalamus also showed increased body weight and food consumption. Our results indicated that AC3 in the hypothalamus regulates energy balance

Modulation of Neuronal Signal Transduction and Memory Formation by Synaptic Zinc

The physiological role of synaptic zinc has remained largely enigmatic since its initial detection in hippocampal mossy fibers over 50 years ago. The past few years have witnessed a number of studies highlighting the ability of zinc ions to regulate ion channels and intracellular signaling pathways implicated in neuroplasticity, and others that shed some light on the elusive role of synaptic zinc in learning and memory. Recent behavioral studies using knock-out mice for the synapse-specific zinc transporter ZnT-3 indicate that vesicular zinc is required for the formation of memories dependent on the hippocampus and the amygdala, two brain centers that are prominently innervated by zinc-rich fibers. A common theme emerging from this research is the activity-dependent regulation of the Erk1/2 mitogen-activated-protein kinase pathway by synaptic zinc through diverse mechanisms in neurons. Here we discuss current knowledge on how synaptic zinc may play a role in cognition through its impact on neuronal signaling

Overexpression of the type 1 adenylyl cyclase in the forebrain leads to deficits of behavioral inhibition

The type 1 adenylyl cyclase (AC1) is an activity-dependent, calcium-stimulated adenylyl cyclase expressed in the nervous system that is implicated in memory formation. We examined the locomotor activity, and impulsive and social behaviors of AC1+ mice, a transgenic mouse strain overexpressing AC1 in the forebrain. Here we report that AC1+ mice exhibit hyperactive behaviors and demonstrate increased impulsivity and reduced sociability. In contrast, AC1 and AC8 double knock-out mice are hypoactive, and exhibit increased sociability and reduced impulsivity. Interestingly, the hyperactivity of AC1+ mice can be corrected by valproate, a mood-stabilizing drug. These data indicate that increased expression of AC1 in the forebrain leads to deficits in behavioral inhibition

Genetic disruption of the core circadian clock impairs hippocampus-dependent memory

Perturbing the circadian system by electrolytically lesioning the suprachiasmatic nucleus (SCN) or varying the environmental light:dark schedule impairs memory, suggesting that memory depends on the circadian system. We used a genetic approach to evaluate the role of the molecular clock in memory. Bmal1−/− mice, which are arrhythmic under constant conditions, were examined for hippocampus-dependent memory, LTP at the Schaffer-collateral synapse, and signal transduction activity in the hippocampus. Bmal1−/− mice exhibit impaired contextual fear and spatial memory. Furthermore, LTP in hippocampal slices from Bmal1−/− mice is also significantly decreased relative to that from wild-type mice. Activation of Erk1,2 MAP kinase (MAPK) during training for contextual fear memory and diurnal oscillation of MAPK activity and cAMP in the hippocampus is also lost in Bmal1−/− mice, suggesting that the memory defects are due to reduction of the memory consolidation pathway in the hippocampus. We conclude that critical signaling events in the hippocampus required for memory depend on BMAL1

Flow and transport experiments for a streambank seep originating from a preferential flow pathway

Streambank seeps commonly originate from localized heterogeneity or preferential flow pathways (PFPs) in riparian floodplains. However, limited field data have been reported on ground water seep flows and solute transport to seeps from PFPs. The objective of this research was to build upon previous floodplain-scale investigations of PFPs by analyzing seep discharge and transport characteristics through a single PFP. An important research question was whether this PFP could be conceptualized as a homogeneous, one-dimensional flow path. Streambank seep discharge measurements were obtained by inducing a hydraulic head in a trench injection system. Also, co-injection of Rhodamine WT (RhWT) and a potassium chloride (KCl) tracer over a 60-min period was used to investigate transport dynamics. Seep discharge and breakthrough curves for electrical conductivity (EC) and RhWT were measured at the streambank using a lateral flow collection device. The breakthrough curves were fit to one-dimensional convective-dispersion equations (CDEs) to inversely estimate solute transport parameters. The PFP from which the seep originated was clean, coarse gravel (6% by mass less than 2.0 mm) surrounded by gravel with finer particles (20% by mass less than 2.0 mm). Located approximately 2 m from the trench, the seep (50 cm by 10 cm area) required at least 40 cm of hydraulic head for flow to emerge at the streambank. At a higher hydraulic head of 125 cm, seep discharge peaked at 3.5 L/min. This research verified that localized PFPs can result in the rapid transport of water (hydraulic conductivity on the order of 400 m/d) and solutes once reaching a sufficient near-bank hydraulic head. A one-dimensional equilibrium CDE was capable of simulating the EC (R2 = 0.94) and RhWT (R2 = 0.91) breakthrough curves with minimal RhWT sorption (distribution coefficient, Kd, equal to 0.1 cm3/g). Therefore, the PFP could be conceptualized as a one-dimensional, homogenous flow and transport pathway. These results are consistent with previous research observing larger-scale phosphorus transport

Effect of Parameter Distributions on Uncertainty Analysis of Hydrologic Models

Increasing concern about the accuracy of hydrologic and water quality models has prompted interest in procedures for evaluating the uncertainty associated with these models. If a Monte Carlo simulation is used in an uncertainty analysis, assumptions must be made relative to the probability distributions to assign to the model input parameters. Some have indicated that since these parameters can not be readily determined, uncertainty analysis is of limited value. In this article we have evaluated the impact of parameter distribution assumptions on estimates of model output uncertainty. We conclude that good estimates of the means and variances of the input parameters are of greater importance than the actual form of the distribution. This conclusion is based on an analysis using the AGNPS model