The olfactory system of haematophagous insects, such as mosquitoes, plays a critical role in mediating innate responses to host odors. The ability to learn and remember information about their hosts can also modulate these responses, influencing processes such as host selection. Because of this, a better understanding of the mechanisms by which mosquitoes learn could open new research avenues for the development of control tools geared towards helping reduce disease transmission. To explore aversive olfactory conditioning in Aedes aegypti mosquitoes, we utilized a classical Pavlovian conditioning paradigm, training individuals by pairing a host-emitted odorant (conditioned stimulus, CS) with a mechanical shock mimicking host defensive behavior (unconditioned stimulus, US). Mosquitoes were then tested in a Y-maze olfactometer where they had to choose between an arm delivering the CS odor and a control arm. Videos of individual flight pathways within the olfactometer were tracked and instantaneous flight velocities were derived to further elucidate the nuances of naïve and trained mosquito flight patterns. Results showed that the success of olfactory conditioning was dependent upon the odorant used as a CS. Among the tested odors, mosquitoes only learned the association between 1-octen-3-ol and the US, switching their innate indifference into a learned aversion. Using a tethered flight LED arena that presents moving visual stimuli either independently or in conjunction with pulses of odor, the finer mechanisms of flight that lead to the observed change in decision-making were also investigated. Together, these results show that learning is a critical component of responses to host odors in Ae. aegypti. This work also investigates the finer mechanisms that underlie mosquitoes’ behavioral responses to learned odors, providing a more complete picture of aversive olfactory conditioning in mosquitoes and the overarching behavioral changes it incurs.

Observational studies in human infants have found associations between excessive exposure to non-normative stimulation, via television, and decreased cognitive ability and attention. A recent study has developed a rodent model to mimic this whereby mice are exposed to audio- visual stimuli (clips from cartoon network, flashing lights) for six hours a day starting at P10 until P52. When tested subsequently, excessively stimulated mice demonstrate increased risk taking, decreased anxiety, poorer short-term memory, and impaired learning relative to controls. In this study, we investigated the relationship between excessive non-normative stimulation (ENS) early in life and vulnerability to drugs of abuse in adulthood by studying conditioned place preference (CPP) to cocaine. The CPP paradigm is a standard behavioral model used to study the rewarding effects of drugs of abuse. The test apparatus consisted of a three-chambered box with two large chambers differing in wall pattern and floor design separated by a central neutral area. On day one (pre-conditioning) and day five (post-conditioning) the mice were free to explore all three chambers for 15 minutes while their time spent in each chamber was tracked. On days two-four mice were conditioned by pairing saline injections in the morning in one chamber and cocaine injections in the afternoon in the opposite chamber. Each mouse received a CPP score, calculated by the difference in time spent in the cocaine-paired chamber between day one and five. According to our results, both the control and ENS mice showed an increase in time spent in the cocaine-paired chamber on day five as compared to day one, but the excessively stimulated mice showed a larger CPP score. These results indicate that ENS in early development may lead to increased sensitivity to the rewarding properties of cocaine.

During the recovery period following morphine dependence, known as the protracted abstinence phase, there is a sensitive period where drug re-exposure increases drug-seeking behavior. In humans, this could manifest as a vulnerability to relapses. Even though this behavioral phase has been described in previous studies, the molecular mechanisms for how this is regulated are relatively unknown. Understanding the molecular mechanisms behind relapse could help in the development of therapeutic interventions for opiate addiction. Previous research in our lab has demonstrated that the kappa opioid receptor system (KOR) plays a key role in stress-induced relapse behaviors in rodent models of addiction. In this study, we will repeatedly inject mice with morphine to make them drug-dependent, and then reintroduce them to morphine while they are in the protracted abstinence phase. By comparing the differences in morphine-seeking behavior between wild-type and KOR transgenic mice, or following pharmacological blockade of KOR, we will further describe the mechanisms that are responsible for enhanced vulnerability to relapse during drug abstinence.

A brain-computer interface (BCI) consists of the hardware and software necessary to pick up and process signals from the brain in order to perform a task. The ultimate goal of this project is to develop a method to determine correlated firing of a group of neurons during a BCI task. The paradigm consists of a microelectrode array implanted in motor cortex, with neural activity transformed to control the movement of a cursor on a computer screen. Our goal is to use this approach to select the fewest necessary neuronal inputs for a given BCI, and to look at how this changes with learning. The first step in this task is model selection. We are using a modified autoregressive model to predict the firing of any given neuron based on the firing of all the other neurons in the ensemble and the position of the cursor. The model is a generalized linear model using a Poisson link function. We use a statistical analysis of this model in order to determine its efficacy and predictive power. We then employ a Granger Causality analysis to determine potential causal relations within the data set; determining potential connections and relations between neurons. We hope this will allow us to determine which neurons are necessary for a BCI task, how they behave, and how this changes with training and learning.

The brain is organized into intrinsic networks that support cognition and emotion. Functional magnetic resonance imaging (fMRI) has proven to be a useful tool in probing large-scale neural systems in living subjects. Using fMRI scans taken while subjects are at rest in a scanner, we can examine how these intrinsic systems are altered in developmentally abnormal individuals, who might struggle with a task. Researchers have suggested that autism spectrum disorders (ASD) are characterized by hyperconnectivity in intrinsic networks, but little is known about how network connectivity changes with development. In this study, we examined connectivity measures in ASD and typically developing (TD) groups (n = 496, ages 7-35) using fMRI scans retrieved from the Autism Brain Imaging Data Exchange repository. After screening for data quality, ASD and TD subjects were matched for age, motion, and intelligence. We calculated connectivity within five major intrinsic networks related to internally-directed thought, attention, and emotional processing (related to self and other). After preprocessing, we analyzed correlations between regions of interest within these networks to calculate individual within-network connectivity measures. We used linear regression to determine whether connectivity was predicted by age, diagnostic group, and their interaction. We found that age was related to decline in all connectivity measures in all five examined networks, possibly reflecting de-differentiation of network function. There was a selective difference by diagnostic group only in the “other” network. Subjects with ASD showed a steeper decline in connectivity with age (p = 0.045). Our results indicate that the “other” network may be a possible physiological marker of social symptom severity in autism, which we are now exploring. If so, it may be useful assessing effectiveness of intervention or therapy in autism.