Focusing on the right sensory input and translating that kernel of information into the proper behaviors is critical for finding food and mates and avoiding predation in one’s environment. I have a long-standing interest in understanding how the brain samples and processes information from the world around it to learn and control behavior. I have shown persistence in and dedication to studying difficult questions on circuit function and dendrite neurophysiology throughout my research career. My drive to generate impactful research findings has taught me how to adapt quickly to advancements in neuroscience research technologies.
Across systems, principal neurons effectively integrate thousands of noisy inputs in a strikingly similar fashion. My curiosity in the computational power of principal neurons and their role in information processing and sensory integration drives my passion and started my research career as a graduate student. For my Ph.D. thesis, I investigated the effects of glutamatergic, cholinergic, and dopaminergic modulation of the dendritic excitability of layer five cortical pyramidal neurons, in the laboratory of Dr. Srdjan D. Antic at the University of Connecticut Health Center (2009-2013). I investigated backpropagating action potentials, which bring calcium to postsynaptic sites to activate retrograde messengers, alter dendritic excitability, and ultimately shape mechanisms of synaptic plasticity, gain control, and the computational power of neural circuits. Using a combination of whole-cell patch-clamp and intracellular calcium and voltage imaging, I found that action potential backpropagation is highly variable and non-monotonically shaped by firing rate (Short et al., 2017), and modulated by exogenous iontophoretic dopamine (Wen-Liang et al., 2015; Wen-Liang et al., 2012) and glutamate applications (Oikonomou & Short et al. 2012). My thesis work highlights the importance of subtle changes in dendrite membrane excitability by local neurotransmitters in modulating spike-timing-dependent synaptic plasticity in principal neurons. This work inspired me to explore neural circuit function in vivo. I wanted to understand how these precise changes in the excitable properties of dendritic compartments translate to broader circuit function, and ultimately the animal’s sensory experiences and behavior. My training as a graduate student set the stage that allowed me to secure consistent independent funding across multiple grants for my entire postdoctoral training.
For my postdoctoral training (Drs. Justus Verhagen, Gordon Shepherd, and Matt Wachowiak), I transitioned to research olfactory bulb circuits in vivo, while continuing to use this model system to investigate the computational power of principal neurons: mitral and tufted cells. By studying a different neural system, I translated much of my knowledge of cortical circuits to the olfactory bulb, allowing me to have a unique and broader understanding of subcellular and neural circuit computations. I also advanced my imaging and electrophysiology experimental repertoire into in vivo preparations.
While working collaboratively between the Shepherd and Verhagen laboratories at Yale University, I created an experimental platform that integrated in vivo electrophysiology (to record mitral and tufted cells) with a digital micromirror device mediated optogenetic stimulation of olfactory sensory neurons expressing channelrhodopsin. For this project, I obtained independent T32 training grant funding through the Dept. of Neuroscience. I also picked up the necessary programming skills (Matlab, python, Tucker Davis Technologies, Neuron) to integrate the data acquisition, analysis platform, and perform additional modeling experiments. This work allowed me to generate some of the first spatiotemporal maps of input-output functions in the olfactory bulb. I found that excitatory responses in mitral and tufted cells were restricted to a particular respiratory phase. Our in silico modeling found that both increases in respiration rate and the strength of lateral inhibitory connectivity could tune phase-locking of mitral and tufted cell excitatory responses to particular periods of the respiratory cycle (Short et al. 2016). This work highlights the importance of respiration in mediating the temporal dynamics of odor information coding in the olfactory bulb.
While in the Verhagen Laboratory, I also had the privilege of being introduced to in vivo calcium imaging using a wide-field CCD camera (Rebello et al. 2014). This inspired my move to the Wachowiak Lab at the University of Utah, were I further advanced my imaging abilities by learning the latest in vivo two-photon imaging techniques. My postdoctoral work in Utah continued to make significant inroads into the question of how respiration shapes the transformation of sensory input to mitral and tufted cell circuits outputs. This work was funded by my NIDCD NRSA F32. I used genetically encoded calcium indicators to image inhalation-evoked dynamics of multiple cell subtypes in the OB: olfactory sensory neuron, short axon and periglomerular interneurons, and superficial and deep layer mitral and tufted cells (Short, Wachowiak, 2019). We found olfactory sensory neurons contributed to most of the temporal diversity seen in mitral and tufted cell population dynamics. Using dual-color two-photon imaging, we found that the diversity of superficial tufted cell temporal dynamics could originate within a glomerulus' microcircuit. This work highlights the importance of feedforward glomerular layer inhibition in shaping the temporal diversity of superficial tufted cells.
The research I conducted during my NSRA has resulted in generating a multitude of research projects which will become the foundation of my future laboratory. I am currently using genetically encoded glutamate sensors and two-color simultaneous imaging of principal neurons and interneurons to test proposed mechanisms of concentration-dependent processing in the olfactory bulb of awake and behaving mice. These projects have resulted in significant praise both as the Association for Chemoreception Sciences Polak Young Investigator's Awardee in 2019 and, more recently, a well-received presentation at the International Symposium on Olfaction and Taste. This work will result in two exciting stories, both of which will strongly impact how neuroscience understands stimulus intensity processing in the brain. I am also investigating dopamine's role in experience-dependent plasticity in the olfactory bulb, which is the focus of my research plan and is funded by my R21 NIDCD Early Career Research Award. With mastery of numerous techniques to dissect circuit computations across both cortical and olfactory bulb systems, I am well positioned to tackle the most challenging neuroscience questions pertaining to how the brain processes information. Not only do I already have a broad base of experimental techniques to draw from in my laboratory, but even more importantly, I have learned what it takes to establish the proper collaborations to test and implement the latest relevant technologies. I want to push the limits of our ability to research, dissect, image, and ultimately grasp how the brain works.