Johns Hopkins School of Medicine

Whether you’re a Baltimore native or coming to Johns Hopkins for the first time, you’ll find the Hopkins Neuroscience department is a place we come to call home. Our faculty and staff are committed to discovery, innovation and cutting edge insights. And we want to support you every step of the way.

Check out what some of our students and faculty have to say about their experience in our labs.

My time at Hopkins has been peppered with both triumphs and setbacks, but I haven’t once questioned my decision to join this department. Baltimore, as it turns out, is a wonderfully livable city, and an alleged reputation for competitiveness within the department never materialized. 

In truth, one of the most important things I’ve learned is how much success depends on the individual, as well as on picking the right advisor – and what makes an advisor ‘right’ varies greatly for each trainee. Luckily, there are excellent advisors here, ranging widely in experience, scientific interest, and mentoring style.

My mentor’s optimism and open-mindedness perfectly complement my independent streak. When I initially proposed projects that would use existing tools in the lab, Dr. Anto Bonci sent me back to the drawing table with a single instruction: Forget about the existing lab framework and come up with something you’re really excited to work on. So I did. I am now characterizing astrocytes in the midbrain and how they shape neurotransmission. This project is, in many ways, exactly what thesis projects shouldn’t be: It’s open-ended, it’s outside the expertise of my lab, and it had a long set-up process. It took me a while just to acquire the right tools and learn how to work with them. But despite months of trials and errors, I remain incredibly excited by the prospect of what I might find.

The project is ongoing, but I can now say with some confidence that astrocytes in the midbrain are molecularly and functionally distinct from their more popular counterparts in the cortex and spinal cord. In addition, I was surprised to find what appear to be subpopulations of oligodendrocytes, with potentially divergent roles. How this shapes cell-to-cell interactions and neuronal function is a fundamental question for neuroscience, and something I am actively trying to work out. But if neurons are like grapes and glia are the soil upon which they grow, you can imagine that, just as Merlot grapes are shaped by their surrounding terroir, regional differences in glial properties can have profound consequences on the survival and output of their neighboring neurons.

The arc of my graduate experience thus far has neither been perfect, nor unusual. But it has provided me with exactly what every grad student needs: a chance to take risks, to get comfortable with failure, to figure out what I’m really passionate about, and to mature as a scientist. For that, I am immensely grateful to my program, and the amazing mentor and colleagues it has given me.  And even on the most frustrating of science days, I can take a deep breath and push forward - because I know I wouldn’t be happy doing anything else.

I arrived in Baltimore and started at Hopkins as a graduate student five years ago. When I look back at my first year with the Neuroscience program, I'm amazed at how fast I've called it home. The fourteen classmates became my first family, as we bonded through sharing war stories of our course work, exams, and rotations. Faculty at Hopkins were also open and honest, easygoing while being exemplary at their job as scientists and mentors. I was pleasantly surprised at how close-knit and informal the Neuroscience family was, as we clearly experienced through our annual Neuroscience retreat. 

My classmates and I also learned to navigate the eclectic Baltimore scene, bar hopping throughout the city at night, going on nature walks and berry picking on weekends, and enjoying the endless street festivals that seem to occur almost weekly. 

It is easy to imagine now why I've felt at home so quickly. With the support of the programs, my friends old and new, and Baltimore as a backdrop, I am deeply invested in my home at Hopkins and Baltimore. 

I study neuronal regeneration in the Linden lab. Specifically, we are investigating the innate regenerative properties of serotonin neurons with fixed tissue and in vivo imaging as well as cell-specific genetic profiling. We hope this will offer insights into the mechanism by which serotonin neurons recover after injury.  The insights could potentially be applied to other neuronal cell types which otherwise do not recover following injury. 

When I first came to Johns Hopkins for my postdoctoral fellowship to study neuronal regeneration in the Linden lab, I was immediately struck by the community's overwhelming openness to collaboration and resource sharing as we worked on the chemical and neurobiological aspects of brain function. Our lab is investigating the innate regenerative properties of serotonin neurons to glean insights into how serotonin neurons recover after injury. By extension, we hope our findings are applicable to other neuronal cell types which otherwise do not recover following injury. 

I have been fortunate to be trained by senior scientists in a variety of techniques. I have access to top-of-the-line equipment within departmental core facilities and other laboratories to further my research using the best possible tools. And I have shared and received multiple mouse lines. The enthusiasm with which faculty and researchers share tools, supplies, and knowledge is not only motivating, but truly refreshing. 

In the darkness of the imaging facility, Wendy Zhang and I huddled around the computer, anxious to see the effects of a drug we had just acquired. On the monitor, flashes of fluorescence signaled that the cultured cochlea was healthy; groups of cells simultaneously became active and then silent, a pattern prevalent in many developing neural circuits. As the drug perfused into the imaging chamber, the activity from the genetically encoded calcium sensor slowed, and then ceased. I turned to Wendy, but she had already scampered out of the imaging facility, running down the hall to grab our PI, Dr. Dwight Bergles. Given the specificity of the drug, we had just identified a key receptor involved in initiating this activity in the inner ear.

In the Bergles’ Lab, we are interested in how spontaneous activity in the inner ear influences the development of the cochlea and auditory circuits. The activity we study happens before hearing begins; that is, the inner ear is generating activity that looks a lot like sound-driven activity. This is at a time when auditory circuits are drastically changing their architecture from broadly-tuned to sharply-tuned tonotopy that is prevalent in mature animals, leading us to hypothesize that this activity may provide the signal to refine connections in a Hebbian “fire together, wire together” way.

The molecular mechanisms of spontaneous activity generation have slowly been unraveled, leading us to develop new tools and techniques to assess the role of spontaneous activity in the development of the auditory system. We know that this activity is initiated by the release of ATP (although we don’t know how it is released). This ATP activates a Gq-coupled purinergic receptor on a group of cells known as Kölliker’s Organ, which ultimately leads to depolarization of inner hair cells and excitation of spiral ganglion neurons, the cells connecting the ear to the brain. By removing key components of the signaling cascade through genetic manipulations, we will begin to assess how spontaneous activity affects the development of the auditory system with a combination of immunohistochemistry, electrophysiology, in vitro and in vivo calcium imaging.

The availability and resourcefulness of my colleagues at Hopkins has made the work I am doing possible. This discovery happened during my rotation in the Bergles’ lab and has prompted my thesis work. While the experiments were performed with my hands, the mice were generated in part by Amit Agarwal, the calcium imaging technique and dissections were taught to me by Wendy Zhang, and Dr. Dwight Bergles provided, and continues to provide, great insights into the molecules and proteins involved in this pathway. The Hopkins culture encourages people to get together and share ideas and resources. This creates a truly synergistic environment that leads to cutting-edge research. Hopkins is truly an exciting place to be.

Our discovery that glial cells play a key role in inducing activity in the auditory system before hearing onset (published as an article in Nature in 2007) began with one serendipitous observation – that supporting cells in the developing cochlea exhibit ‘spontaneous’ inward currents. At the time, we were examining the mechanisms of glutamate clearance at ribbon synapses in cochleae isolated from young rodents in collaboration with Elisabeth Glowatzki (Department of Otolaryngology Head and Neck Surgery, JHU).  Supporting cells in these cochleae exhibited large inward currents in the absence of any stimulation, unlike glial cells in the brain. I remember thinking after the first day of recording that this could be a reflection of the spontaneous activity known to be produced within the cochlea. Two features of this activity – that it was extraordinarily robust, present in every supporting cell and in every cochlea that was examined, and that it was unusual for glial cells to exhibit this form of activity – convinced me that this phenomenon was worth investigating.  

We made the transformative discovery, also through serendipity, that supporting cells changed their shape when activated by ATP; thus, by simply imaging the cochlea from above, it was possible to observe when and where ATP was released. The change in shape was induced by loss of water, and these “crenation” events occurred most frequently in supporting cells located immediately adjacent to inner hair cells. It therefore seemed reasonable that if ATP activated groups of supporting cells, it could also activate nearby inner hair cells. In hair cells these periodic depolarizations triggered bursts of calcium spikes that led to bursts of action potentials in postsynaptic ganglion neurons. Moreover, in vivo recording from auditory centers of the brain prior to hearing onset revealed that the stereotyped firing behavior exhibited by spiral ganglion neurons is maintained as activity propagates through the auditory pathway. Remarkably, this activity ceases at hearing onset due to regression of the supporting cells, ensuring that spontaneous activity does not interfere with sound evoked activity. 

In several key observations since these initial experiments, recent selective genetic manipulations of supporting cells reaffirm the initial hypothesis that glial cells within the cochlea play an essential role in triggering spontaneous activity in auditory circuits of the brain. These findings have important implications for the most prevalent forms of inherited deafness, and tinnitus, a phenomenon in which sounds are perceived in the absence of an external stimulus. Understanding how activity promotes refinement of connections in auditory circuits and stimulates neuronal maturation could also help us devise new strategies for improving the performance of cochlear implants.