Melis Yilmaz Balban joined Dr. Andrew Huberman's lab in May 2016 as a postdoctoral fellow to study the neural circuits underlying visually guided defensive behaviors in rodent and primate models. In her PhD she studied roles of retinal circuits in the innate visual behaviors of mice in Markus Meister's lab at Harvard University. During the course of those studies, she discovered and characterized a powerful visual behavior: mice exhibit fast avoidance responses such as escape or freezing to expanding dark stimuli from above. Using cell-type-specific-ablations she tested the roles of different retinal cell types in these and others visual behaviors. Discovering innate behaviors and linking them to specific circuits are her main interests.
Honors & Awards
Peirce Fellowship, Harvard University (2009-2010)
Herchel Smith Graduate Fellowship, Herchel Smith Fund (2009-2011)
Doctor of Philosophy, Harvard University (2015)
Bachelor of Science, Stanford University, BIOL-BSH (2008)
Andrew Huberman, Postdoctoral Faculty Sponsor
Current Research and Scholarly Interests
I’m interested in understanding the neurobiology of fear and other innate responses. Fear is essential for our survival as people who have disorders that do not “feel” fear have a higher chance of death from accidents. On the other extreme, excessive or inappropriately expressed fear is a symptom of many psychiatric conditions such as PTSD, or other anxiety disorders. Even more common are the subtle forms of fear that many people feel in everyday life such as fear of failure or social interactions. These fears, though not immediately life-threatening, significantly limit our life quality and our ability to reach our full potential. Thus, understanding the neurobiology of fear at a mechanistic level: the cells and circuits involved and how they communicate with each other from perception to behavior- should be of major consequence for basic and translational neuroscience and psychology.
The definition of fear or any emotion for that matter is still an ongoing debate among psychologists and neuroscientists. How can one study an emotion that is hard to even define in scientific terms? Fear manifests itself most decisively through observable defensive behaviors. These behaviors provide the most objective handle for understanding of the underlying biological processes that drive fear. My work on mouse behaviors during my PhD inspired me to follow up and expand on this topic. For the fellowship period and the rest of my career, I would like to focus on the scientific issues described below.
Scientific areas of interest
Interspecies comparisons of defensive behavior
Almost all current human studies on fear responses and psychiatric illnesses are anthropocentric, treating behaviors as if they are unique to humans, even though various forms of defense exist is almost all organisms. This approach hinders us from identifying the basic components of the fear responses. Having a comparative multi-species understanding of the core mechanism of fear can help simplify this by putting human behaviors in perspective with other animal’s responses. Within mammals the mouse’s fear responses are the most heavily studied, however its evolutionary distance to humans makes it difficult for direct comparisons in terms of brain circuitry and behavior. Therefore primate models are an invaluable source for enabling both the study of neural circuits and sophistical behaviors that resemble those in humans, especially visual and social behaviors. This is why I would like to dedicate my time during the fellowship to establish visual defensive behavioral assays in the marmoset monkey and in order to bring intense mechanistic rigor to these studies develop genetic strategies to manipulate specific neurons involved in the perception and generation of fear responses. This will set the stage for my long-term future goals of finding common behavioral and neural circuit themes that extend across species.
Long term goals and potential implications of this work
My long-term objective is to develop such models of innate fear and test the predictions on healthy and unhealthy human populations to gain understanding into disease states. In the long run, I would like to build behavioral tests for humans using virtual reality platforms for immersive experiences and obtain objective behavioral measures of their responses. One can imagine doing this to identify the sub-components of the behaviors disrupted in each individual; this in turn should help formulize targeted behavioral and neural therapies. The vision is to pinpoint ways for the optogenetic and pharmacogenetic techniques developed in animals to be applied to humans in order to develop therapies highly tailored for the specific needs of individuals and their symptomology. As much as this might seem like science fiction now, species that bridge essential work in flies and mice to humans- namely, non-human primates, are an essential next step.
Andrew Huberman, Huberman (5/1/2016)
Human Responses to Visually Evoked Threat.
Current biology : CB
Vision is the primary sense humans use to evaluate and respond to threats. Understanding the biological underpinnings of the human threat response has been hindered by lack of realistic in-lab threat paradigms. We established an immersive virtual reality (VR) platform to simultaneously measure behavior, physiological state, and neural activity from the human brain using chronically implanted electrodes. Subjects with high anxiety showed increased visual scanning in response to threats as compared to healthy controls. In both healthy and anxious subjects, the amount of scanning behavior correlated with the magnitude of physiological arousal, suggesting that visual scanning behavior is directly linked to internal state. Intracranial electroencephalography (iEEG) recordings from three subjects suggested that high-frequency gamma activity in the insula positively correlates with physiological arousal induced by visual threats and that low-frequency theta activity in the orbitofrontal cortex (OFC) negatively correlates with physiological arousal induced by visual threats. These findings reveal a key role of eye movements and suggest that distinct insula and OFC activation dynamics may be important for detecting and adjusting human stress in response to visually perceived threats.
View details for DOI 10.1016/j.cub.2020.11.035
View details for PubMedID 33242389
Ventromedial hypothalamic neurons control a defensive emotion state
Defensive behaviors reflect underlying emotion states, such as fear. The hypothalamus plays a role in such behaviors, but prevailing textbook views depict it as an effector of upstream emotion centers, such as the amygdala, rather than as an emotion center itself. We used optogenetic manipulations to probe the function of a specific hypothalamic cell type that mediates innate defensive responses. These neurons are sufficient to drive multiple defensive actions, and required for defensive behaviors in diverse contexts. The behavioral consequences of activating these neurons, moreover, exhibit properties characteristic of emotion states in general, including scalability, (negative) valence, generalization and persistence. Importantly, these neurons can also condition learned defensive behavior, further refuting long-standing claims that the hypothalamus is unable to support emotional learning and therefore is not an emotion center. These data indicate that the hypothalamus plays an integral role to instantiate emotion states, and is not simply a passive effector of upstream emotion centers.
View details for DOI 10.7554/eLife.06633
View details for Web of Science ID 000351864100001
View details for PubMedID 25748136
Rapid Innate Defensive Responses of Mice to Looming Visual Stimuli
2013; 23 (20): 2011-2015
Much of brain science is concerned with understanding the neural circuits that underlie specific behaviors. While the mouse has become a favorite experimental subject, the behaviors of this species are still poorly explored. For example, the mouse retina, like that of other mammals, contains ∼20 different circuits that compute distinct features of the visual scene [1, 2]. By comparison, only a handful of innate visual behaviors are known in this species--the pupil reflex , phototaxis , the optomotor response , and the cliff response --two of which are simple reflexes that require little visual processing. We explored the behavior of mice under a visual display that simulates an approaching object, which causes defensive reactions in some other species [7, 8]. We show that mice respond to this stimulus either by initiating escape within a second or by freezing for an extended period. The probability of these defensive behaviors is strongly dependent on the parameters of the visual stimulus. Directed experiments identify candidate retinal circuits underlying the behavior and lead the way into detailed study of these neural pathways. This response is a new addition to the repertoire of innate defensive behaviors in the mouse that allows the detection and avoidance of aerial predators.
View details for DOI 10.1016/j.cub.2013.08.015
View details for Web of Science ID 000326317300022
View details for PubMedID 24120636