David J. Anderson
The Neurobiology of Emotional Behavior
Research interests in my laboratory focus on understanding how emotional behavior is encoded in the brain, at the level of specific neuronal circuits, and the specific neuronal subtypes that comprise them. We want to understand the structure and dynamic properties of these circuits and how they give rise to the outward behavioral expressions of emotions such as fear, anxiety or anger. This information will provide a framework for understanding how and where in the brain emotions are influenced by genetic variation and environmental influence ("nature" and "nurture"), and may someday lead to improved drugs to treat psychiatric disorders such as depression. We are using both mice and the vinegar fly Drosophila melanogaster as model systems. A central focus of the laboratory is on the neural circuits underlying aggression and fear. We are using molecular genetic tools, as well as functional imaging and electrophysiology, to establish cause-and-effect relationships between the activity of specific neuronal circuits and behavior. We hope that this research will lead to new insights into the organization of emotion circuits, and their dysregulation in psychiatric disorders.
Emotion circuits in the mouse brain
Research using the laboratory mouse Mus musculus focuses on understanding the neurobiology of fear, anxiety and aggression, and the interrelationships between the circuitry that processes these emotions.
Neurobiology of Fear and Anxiety
Our studies of fear are currently centered on the function of circuits in the amygdala, a medial temporal lobe structure that plays an important role in Pavlovian learned fear, a form of classical conditioning. We have identified genes that mark several subpopulations of neurons that form a dynamic microcircuit within the central nucleus of the amygdala (Haubensak et al., 2010). The function of this microcircuit in fear behavior is being dissected using optogenetic tools, such as channelrhodopsin, and pharmacogenetic tools, such as the ivermectin-gated glutamate sensitive chloride channel (GluCl) (Lerchner et al. 2007), together with acute slice electrophysiology and genetically based anatomical tracing of synaptic pathways. More recent studies have applied optogenetic approaches to dissecting the neural circuitry of the lateral septum, a relatively under-studied structure that plays an important role in the control of stress-induced anxiety.
Neurobiology of Aggression
Aggression is a naturally occurring, instinctive social behavior, but pathological violence takes an enormous toll on human society. Yet the neurobiology of aggressive behavior is tremendously understudied by comparison to other emotional and affective behaviors, such as fear and anxiety. It has been known for almost a century that electrical stimulation of certain regions of the hypothalamus can elicit attack behavior. However the identity of the neurons responsible for this behavior, their precise location, connectivity with other brain regions, and their relationship to neurons mediating other social behaviors, such as mating, are unknown. Furthermore, most such studies have been performed in cats and rats, limiting the applicability of genetic tools. We have recently shown that optogenetic stimulation of neurons in the ventromedial hypothalamic nucleus (VMH), using a virally expressed channelrhodopsin-2 (ChR2), can evoke attack in male mice that is time-locked to the light stimulus, not only towards a female (which is normally never attacked), but also towards an inanimate object such as a latex glove. Interestingly, electrophysiological recordings in awake behaving mice indicate that VMH contains intermingled populations of neurons that are involved in either male-male aggression, or male-female mating. Our current studies have identified molecular markers for attack neurons, opening the way to mapping the circuitry through which these neurons influence aggressive behavior, and their relationship to neurons controlling mating. These studies should lead to a better understanding of how internal states, such as arousal or motivation, are translated into behavioral action-selection ("decision-making").
Neural circuits for "emotional" behavior in Drosophila
The pioneering work of the late Seymour Benzer proved that the powerful genetics of Drosophila can be used to dissect the genetic underpinnings of many types of complex behaviors. Until recently, however, it was not clear whether this model system could also be applied to understanding the neurobiology of emotion and affect. We are taking two complementary approaches to determine the extent to which this is possible, and if so what we can learn from it. One approach is to dissect the neural circuitry underlying behaviors that are analogous to defensive behaviors in higher organisms, such as aggression (Wang et al., 2008; Wang and Anderson, 2009). The other is to model internal states or processes that are fundamental to many types of emotional responses, such as arousal, to ask for example whether arousal is unitary, or whether there are different types of behavior-specific arousal states (Lebestky et al., 2009). In both cases, we are developing novel behavioral assays, as well as machine vision-based approaches (Dankert et al., 2009) to automate the measurement of these behaviors (in collaboration with Pietro Perona, Allen E. Puckett Professor of Electrical Engineering), and are using molecular genetic-based tools to image and perturb neuronal activity in order to identify the specific circuits that mediate these behaviors.
Adolphs, Ralph and Anderson, David (2013) Social and emotional neuroscience: Editorial overview. Current Opinion in Neurobiology, 23 (3). pp. 291-293. ISSN 0959-4388.http://resolver.caltech.edu/CaltechAUTHORS:20130919-125746689
Vrontou, Sophia et al. (2013) Genetic identification of C fibres that detect massage-like stroking of hairy skin in vivo. Nature, 493 (7434). pp. 669-673. ISSN 0028-0836.http://resolver.caltech.edu/CaltechAUTHORS:20130221-102159444
Tayler, Timothy D. et al. (2012) A neuropeptide circuit that coordinates sperm transfer and copulation duration in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 109 (50). pp. 20697-20702. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20130118-102141430
Anderson, David J. (2012) Optogenetics, Sex, and Violence in the Brain: Implications for Psychiatry. Biological Psychiatry, 71 (12). pp. 1081-1089. ISSN 0006-3223 . http://resolver.caltech.edu/CaltechAUTHORS:20120625-091939881
Burgos-Artizzu, Xavier P. et al. (2012) Social behavior recognition in continuous video. In: 2012 IEEE Conference on Computer Vision and Pattern Recognition (CVPR). IEEE , Piscataway, NJ, pp. 1322-1329. ISBN 978-1-4673-1226-4 http://resolver.caltech.edu/CaltechAUTHORS:20120731-115125060
Hergarden, Anne Christina and Tayler, Timothy D. and Anderson, David J. (2012) Allatostatin-A neurons inhibit feeding behavior in adult Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 109 (10). pp. 3967-3972. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20120327-134518305
Inagaki, Hidehiko K. et al. (2012) Visualizing Neuromodulation In Vivo: TANGO-Mapping of Dopamine Signaling Reveals Appetite Control of Sugar Sensing. Cell, 148 (3). pp. 583-595. ISSN 0092-8674.http://resolver.caltech.edu/CaltechAUTHORS:20120312-110130340
Lo, Liching and Anderson, David J. (2011) A Cre-Dependent, Anterograde Transsynaptic Viral Tracer for Mapping Output Pathways of Genetically Marked Neurons. Neuron, 72 (6). pp. 938-950. ISSN 0896-6273.http://resolver.caltech.edu/CaltechAUTHORS:20120203-094246153
Lukaszewicz, Agnès I. and Anderson, David J. (2011) Cyclin D1 promotes neurogenesis in the developing spinal cord in a cell cycle-independent manner. Proceedings of the National Academy of Sciences of the United States of America, 108 (28). pp. 11632-11637. ISSN 0027-8424.http://resolver.caltech.edu/CaltechAUTHORS:20110725-095339268
Wang, Liming et al. (2011) Hierarchical chemosensory regulation of male-male social interactions in Drosophila.Nature Neuroscience, 14 (6). pp. 757-762. ISSN 1097-6256.http://resolver.caltech.edu/CaltechAUTHORS:20110614-081823526
Lin, Dayu et al. (2011) Functional identification of an aggression locus in the mouse hypothalamus. Nature, 470 (7333). pp. 221-226. ISSN 0028-0836. http://resolver.caltech.edu/CaltechAUTHORS:20110303-095335546
Haubensak, Wulf et al. (2010) Genetic dissection of an amygdala microcircuit that gates conditioned fear.Nature, 468 (7321). pp. 270-276. ISSN 0028-0836. http://resolver.caltech.edu/CaltechAUTHORS:20101206-112525797
Shields, Shannon D. et al. (2010) Pain behavior in the formalin test persists after ablation of the great majority of C-fiber nociceptors. Pain, 151 (2). pp. 422-429. ISSN 0304-3959.http://resolver.caltech.edu/CaltechAUTHORS:20101104-074429356
Guan, Yun et al. (2010) Mas-related G-protein–coupled receptors inhibit pathological pain in mice. Proceedings of the National Academy of Sciences of the United States of America, 107 (36). pp. 15933-15938. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20100928-094220816
Wang, Liming and Anderson , David J. (2010) Identification of an aggression-promoting pheromone and its receptor neurons in Drosophila. Nature, 463 (7278). pp. 227-232. ISSN 0028-0836.http://resolver.caltech.edu/CaltechAUTHORS:20100128-135258031
Liu, Qin et al. (2009) Sensory Neuron-Specific GPCR Mrgprs Are Itch Receptors Mediating Chloroquine-Induced Pruritus. Cell, 139 (7). pp. 1353-1365. ISSN 0092-8674. http://resolver.caltech.edu/CaltechAUTHORS:20100119-100309565
Lebestky, Tim et al. (2009) Two Different Forms of Arousal in Drosophila Are Oppositely Regulated by the Dopamine D1 Receptor Ortholog DopR via Distinct Neural Circuits. Neuron, 64 (4). pp. 522-536. ISSN 0896-6273. http://resolver.caltech.edu/CaltechAUTHORS:20100106-144427131
Imamachi, Noritaka et al. (2009) TRPV1-expressing primary afferents generate behavioral responses to pruritogens via multiple mechanisms. Proceedings of the National Academy of Sciences of the United States of America, 106 (27). pp. 11330-11335. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:20090820-164722093
Rau, Kristofer K. et al. (2009) Mrgprd Enhances Excitability in Specific Populations of Cutaneous Murine Polymodal Nociceptors. Journal of Neuroscience, 29 (26). pp. 8612-8619. ISSN 0270-6474.http://resolver.caltech.edu/CaltechAUTHORS:20090908-094020207
Cavanaugh, Daniel J. et al. (2009) Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli. Proceedings of the National Academy of Sciences of the United States of America, 106 (22). pp. 9075-9080. ISSN 0027-8424.http://resolver.caltech.edu/CaltechAUTHORS:20090814-100042259
Dankert, Heiko et al. (2009) Automated monitoring and analysis of social behavior in Drosophila. Nature Methods, 6 (4). pp. 297-303. ISSN 1548-7091. http://resolver.caltech.edu/CaltechAUTHORS:20090601-135542919
Yorozu, Suzuko et al. (2009) Distinct sensory representations of wind and near-field sound in the Drosophila brain. Nature, 458 (7235). pp. 201-206. ISSN 0028-0836.http://resolver.caltech.edu/CaltechAUTHORS:20090708-133728189
Ng, Lydia et al. (2009) An anatomic gene expression atlas of the adult mouse brain. Nature Neuroscience, 12 (3). pp. 356-362. ISSN 1097-6256. http://resolver.caltech.edu/CaltechAUTHORS:20090922-113531843
Wang, Liming et al. (2008) A common genetic target for environmental and heritable influences on aggressiveness in Drosophila. Proceedings of the National Academy of Sciences of the United States of America, 105 (15). pp. 5657-5663. ISSN 0027-8424. http://resolver.caltech.edu/CaltechAUTHORS:WANpnas08