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Kay Tye

Gillian A Matthews, Kay M Tye
Stepping out of an aggressively air-conditioned building into the sweltering heat evokes a number of thermoregulatory responses, both autonomic (sweating) and behavioral (peeling off a layer of clothing or seeking an iced beverage). Just as we come out of the hottest part of the summer, a study by Tan and colleagues provides an exciting breakthrough in our ability to study the neural mechanisms of keeping cool when it's hot.
September 22, 2016: Cell
Edward H Nieh, Caitlin M Vander Weele, Gillian A Matthews, Kara N Presbrey, Romy Wichmann, Christopher A Leppla, Ehsan M Izadmehr, Kay M Tye
Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing both GABAergic and glutamatergic components, encode conditioned responses and control compulsive reward-seeking behavior. GABAergic neurons in the LH have been shown to mediate appetitive and feeding-related behaviors. Here we show that the GABAergic component of the LH-VTA pathway supports positive reinforcement and place preference, while the glutamatergic component mediates place avoidance. In addition, our results indicate that photoactivation of these projections modulates other behaviors, such as social interaction and perseverant investigation of a novel object...
June 15, 2016: Neuron
Anna Beyeler, Praneeth Namburi, Gordon F Glober, Clémence Simonnet, Gwendolyn G Calhoon, Garrett F Conyers, Robert Luck, Craig P Wildes, Kay M Tye
Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA...
April 20, 2016: Neuron
Gillian A Matthews, Edward H Nieh, Caitlin M Vander Weele, Sarah A Halbert, Roma V Pradhan, Ariella S Yosafat, Gordon F Glober, Ehsan M Izadmehr, Rain E Thomas, Gabrielle D Lacy, Craig P Wildes, Mark A Ungless, Kay M Tye
The motivation to seek social contact may arise from either positive or negative emotional states, as social interaction can be rewarding and social isolation can be aversive. While ventral tegmental area (VTA) dopamine (DA) neurons may mediate social reward, a cellular substrate for the negative affective state of loneliness has remained elusive. Here, we identify a functional role for DA neurons in the dorsal raphe nucleus (DRN), in which we observe synaptic changes following acute social isolation. DRN DA neurons show increased activity upon social contact following isolation, revealed by in vivo calcium imaging...
February 11, 2016: Cell
Praneeth Namburi, Ream Al-Hasani, Gwendolyn G Calhoon, Michael R Bruchas, Kay M Tye
In order to thrive, animals must be able to recognize aversive and appetitive stimuli within the environment and subsequently initiate appropriate behavioral responses. This assignment of positive or negative valence to a stimulus is a key feature of emotional processing, the neural substrates of which have been a topic of study for several decades. Until recently, the result of this work has been the identification of specific brain regions, such as the basolateral amygdala (BLA) and nucleus accumbens (NAc), as important to valence encoding...
June 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Gwendolyn G Calhoon, Kay M Tye
Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts...
October 2015: Nature Neuroscience
Antoine Adamantidis, Silvia Arber, Jaideep S Bains, Ernst Bamberg, Antonello Bonci, György Buzsáki, Jessica A Cardin, Rui M Costa, Yang Dan, Yukiko Goda, Ann M Graybiel, Michael Häusser, Peter Hegemann, John R Huguenard, Thomas R Insel, Patricia H Janak, Daniel Johnston, Sheena A Josselyn, Christof Koch, Anatol C Kreitzer, Christian Lüscher, Robert C Malenka, Gero Miesenböck, Georg Nagel, Botond Roska, Mark J Schnitzer, Krishna V Shenoy, Ivan Soltesz, Scott M Sternson, Richard W Tsien, Roger Y Tsien, Gina G Turrigiano, Kay M Tye, Rachel I Wilson
No abstract text is available yet for this article.
September 2015: Nature Neuroscience
Praneeth Namburi, Anna Beyeler, Suzuko Yorozu, Gwendolyn G Calhoon, Sarah A Halbert, Romy Wichmann, Stephanie S Holden, Kim L Mertens, Melodi Anahtar, Ada C Felix-Ortiz, Ian R Wickersham, Jesse M Gray, Kay M Tye
The ability to differentiate stimuli predicting positive or negative outcomes is critical for survival, and perturbations of emotional processing underlie many psychiatric disease states. Synaptic plasticity in the basolateral amygdala complex (BLA) mediates the acquisition of associative memories, both positive and negative. Different populations of BLA neurons may encode fearful or rewarding associations, but the identifying features of these populations and the synaptic mechanisms of differentiating positive and negative emotional valence have remained unknown...
April 30, 2015: Nature
Michelle M Sidor, Thomas J Davidson, Kay M Tye, Melissa R Warden, Karl Diesseroth, Colleen A McClung
The ability to probe defined neural circuits in awake, freely-moving animals with cell-type specificity, spatial precision, and high temporal resolution has been a long sought tool for neuroscientists in the systems-level search for the neural circuitry governing complex behavioral states. Optogenetics is a cutting-edge tool that is revolutionizing the field of neuroscience and represents one of the first systematic approaches to enable causal testing regarding the relation between neural signaling events and behavior...
January 15, 2015: Journal of Visualized Experiments: JoVE
Edward H Nieh, Gillian A Matthews, Stephen A Allsop, Kara N Presbrey, Christopher A Leppla, Romy Wichmann, Rachael Neve, Craig P Wildes, Kay M Tye
The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to reward processing, but the computations within the LH-VTA loop that give rise to specific aspects of behavior have been difficult to isolate. We show that LH-VTA neurons encode the learned action of seeking a reward, independent of reward availability. In contrast, LH neurons downstream of VTA encode reward-predictive cues and unexpected reward omission. We show that inhibiting the LH-VTA pathway reduces "compulsive" sucrose seeking but not food consumption in hungry mice...
January 29, 2015: Cell
Patricia H Janak, Kay M Tye
The amygdala has long been associated with emotion and motivation, playing an essential part in processing both fearful and rewarding environmental stimuli. How can a single structure be crucial for such different functions? With recent technological advances that allow for causal investigations of specific neural circuit elements, we can now begin to map the complex anatomical connections of the amygdala onto behavioural function. Understanding how the amygdala contributes to a wide array of behaviours requires the study of distinct amygdala circuits...
January 15, 2015: Nature
Kay M Tye
Theoretically, harnessing the brain's own endogenous plasticity mechanisms could serve to alter both internal states and external behavior in a therapeutic manner.
September 17, 2014: Neuron
Stephen A Allsop, Caitlin M Vander Weele, Romy Wichmann, Kay M Tye
Many psychiatric illnesses are characterized by deficits in the social domain. For example, there is a high rate of co-morbidity between autism spectrum disorders and anxiety disorders. However, the common neural circuit mechanisms by which social deficits and other psychiatric disease states, such as anxiety, are co-expressed remains unclear. Here, we review optogenetic investigations of neural circuits in animal models of anxiety-related behaviors and social behaviors and discuss the important role of the amygdala in mediating aspects of these behaviors...
2014: Frontiers in Behavioral Neuroscience
Amy S Chuong, Mitra L Miri, Volker Busskamp, Gillian A C Matthews, Leah C Acker, Andreas T Sørensen, Andrew Young, Nathan C Klapoetke, Mike A Henninger, Suhasa B Kodandaramaiah, Masaaki Ogawa, Shreshtha B Ramanlal, Rachel C Bandler, Brian D Allen, Craig R Forest, Brian Y Chow, Xue Han, Yingxi Lin, Kay M Tye, Botond Roska, Jessica A Cardin, Edward S Boyden
Optogenetic inhibition of the electrical activity of neurons enables the causal assessment of their contributions to brain functions. Red light penetrates deeper into tissue than other visible wavelengths. We present a red-shifted cruxhalorhodopsin, Jaws, derived from Haloarcula (Halobacterium) salinarum (strain Shark) and engineered to result in red light-induced photocurrents three times those of earlier silencers. Jaws exhibits robust inhibition of sensory-evoked neural activity in the cortex and results in strong light responses when used in retinas of retinitis pigmentosa model mice...
August 2014: Nature Neuroscience
Lisa A Gunaydin, Logan Grosenick, Joel C Finkelstein, Isaac V Kauvar, Lief E Fenno, Avishek Adhikari, Stephan Lammel, Julie J Mirzabekov, Raag D Airan, Kelly A Zalocusky, Kay M Tye, Polina Anikeeva, Robert C Malenka, Karl Deisseroth
Social interaction is a complex behavior essential for many species and is impaired in major neuropsychiatric disorders. Pharmacological studies have implicated certain neurotransmitter systems in social behavior, but circuit-level understanding of endogenous neural activity during social interaction is lacking. We therefore developed and applied a new methodology, termed fiber photometry, to optically record natural neural activity in genetically and connectivity-defined projections to elucidate the real-time role of specified pathways in mammalian behavior...
June 19, 2014: Cell
Anna Beyeler, Christine A Eckhardt, Kay M Tye
Optogenetics has accelerated the field of neuroscience by overcoming many of the spatial, genetic, and temporal limitations of previous techniques to control neural activity. The study of learning and memory has profoundly benefited from these tools mainly from their use in rodents. New insights have been made regarding the involvement of specific cell types or populations of synapses in the acquisition, consolidation, and retrieval of memories. The cellular specificity and temporal precision of optogenetic manipulations have also shown to be useful to study synaptic mechanisms supporting learning and memory including long-term synaptic plasticity...
2014: Progress in Molecular Biology and Translational Science
Ada C Felix-Ortiz, Kay M Tye
Impairments in social interaction represent a core symptom of a number of psychiatric disease states, including autism, schizophrenia, depression, and anxiety. Although the amygdala has long been linked to social interaction, little is known about the functional role of connections between the amygdala and downstream regions in noncompetitive social behavior. In the present study, we used optogenetic and pharmacological tools in mice to study the role of projections from the basolateral complex of the amygdala (BLA) to the ventral hippocampus (vHPC) in two social interaction tests: the resident-juvenile-intruder home-cage test and the three chamber sociability test...
January 8, 2014: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Michael E Haws, Thomas C Jaramillo, Felipe Espinosa, Allie J Widman, Garret D Stuber, Dennis R Sparta, Kay M Tye, Scott J Russo, Luis F Parada, Mihaela Stavarache, Michael Kaplitt, Antonello Bonci, Craig M Powell
Mutations in phosphatase and tensin homolog deleted on chromosome 10 (PTEN) are implicated in neuropsychiatric disorders including autism. Previous studies report that PTEN knockdown in neurons in vivo leads to increased spine density and synaptic activity. To better characterize synaptic changes in neurons lacking PTEN, we examined the effects of shRNA knockdown of PTEN in basolateral amygdala neurons on synaptic spine density and morphology by using fluorescent dye confocal imaging. Contrary to previous studies in the dentate gyrus, we find that knockdown of PTEN in basolateral amygdala leads to a significant decrease in total spine density in distal dendrites...
April 1, 2014: Journal of Comparative Neurology
Ada C Felix-Ortiz, Anna Beyeler, Changwoo Seo, Christopher A Leppla, Craig P Wildes, Kay M Tye
The basolateral amygdala (BLA) and ventral hippocampus (vHPC) have both been implicated in mediating anxiety-related behaviors, but the functional contribution of BLA inputs to the vHPC has never been directly investigated. Here we show that activation of BLA-vHPC synapses acutely and robustly increased anxiety-related behaviors, while inhibition of BLA-vHPC synapses decreased anxiety-related behaviors. We combined optogenetic approaches with in vivo pharmacological manipulations and ex vivo whole-cell patch-clamp recordings to dissect the local circuit mechanisms, demonstrating that activation of BLA terminals in the vHPC provided monosynaptic, glutamatergic inputs to vHPC pyramidal neurons...
August 21, 2013: Neuron
Sung-Yon Kim, Avishek Adhikari, Soo Yeun Lee, James H Marshel, Christina K Kim, Caitlin S Mallory, Maisie Lo, Sally Pak, Joanna Mattis, Byung Kook Lim, Robert C Malenka, Melissa R Warden, Rachael Neve, Kay M Tye, Karl Deisseroth
Behavioural states in mammals, such as the anxious state, are characterized by several features that are coordinately regulated by diverse nervous system outputs, ranging from behavioural choice patterns to changes in physiology (in anxiety, exemplified respectively by risk-avoidance and respiratory rate alterations). Here we investigate if and how defined neural projections arising from a single coordinating brain region in mice could mediate diverse features of anxiety. Integrating behavioural assays, in vivo and in vitro electrophysiology, respiratory physiology and optogenetics, we identify a surprising new role for the bed nucleus of the stria terminalis (BNST) in the coordinated modulation of diverse anxiety features...
April 11, 2013: Nature
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