Kay M Tye

Kay M Tye
Massachusetts Institute of Technology | MIT · Department of Brain and Cognitive Sciences

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98
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Publications

Publications (98)
Article
Full-text available
The ability to associate temporally segregated information and assign positive or negative valence to environmental cues is paramount for survival. Studies have shown that different projections from the basolateral amygdala (BLA) are potentiated following reward or punishment learning1–7. However, we do not yet understand how valence-specific infor...
Preprint
Rationale The basolateral amygdala (BLA) and medial geniculate nucleus of the thalamus (MGN) have both been shown to be necessary for the formation of associative learning. While the role that the BLA plays in this process has long been emphasized, the MGN has been less well-studied and surrounded by debate regarding whether the relay of sensory in...
Article
Social signals can serve as potent emotional triggers with powerful impacts on processes from cognition to valence processing. How are social signals dynamically and flexibly associated with positive or negative valence? How do our past social experiences and present social standing shape our motivation to seek or avoid social contact? We discuss a...
Article
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Across species, animals organize into social dominance hierarchies that serve to decrease aggression and facilitate survival of the group. Neuroscientists have adopted several model organisms to study dominance hierarchies in the laboratory setting, including fish, reptiles, rodents and primates. We review recent literature across species that shed...
Preprint
Basal forebrain cholinergic neurons are thought to modulate how organisms process and respond to environmental stimuli through impacts on arousal, attention, memory, and motivated behavior. We questioned whether basal forebrain cholinergic neurons are directly involved in conditioned behavior, independent of ancillary roles in stimulus processing....
Article
Social homeostasis is the ability of individuals to detect the quantity and quality of social contact, compare it to an established set-point in a command center, and adjust the effort expended to seek the optimal social contact expressed via an effector system. Social contact becomes a positive or negative valence stimulus when it is deficient or...
Chapter
An essential component in animal behavior is the ability to process emotion and dissociate among positive and negative valence in response to a rewarding or aversive stimulus. The medial prefrontal cortex (mPFC)—responsible for higher order executive functions that include cognition, learning, and working memory; and is also involved in sociability...
Preprint
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The advancement of behavioral analysis in neuroscience has been aided by the development of computational tools 1,2 . Specifically, computer vision algorithms have emerged as a powerful tool to elevate behavioral research 3,4 . Yet fully automatic analysis of social behavior remains challenging in two ways. First, existing tools to track and analyz...
Article
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When people are forced to be isolated from each other, do they crave social interactions? To address this question, we used functional magnetic resonance imaging to measure neural responses evoked by food and social cues after participants (n = 40) experienced 10 h of mandated fasting or total social isolation. After isolation, people felt lonely a...
Article
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In a complex and dynamic environment, the brain flexibly adjusts its circuits to preferentially process behaviorally relevant information. Here, we investigated how the olfactory bulb copes with this demand by examining the plasticity of adult-born granule cells (abGCs). We found that learning of olfactory discrimination elevates odor responses of...
Article
Methods for one-photon fluorescent imaging of calcium dynamics can capture the activity of hundreds of neurons across large fields of view at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk from neuropil, resulting in a decreased signal-to-noise ratio and art...
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What individual differences in neural activity predict the future escalation of alcohol drinking from casual to compulsive? The neurobiological mechanisms that gate the transition from moderate to compulsive drinking remain poorly understood. We longitudinally tracked the development of compulsive drinking across a binge-drinking experience in male...
Preprint
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Methods for one-photon fluorescent imaging of calcium dynamics in vivo are popular due to their ability to simultaneously capture the dynamics of hundreds of neurons across large fields of view, at a low equipment complexity and cost. In contrast to two-photon methods, however, one-photon methods suffer from higher levels of crosstalk between cell...
Article
Long-range synchronization of neural oscillations correlates with distinct behaviors, yet its causal role remains unproven. In mice, tests of avoidance behavior evoke increases in theta-frequency (∼8 Hz) oscillatory synchrony between the ventral hippocampus (vHPC) and medial prefrontal cortex (mPFC). To test the causal role of this synchrony, we dy...
Article
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Substantial progress has been made in our understanding of the neural circuits involved in fear. This has been a cross-species endeavor, yet—as debated here—there are disparities on how to investigate and define fear. We hope that the debate presented here, which represents the views of a subset of outstanding researchers in the field, will invigor...
Article
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Social connections are vital to survival throughout the animal kingdom and are dynamic across the life span. There are debilitating consequences of social isolation and loneliness, and social support is increasingly a primary consideration in health care, disease prevention, and recovery. Considering social connection as an “innate need,” it is hyp...
Article
Decades of research suggest that the mesocortical dopamine system exerts powerful control over mPFC physiology and function. Indeed, dopamine signaling in the medial prefrontal cortex (mPFC) is implicated in a vast array of processes, including working memory, stimulus discrimination, stress responses, and emotional and behavioral control. Conseque...
Article
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Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3–6, where neural activi...
Preprint
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We propose a statistical framework for clustering multiple time series that exhibit nonlinear dynamics into an a-priori-unknown number of sub-groups that each comprise time series with similar dynamics. Our motivation comes from neuroscience where an important problem is to identify, within a large assembly of neurons, sub-groups that respond simil...
Article
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In this issue of Nature Neuroscience, Menegas et al. demonstrate a role for midbrain dopamine neurons projecting to the tail of the striatum in encoding stimulus novelty and threat avoidance. From this study emerges a model whereby distinct dopaminergic projections to striatum influence behavior along at least two axes, one representing value and o...
Preprint
The problem of detecting changes in firing patterns in neural data is studied. The problem is formulated as a quickest change detection problem. Important algorithms from the literature are reviewed. A new algorithmic technique is discussed to detect deviations from learned baseline behavior. The algorithms studied can be applied to both spike and...
Article
Observational learning is a powerful survival tool allowing individuals to learn about threat-predictive stimuli without directly experiencing the pairing of the predictive cue and punishment. This ability has been linked to the anterior cingulate cortex (ACC) and the basolateral amygdala (BLA). To investigate how information is encoded and transmi...
Article
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Recombinant rabies viral vectors have proven useful for applications including retrograde targeting of projection neurons and monosynaptic tracing, but their cytotoxicity has limited their use to short-term experiments. Here we introduce a new class of double-deletion-mutant rabies viral vectors that left transduced cells alive and healthy indefini...
Preprint
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In the quest for food, we may expend effort and increase our vulnerability to potential threats. Motivation to seek food is dynamic, varying with homeostatic need. What mechanisms underlie these changes? Basolateral amygdala neurons projecting to the nucleus accumbens (BLA-NAc) preferentially encode positive valence, whereas those targeting the cen...
Article
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The basolateral amygdala (BLA) mediates associative learning for both fear and reward. Accumulating evidence supports the notion that different BLA projections distinctly alter motivated behavior, including projections to the nucleus accumbens (NAc), medial aspect of the central amygdala (CeM), and ventral hippocampus (vHPC). Although there is cons...
Article
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Stress is a risk factor for many neuropsychiatric disorders, and the mesolimbic dopamine (DA) pathway is a crucial node of vulnerability. Despite the high prevalence of stress-related neuropsychiatric disorders in women, preclinical knowledge on the impact of stress on neural circuitry has predominantly been acquired in males. Here, we examine how...
Article
Activity remodels neurons, altering their molecular, structural, and electrical characteristics. To enable the selective characterization and manipulation of these neurons, we present FLARE, an engineered transcription factor that drives expression of fluorescent proteins, opsins, and other genetically encoded tools only in the subset of neurons th...
Article
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Orchestrating appropriate behavioral responses in the face of competing signals that predict either rewards or threats in the environment is crucial for survival. The basolateral nucleus of the amygdala (BLA) and prelimbic (PL) medial prefrontal cortex have been implicated in reward-seeking and fear-related responses, but how information flows betw...
Article
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 breakthroug...
Article
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 pop...
Article
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 comp...
Article
Full-text available
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....
Article
Full-text available
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...
Article
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On the anniversary of the Boyden et al. (2005) paper that introduced the use of channelrhodopsin in neurons, Nature Neuroscience asks selected members of the community to comment on the utility, impact and future of this important technique.
Article
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The basolateral amygdala (BLA) and the medial prefrontal cortex (mPFC) modulate anxiety and social behaviors. It remains to be elucidated, however, whether direct projections from the BLA to the mPFC play a functional role in these behaviors. We used optogenetic approaches in behaving mice to either activate or inhibit BLA inputs to the mPFC during...
Article
(Cell 160, 528–541; January 29, 2015) During the preparation of our paper, we mistakenly labeled the y axis in Figure 7I, describing the gnawing response of mice during photoactivation of the GABAergic component of the LH-VTA projections, as well as the y axes in Figures S4J, S4L, S4M, and S7E–S7H, depicting the results of the behavioral tests in t...
Article
Full-text available
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...
Article
Full-text available
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...
Article
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. I...
Article
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...
Article
Full-text available
Disruptions in circadian rhythms and dopaminergic activity are involved in the pathophysiology of bipolar disorder, though their interaction remains unclear. Moreover, a lack of animal models that display spontaneous cycling between mood states has hindered our mechanistic understanding of mood switching. Here, we find that mice with a mutation in...
Article
Theoretically, harnessing the brain's own endogenous plasticity mechanisms could serve to alter both internal states and external behavior in a therapeutic manner.
Article
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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...
Article
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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 r...
Article
Full-text available
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...
Article
Mutations in phosphatase and tensin homolog deleted on chromosome ten (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...
Article
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...
Article
Full-text available
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...
Article
Full-text available
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 socia...
Article
Full-text available
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 o...
Data
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