Introduction: Stepping and arm swing are stereotyped movements that require coordination across m... more Introduction: Stepping and arm swing are stereotyped movements that require coordination across multiple muscle groups. It is not known whether the encoding of these stereotyped movements in the human primary motor cortex is confined to the limbs' respective somatotopy. Methods: We recorded subdural electrocorticography activities from the hand/arm area in the primary motor cortex of 6 subjects undergoing deep brain stimulation surgery for essential tremor and Parkinson's disease who performed stepping (all patients) and arm swing (n = 3 patients) tasks. Results: We show stepping-related low frequency oscillations over the arm area. Furthermore, we show that this oscillatory activity is separable, both in frequency and spatial domains, from gamma band activity changes that occur during arm swing. Discussion: Our study contributes to the growing body of evidence that lower extremity movement may be more broadly represented in the motor cortex, and suggest that it may represent a way to coordinate stereotyped movements across the upper and lower extremities.
Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing bo... more 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. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activa...
The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to r... more 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. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feedingrelated behavior. Our study overlays information about the type, function and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.
When animals engage in reward-seeking behaviors such as foraging or hunting, they often expose th... more When animals engage in reward-seeking behaviors such as foraging or hunting, they often expose themselves to potential threats, and they must assess competing signals that may trigger conflicting motivational drives. The ability to appropriately weigh competing environmental cues and execute appropriate behavioral responses is paramount for survival and a key feature of mental health, yet little is known about the neural circuits that underpin this ability. For decades, the amygdala has been identified as a focal point in emotional processing and is thought to be a hub for translating sensory information into motivated behaviors 1,2. The BLA is important for the acquisition, encoding and retrieval of both positive and negative associations, and plasticity occurs in BLA neurons upon the encoding of cues that predict either positive or negative outcomes 3–8. The BLA also shows prominent neuronal correlates of reward-seeking and fear-related responses in seminaturalistic tasks in which animals need to forage and retrieve food in the presence of imminent predator-like threats 9,10. An important target of the BLA thought to be crucial for the coordination of reward-seeking and fear-related behaviors is the medial prefrontal cortex (mPFC) 11–13 , which receives robust monosynaptic glutamatergic inputs from the BLA 14,15 and sends a reciprocal connection in return 16. Like the BLA, the mPFC has been widely implicated in the regulation of both reward-seeking 17,18 and fear-related behavior 19–21 , and pharmacological inactivation of the mPFC produces deficits in the coordination of these behaviors 22,23. Furthermore, the mPFC shows prominent neuronal responses that are highly correlated with the time course of behavioral manifestations of reward-seeking and fear-related behavior 11,18. While some studies have examined the necessity of BLA activity for fear-related signaling in the mPFC 24,25 , little is known about how dynamic interactions between these structures may govern the coordination of reward-seeking and fear-related behavior upon presentation of competing signals. In this study, we focus on the PL subregion of the mPFC, though some experiments may also influence BLA projections to other subregions of mPFC. In this study, we used electrophysiological recordings, optoge-netically mediated photoidentification of BLA→PL neurons and supervised machine learning algorithms to decode behavior during competition, along with circuit-specific manipulations during a modified Pavlovian cue discrimination task in which conditioned stimuli predicting either sucrose or shock were presented separately on some trials and simultaneously in others. We address several questions. Is correlated firing between the BLA and PL dynamic upon presentations of cues associated with positive (rewards) or negative (punishments) outcomes? What is the directionality of information flow? Can we use neural activity and behavior during Pavlovian discrimination to accurately decode the behavior of an animal during the presentation of conflicting signals? And finally, is the BLA→PL projection necessary for and sufficient to promote fear-related behavior? We also examined whether either brain region was particularly sensitive to the sucrose-predictive or the shock-predictive cue. We found that predominantly excitatory cross-correlations (CCs) between the BLA and PL developed a BLA→PL directionality during the shock-predictive but not the sucrose-predictive cue. On the basis of this finding, we hypothesized that this projection supplies information 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 between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock-and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.
Introduction: Stepping and arm swing are stereotyped movements that require coordination across m... more Introduction: Stepping and arm swing are stereotyped movements that require coordination across multiple muscle groups. It is not known whether the encoding of these stereotyped movements in the human primary motor cortex is confined to the limbs' respective somatotopy. Methods: We recorded subdural electrocorticography activities from the hand/arm area in the primary motor cortex of 6 subjects undergoing deep brain stimulation surgery for essential tremor and Parkinson's disease who performed stepping (all patients) and arm swing (n = 3 patients) tasks. Results: We show stepping-related low frequency oscillations over the arm area. Furthermore, we show that this oscillatory activity is separable, both in frequency and spatial domains, from gamma band activity changes that occur during arm swing. Discussion: Our study contributes to the growing body of evidence that lower extremity movement may be more broadly represented in the motor cortex, and suggest that it may represent a way to coordinate stereotyped movements across the upper and lower extremities.
Projections from the lateral hypothalamus (LH) to the ventral tegmental area (VTA), containing bo... more 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. We provide evidence that photostimulation of the GABAergic LH-VTA component, but not the glutamatergic component, increases dopamine (DA) release in the nucleus accumbens (NAc) via inhibition of local VTA GABAergic neurons. Our study clarifies how GABAergic LH inputs to the VTA can contribute to generalized behavioral activa...
The lateral hypothalamic (LH) projection to the ventral tegmental area (VTA) has been linked to r... more 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. We reveal that the LH sends excitatory and inhibitory input onto VTA dopamine (DA) and GABA neurons, and that the GABAergic projection drives feedingrelated behavior. Our study overlays information about the type, function and connectivity of LH neurons and identifies a neural circuit that selectively controls compulsive sugar consumption, without preventing feeding necessary for survival, providing a potential target for therapeutic interventions for compulsive-overeating disorder.
When animals engage in reward-seeking behaviors such as foraging or hunting, they often expose th... more When animals engage in reward-seeking behaviors such as foraging or hunting, they often expose themselves to potential threats, and they must assess competing signals that may trigger conflicting motivational drives. The ability to appropriately weigh competing environmental cues and execute appropriate behavioral responses is paramount for survival and a key feature of mental health, yet little is known about the neural circuits that underpin this ability. For decades, the amygdala has been identified as a focal point in emotional processing and is thought to be a hub for translating sensory information into motivated behaviors 1,2. The BLA is important for the acquisition, encoding and retrieval of both positive and negative associations, and plasticity occurs in BLA neurons upon the encoding of cues that predict either positive or negative outcomes 3–8. The BLA also shows prominent neuronal correlates of reward-seeking and fear-related responses in seminaturalistic tasks in which animals need to forage and retrieve food in the presence of imminent predator-like threats 9,10. An important target of the BLA thought to be crucial for the coordination of reward-seeking and fear-related behaviors is the medial prefrontal cortex (mPFC) 11–13 , which receives robust monosynaptic glutamatergic inputs from the BLA 14,15 and sends a reciprocal connection in return 16. Like the BLA, the mPFC has been widely implicated in the regulation of both reward-seeking 17,18 and fear-related behavior 19–21 , and pharmacological inactivation of the mPFC produces deficits in the coordination of these behaviors 22,23. Furthermore, the mPFC shows prominent neuronal responses that are highly correlated with the time course of behavioral manifestations of reward-seeking and fear-related behavior 11,18. While some studies have examined the necessity of BLA activity for fear-related signaling in the mPFC 24,25 , little is known about how dynamic interactions between these structures may govern the coordination of reward-seeking and fear-related behavior upon presentation of competing signals. In this study, we focus on the PL subregion of the mPFC, though some experiments may also influence BLA projections to other subregions of mPFC. In this study, we used electrophysiological recordings, optoge-netically mediated photoidentification of BLA→PL neurons and supervised machine learning algorithms to decode behavior during competition, along with circuit-specific manipulations during a modified Pavlovian cue discrimination task in which conditioned stimuli predicting either sucrose or shock were presented separately on some trials and simultaneously in others. We address several questions. Is correlated firing between the BLA and PL dynamic upon presentations of cues associated with positive (rewards) or negative (punishments) outcomes? What is the directionality of information flow? Can we use neural activity and behavior during Pavlovian discrimination to accurately decode the behavior of an animal during the presentation of conflicting signals? And finally, is the BLA→PL projection necessary for and sufficient to promote fear-related behavior? We also examined whether either brain region was particularly sensitive to the sucrose-predictive or the shock-predictive cue. We found that predominantly excitatory cross-correlations (CCs) between the BLA and PL developed a BLA→PL directionality during the shock-predictive but not the sucrose-predictive cue. On the basis of this finding, we hypothesized that this projection supplies information 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 between these reciprocally connected structures to coordinate behavior is unknown. We recorded neuronal activity from the BLA and PL while rats performed a task wherein competing shock-and sucrose-predictive cues were simultaneously presented. The correlated firing primarily displayed a BLA→PL directionality during the shock-associated cue. Furthermore, BLA neurons optogenetically identified as projecting to PL more accurately predicted behavioral responses during competition than unidentified BLA neurons. Finally photostimulation of the BLA→PL projection increased freezing, whereas both chemogenetic and optogenetic inhibition reduced freezing. Therefore, the BLA→PL circuit is critical in governing the selection of behavioral responses in the face of competing signals.
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Papers by Kara Presbrey