Activity of D1/2 Receptor Expressing Neurons in the Nucleus Accumbens Regulates Running, Locomotion, and Food Intake

While weight gain is clearly promoted by excessive energy intake and reduced expenditure, the underlying neural mechanisms of energy balance remain unclear. The NAc is one brain region that has received attention for its role in the regulation of energy balance; its D1 and D2 receptor containing neurons have distinct functions in regulating reward behavior and require further examination. The goal of the present study is to investigate how activation and inhibition of D1 and D2 neurons in the NAc influences behaviors related to energy intake and expenditure. Specific manipulation of D1 vs D2 neurons was done in both low expenditure and high expenditure (wheel running) conditions to assess behavioral effects in these different states. Direct control of neural activity was achieved using a DREADD (Designer Receptors Exclusively Activated by Designer Drugs) strategy. Activation of NAc D1 neurons increased food intake, wheel running and locomotor activity. In contrast, activation of D2 neurons in the NAc reduced running and locomotion while D2 neuron inhibition had opposite effects. These results highlight the importance of considering both intake and expenditure in the analysis of D1 and D2 neuronal manipulations. Moreover, the behavioral outcomes from D1 NAc neuronal manipulations depend upon the activity state of the animals (wheel running vs non-running). The data support and complement the hypothesis of specific NAc dopamine pathways facilitating energy expenditure and suggest a potential strategy for human weight control

Preference encoding in ventral pallidum mediates reward-seeking behavior

An essential function of the nervous system is to direct reward-seeking behavior in order to maximize the acquisition of preferred rewards. This process requires a method for evaluating all available outcomes on a common scale and using these valuations to organize the appropriate behavioral response. The ventral pallidum (VP) is a key node in a basal ganglia circuit hypothesized to convert limbic information, like reward values, into reward-seeking actions. Previous work has linked VP neural activity to the availability and palatability of rewards, and VP has been functionally implicated in the motivation to pursue rewards. Open questions include how VP encodes the values of multiple available rewards and whether its activity contributes to preference-driven behaviors. For this dissertation, we conducted a series of electrophysiological and optogenetic experiments to characterize the role of VP in navigating scenarios with multiple rewarding outcomes. First, we demonstrated that, following reward delivery, the activity of a majority VP neurons reflected the value of the delivered outcome relative to the locally available options; notably, this activity preceded and outnumbered reward-specific activity in nucleus accumbens, the most frequently studied input to VP. Further analysis of VP activity revealed that, consistent with a reward prediction error signal, a subset of neurons' reward-evoked activity incorporated the outcomes from the most recent previous trials. The prediction error hypothesis was further supported by optogenetic manipulations of VP activity during this epoch, which altered rats' engagement in the reward-seeking task according to changes in their estimate of the task's value. In a final set of experiments, we linked VP neural activity to the evolution of rats' choice behavior under changing physiological conditions and demonstrated a causal role for VP outcome signals in driving behavioral preference. Our results not only establish VP as a crucial site for encoding reward preferences; they also provide insight into fundamental principles of reward signaling in the nervous system, with particular consideration for the interface between prediction errors and preference, both static and dynamic

Preference encoding in ventral pallidum mediates reward-seeking behavior

An essential function of the nervous system is to direct reward-seeking behavior in order to maximize the acquisition of preferred rewards. This process requires a method for evaluating all available outcomes on a common scale and using these valuations to organize the appropriate behavioral response. The ventral pallidum (VP) is a key node in a basal ganglia circuit hypothesized to convert limbic information, like reward values, into reward-seeking actions. Previous work has linked VP neural activity to the availability and palatability of rewards, and VP has been functionally implicated in the motivation to pursue rewards. Open questions include how VP encodes the values of multiple available rewards and whether its activity contributes to preference-driven behaviors. For this dissertation, we conducted a series of electrophysiological and optogenetic experiments to characterize the role of VP in navigating scenarios with multiple rewarding outcomes. First, we demonstrated that, following reward delivery, the activity of a majority VP neurons reflected the value of the delivered outcome relative to the locally available options; notably, this activity preceded and outnumbered reward-specific activity in nucleus accumbens, the most frequently studied input to VP. Further analysis of VP activity revealed that, consistent with a reward prediction error signal, a subset of neurons' reward-evoked activity incorporated the outcomes from the most recent previous trials. The prediction error hypothesis was further supported by optogenetic manipulations of VP activity during this epoch, which altered rats' engagement in the reward-seeking task according to changes in their estimate of the task's value. In a final set of experiments, we linked VP neural activity to the evolution of rats' choice behavior under changing physiological conditions and demonstrated a causal role for VP outcome signals in driving behavioral preference. Our results not only establish VP as a crucial site for encoding reward preferences; they also provide insight into fundamental principles of reward signaling in the nervous system, with particular consideration for the interface between prediction errors and preference, both static and dynamic

zhounapeuw/NAPE_imaging_analysis: Initial

UW NAPE Imaging Preprocessing and Analysi

Reward activity in ventral pallidum tracks satiety-sensitive preference and drives choice behavior

A key function of the nervous system is producing adaptive behavior across changing conditions, like physiological state. Although states like thirst and hunger are known to impact decision-making, the neurobiology of this phenomenon has been studied minimally. Here, we tracked evolving preference for sucrose and water as rats proceeded from a thirsty to sated state. As rats shifted from water choices to sucrose choices across the session, the activity of a majority of neurons in the ventral pallidum, a region crucial for reward-related behaviors, closely matched the evolving behavioral preference. The timing of this signal followed the pattern of a reward prediction error, occurring at the cue or the reward depending on when reward identity was revealed. Additionally, optogenetic stimulation of ventral pallidum neurons at the time of reward was able to reverse behavioral preference. Our results suggest that ventral pallidum neurons guide reward-related decisions across changing physiological states

Encoding and context-dependent control of reward consumption within the central nucleus of the amygdala.

Dysregulation of the central amygdala is thought to underlie aberrant choice in alcohol use disorder, but the role of central amygdala neural activity during reward choice and consumption is unclear. We recorded central amygdala neurons in male rats as they consumed alcohol or sucrose. We observed activity changes at the time of reward approach, as well as lick-entrained activity during ongoing consumption of both rewards. In choice scenarios where rats could drink sucrose, alcohol, or quinine-adulterated alcohol with or without central amygdala optogenetic stimulation, rats drank more of stimulation-paired options when the two bottles contained identical options. Given a choice among different options, central amygdala stimulation usually enhanced consumption of stimulation-paired rewards. However, optogenetic stimulation during consumption of the less-preferred option, alcohol, was unable to enhance alcohol intake while sucrose was available. These findings indicate that the central amygdala contributes to refining motivated pursuit toward the preferred available option