Jamie Roitman, Ph.D. - US grants

DESCRIPTION (provided by applicant): The proposal is aimed at understanding the neural basis of numerical processing. To accomplish this, animal subjects will be trained to categorize a visual cue on the basis of the number of times it flashes. They will report whether the number of flashes is greater or less than five by making an eye movement to one of two possible visual targets that correspond to the choices. Other stimulus dimensions of the number cue will be controlled to insure that decisions are based on number. Parietal cortex has been implicated in both numerical processing and decision-making. It is hypothesized that temporary inactivation of posterior parietal cortex (PPC) will interfere with the ability to form decisions on the basis of number, but not color, information. Neurons in PPC respond to visual stimuli in a selective region of space and before eye movements to that location, the response field (RF). The responses of neurons in PPC suggest that they integrate information in order to guide eye movements. The activity of single PPC neurons will be recorded to determine if they represent the number cue itself and decisions about number. To gain insight into how number is represented in neural structures, the number cue will be placed in the neuron's RF and the profile of activity associated with number will be quantified. In addition, the choice target will be placed in the neuron's RF to measure neural activity associated with the integration of discrete pulses of information that guide the animal's choice.

[unreadable] DESCRIPTION (provided by applicant): The willingness to engage in risky behaviors is hallmark of drug addiction, gambling, and obesity. Presumably, one chooses to administer an illicit drug, over-consume a fat-laden meal, or put $1000 on red because the immediate outcome of the choice is potentially rewarding. The goal of this proposal is to identify patterns of activity in neural structures involved in evaluating rewards and making decisions between certain and risky outcomes that will inform how risk-preference is represented in the activity of single neurons. Rats will be trained to perform a Risk task, in which they choose between two levers in a test chamber that lead to different reward outcomes (sucrose pellets). Pressing the Certain lever always earns a Small reward, and pressing the Uncertain lever will either pay a Large reward or Omit the reward. Large or Omitted reward outcome is chosen randomly, so that subjects cannot track the number of Large outcomes to maximize overall payoffs across trials. In a forced response block, each lever will be presented alone on alternate trials, which provides the opportunity for the rat to equally sample both behavioral options and their associated consequences. This is followed by a free choice block, in which both levers are presented simultaneously and rats are able to select one. Analyses of choices will focus on risk-preference across sessions and the influence of reward-history on upcoming choices. While rats perform the Risk task we will record the electrophysiological activity of single neurons in the Nucleus Accumbens (NAc), which is critical for reward processing and in the Orbitofrontal cortex (OFC), an area thought to be important for making decisions based on reward outcome. In both NAc and OFC, we will measure responses to events leading up to, during, and following reward delivery or omission. The level of neural activity will be compared across the two behavioral responses (Certain-Uncertain), when freely chosen or not, and to the three possible outcomes (Small, Large, Omit). The long-term goal of our studies is to determine how aberrant signaling in these areas may underlie inaccurate representations of reward which may in turn lead to over-valuation of risky behaviors. PUBLIC HEALTH RELEVANCE: The pervasive problems associated with drug addiction, gambling, or overconsumption (of food or goods) stem from a willingness to engage in behaviors that yield risky outcomes. The goal of this project is to identify patterns of activity in neural structures involved in evaluating rewards and making decisions about choices with risky consequences that will inform how risk-preference is represented in the activity of single neurons. These studies have the potential to identify mechanisms of risk-prone behaviors and therefore new targets for their treatment. [unreadable] [unreadable] [unreadable]

DESCRIPTION (provided by applicant): Animals possess the flexibility to choose from a variety of behavioral responses in virtually every situation they encounter. Decision-making requires one to gather information from the senses to determine an appropriate behavioral response, taking into account the possible costs or rewards resulting from the alternatives. Risk-prone and maladaptive decision-making characterize a wide range of psychiatric disorders, such as drug addiction and bipolar disorder, but also pertain to such common behaviors as gambling or overextending one's credit. The goal of this proposal is to identify patterns of activity in neural structures involved in evaluating rewards and making decisions between certain and risky outcomes that will inform how risk-preference is represented in the activity of single neurons. Rats will be trained to perform tasks in which they choose between two levers in a test chamber that lead to different reward outcomes (sucrose pellets). In these studies, choices will be based on different reward magnitudes or probabilities of receiving reward. While rats perform these tasks we will record the electrophysiological activity of single neurons in the nucleus accumbens (NAC), which is critical for reward processing, orbitofrontal cortex (OFC), an area thought to be important for making decisions based on reward outcome, and anterior cingulate cortex (ACC), which has been implicated in monitoring conflict and risk. We are interested in how this circuit represents information about absolute reward size (e.g. '3 pellets') to relative value of reward useful for comparison (e.g. 'more than 2'). The long-term goal of our studies is to determine how aberrant signaling in these areas may underlie inaccurate representations of reward which may in turn lead to over-valuation of risky behaviors. PUBLIC HEALTH RELEVANCE: The pervasive problems associated with drug addiction, gambling, or overconsumption (of food or goods) stem from a willingness to engage in behaviors that yield risky outcomes. The goal of this project is to identify how reward expectations- based on the magnitude of the reward and probability of receiving it- are represented in circuitry important for processing rewards and decision-making. These studies have the potential to identify mechanisms underlying risk-preference and therefore new targets for disorders of risky behavior.