Our long-term goal is to understand function in brain circuits which regulate reward-seeking and feeding behaviors. Brain circuits which regulate these behaviors are also implicated in the control of defensive responding elicited by threat or aversive stimuli; however, the manner in which these circuits coordinate competing appetitive and defensive behaviors is not understood. Pharmacological inhibition of neural firing in the medial shell region of the nucleus accumbens (NAcc) has been shown to dramatically elevate food intake in satiated animals and to increase reward-seeking behaviors; conversely, increases in neural firing in this region suppress food intake in hungry animals. The neural firing patterns which underlie these behavioral effects are poorly understood. Electrophysiological experiments in behaving animals have demonstrated that the predominant pattern of neural firing encountered in recordings from the NAcc is of an inhibition of neural firing occurring prior to and during feeding behavior. In the proposed experiments, we will test the hypothesis that NAcc neurons possessing this firing pattern play an important role in the normal control of appetitive and feeding behavior, and that inhibition of firing in these neurons underlies the behavioral effects of pharmacological inhibition of firing in the NAcc shell.
In Specific Aim 1, we will examine the core/shell distribution of this firing pattern to determine if it is predominantly localized to the NAcc shell.
In Specific Aim 2 we will determine if this firing pattern is correlated with appetitive behaviors. Specifically, we will measure and compare firing in this class of neurons during reward seeking to determine 1) if inhibition onset is synchronous with the onset of goal-directed locomotor approach behaviors and 2) if inhibition of neural firing occurs specifically during goal-directed locomotor and operant behaviors.
In Specific Aim 3 we will test the response properties of these NAcc neurons during presentation of an aversive cue, to test the hypothesis that aversive stimuli increase firing rate in these neurons, with the behavioral effect of suppressing appetitive/feeding behaviors when threat stimuli arise. These studies are relevant to human health because they will aid in elucidating function in neural circuits that underlie initiation of goal-directed behavior, and importantly, in identifying neural mechanisms mediating suppression of reward-seeking behaviors. Neural dysfunction in disorders of motivation such as addiction is characterized by an inability to inhibit drug-seeking behaviors despite the damaging consequences of continued drug use. The experiments outlined will aid in understanding function in neural circuits importantly implicated in addiction. Addiction is characterized by an inability to suppress drug-seeking despite the devastating negative consequences of continued drug use. Understanding brain circuits which regulate natural reward-seeking behaviors is an important step in understanding neural changes underlying addiction. The proposed experiments will elucidate function in brain circuits importantly implicated in initiating reward-seeking behavior. ? ? ?
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| Taha, S A; Katsuura, Y; Noorvash, D et al. (2009) Convergent, not serial, striatal and pallidal circuits regulate opioid-induced food intake. Neuroscience 161:718-33 |
