Neuroscience
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Patients with Parkinson's disease (PD) show cognitive impairments, including difficulty in shifting attention between perceptual dimensions of complex stimuli. Inactivation of the subthalamic nucleus (STN) has been shown to be effective in ameliorating the motor abnormalities associated with striatal dopamine (DA) depletion, but it is possible that STN inactivation might result in additional, perhaps attentional, deficits. This study examined the effects of: DA depletion from the dorsomedial striatum (DMS); lesions of the STN area; and the effects of the two lesions together, on the ability to shift attentional set in the rat. ⋯ Large bilateral ibotenic acid lesions centered on the STN resulted in an increase in trials to criterion in the initial stages, but learning rate improved within the session. There was no evidence of a 'cost' of set-shifting - the ED stage was completed in fewer trials than the ID stage - and neither was there a cost of reversal learning. Strikingly, combined lesions of both regions did not resemble the effects of either lesion alone and resulted in no apparent deficits.
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Cognitive biases may play a significant role in disorders of decision making such as pathological gambling and addiction. Understanding the neurobiology of these biases could lead to more effective pharmacological and therapeutic treatments for disorders in which aberrant decision making is prominent. The rodent Betting Task (rBT) was designed to measure one commonly observed decision-making heuristic in rodents, namely "escalation of commitment" in which subjects become more risk averse as the stakes increase, even if the odds of success remain constant. ⋯ In the current study, the orbitofrontal (OFC), prelimbic (PrL), and infralimbic cortex (IL) were inactivated to evaluate the contributions made by these regions to choice behavior on the rBT. Inactivation of the OFC (but not the IL or the PrL) selectively ameliorated the risk-averse choice pattern characteristic of wager-sensitive animals. This finding suggests that the OFC may have a relatively unique role in promoting this type of non-normative decision-making under uncertainty, an effect that is potentially related to its role in representing the subjective value of reinforcing outcomes.
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The lateral habenula (LHb) is known to play an important role in signaling aversive or adverse events that have happened or are predicted by cues under Pavlovian conditions. In rodents, it is also required for behavioral flexibility when changes in reward outcomes signal that strategies should be changed. It is not known whether the LHb also controls appetitive behaviors when an animal is able to utilize external cues proactively to guide upcoming decisions. ⋯ Once a correct choice was made in a given block, LHb inactivated rats did not make more errors than controls. A control study revealed that the LHb is not required for tone or reward magnitude discrimination per se. These results demonstrate for the first time that the LHb contributes to behavioral flexibility through utilizing both proactive and retroactive information when performing appetitive tasks.
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Amphetamine and other drugs of abuse have both short-term and long-lasting effects on brain function, and drug sensitization paradigms often result in chronic impairments in behavioral flexibility. Here we show that acute amphetamine administration temporarily renders rats less sensitive to reward omission, as revealed by a decrease in lose-shift responding during a binary choice task. Intracerebral infusions of amphetamine into the ventral striatum did not affect lose-shift responding but did increase impulsive behavior in which rats chose to check both reward feeders before beginning the next trial. ⋯ These treatments did not affect choices on trials following reward delivery (i.e. win-stay responding), and sensitization increased spine density in the sensorimotor striatum. The dichotomous effects of amphetamine on short-term and long-term loss sensitivity, and the null effect on win-stay responding, are consistent with a shift of behavioral control to the sensorimotor striatum after drug sensitization. These data provide a new demonstration of such a shift in a novel task unrelated to drug administration, and suggests that the dominance of sensorimotor control persists over many hundreds of trials after sensitization.
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The prefrontal cortex (PFC) is critical for the ability to flexibly adapt established patterns of behavior in response to a change in environmental contingencies. Impaired behavioral flexibility results in maladaptive strategies such as perseveration on response options that no longer produce a desired outcome. Pharmacological manipulations of prefrontal cortical GABAergic signaling modulate behavioral flexibility in animal models, and prefrontal cortical interneuron dysfunction is implicated in impaired behavioral flexibility that accompanies neuropsychiatric disease. ⋯ Among aged rats, GABA(B) receptor expression in the medial prefrontal cortex (mPFC) was strongly correlated with set shifting, such that lower expression was associated with worse performance. Subsequent experiments showed that intra-mPFC administration of the GABA(B) receptor agonist baclofen enhanced set shifting performance in aged rats. These data directly link GABAergic signaling via GABA(B) receptors to impaired behavioral flexibility associated with normal aging.