D2Ϫ/Ϫ mice exhibited normal CPP, but no cocaine enhancement. In conclusion, dopamine modulation of GABAergic tonic inhibition of D1-and D2-MSNs provides an intrinsic mechanism to differentially affect their excitability in response to psychostimulants and thereby influence their ability to potentiate conditioned reward. Therefore, ␣4␦ GABA A Rs may represent a viable target for the development of novel therapeutics to better understand and influence addictive behaviors.
Despite our ever-changing environment, animals are remarkably adept at selecting courses of action that are predictive of optimal outcomes. While requiring the contribution of a number of brain regions, a vast body of evidence implicates striatal mechanisms of associative learning and action selection to be critical to this ability. While numerous models of striatal-based decision-making have been developed, it is only recently that we have begun to understand the precise contributions of specific subpopulations of striatal neurons. Studies utilizing contemporary cell-type-specific technologies indicate that striatal output pathways play distinct roles in controlling goal-directed and social behaviors. Here we review current models of striatal-based decision-making, discuss recent developments in defining the functional roles of striatal output pathways, and assess how striatal dysfunction may contribute to the etiology of various neuropathologies.
Sensory substitution devices convert live visual images into auditory signals, for example with a web camera (to record the images), a computer (to perform the conversion) and headphones (to listen to the sounds). In a series of three experiments, the performance of one such device (`The vOICe') was assessed under various conditions on blindfolded sighted participants. The main task that we used involved identifying and locating objects placed on a table by holding a webcam (like a flashlight) or wearing it on the head (like a miner's light). Identifying objects on a table was easier with a hand-held device, but locating the objects was easier with a headmounted device. Brightness converted into loudness was less effective than the reverse contrast (dark being loud), suggesting that performance under these conditions (natural indoor lighting, novice users) is related more to the properties of the auditory signal (ie the amount of noise in it) than the cross-modal association between loudness and brightness. Individual differences in musical memory (detecting pitch changes in two sequences of notes) was related to the time taken to identify or recognise objects, but individual differences in self-reported vividness of visual imagery did not reliably predict performance across the experiments. In general, the results suggest that the auditory characteristics of the device may be more important for initial learning than visual associations.
Over the last few decades, advances in human and animal‐based techniques have greatly enhanced our understanding of the neural mechanisms underlying psychiatric disorders. Many of these studies have indicated connectivity between and alterations within basal ganglia structures to be particularly pertinent to the development of symptoms associated with several of these disorders. Here we summarize the connectivity, molecular composition, and function of sites within basal ganglia neurocircuits. Then we review the current literature from both human and animal studies concerning altered basal ganglia function in five common psychiatric disorders: obsessive–compulsive disorder, substance‐related and addiction disorders, major depressive disorder, generalized anxiety disorder, and schizophrenia. Finally, we present a model based upon the findings of these studies that highlights the striatum as a particularly attractive target for restoring normal function to basal ganglia neurocircuits altered within psychiatric disorder patients.
Considerable evidence has demonstrated a critical role for the nucleus accumbens (NAc) in the acquisition and flexibility of behavioral strategies. These processes are guided by the activity of two discrete neuron types, dopamine D1-or D2-receptor expressing medium spiny neurons (D1-/D2-MSNs). Here we used the IntelliCage, an automated group-housing experimental cage apparatus, in combination with a reversible neurotransmission blocking technique to examine the role of NAc D1-and D2-MSNs in the acquisition and reversal learning of a place discrimination task. We demonstrated that NAc D1-and D2-MSNs do not mediate the acquisition of the task, but that suppression of activity in D2-MSNs impairs reversal learning and increased perseverative errors. Additionally, global knockout of the dopamine D2L receptor isoform produced a similar behavioral phenotype to D2-MSN-blocked mice. These results suggest that D2L receptors and NAc D2-MSNs act to suppress the influence of previously correct behavioral strategies allowing transfer of behavioral control to new strategies.
Following repeated pairings, the reinforcing and motivational properties (incentive salience) of a reward can be transferred onto an environmental stimulus which can then elicit conditioned responses, including Pavlovian approach behavior to the stimulus (a sign-tracking response). In rodents, acquisition of sign-tracking in autoshaping paradigms is sensitive to lesions and dopamine D1 receptor antagonism of the nucleus accumbens (NAc) of the ventral striatum. However, currently, the possible roles of dorsal striatal subregions, as well as of the two major striatal neuron types, dopamine D1-/D2-expressing medium spiny neurons (MSNs), in controlling the development of conditioned responses is still unclear and warrants further study. Here, for the first time, we used a transgenic mouse line combined with striatal subregion-specific AAV virus injections to separately express tetanus toxin in D1-/D2- MSNs in the NAc, dorsomedial striatum, and dorsolateral striatum, to permanently block neurotransmission in these neurons during acquisition of an autoshaping task. Neurotransmission blocking of NAc D1-MSNs inhibited the acquisition of sign-tracking responses when the initial conditioned response for each conditioned stimulus presentation was examined, confirming our initial hypothesis. These findings suggest that activity in NAc D1-MSNs contributes to the attribution of incentive salience to conditioned stimuli.
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