Limbic and cortical information processing in the nucleus accumbens

Abstract

The nucleus accumbens regulates goal-directed behaviors by integrating information from limbic structures and the prefrontal cortex. Here, we review recent studies in an attempt to provide an integrated view of the control of information processing in the nucleus accumbens in terms of the regulation of goal-directed behaviors and how disruption of these functions might underlie the pathological states in drug addiction and other psychiatric disorders. We propose a model that could account for the results of several studies investigating limbic-system interactions in the nucleus accumbens and their modulation by dopamine and provide testable hypotheses for how these might relate to the pathophysiology of major psychiatric disorders.

Figure 1

A model of input integration within the NAcc. (a) When a novel situation is encountered, although excitatory inputs from sets of neurons (black circles) in regions 1, 2 and 3 (e.g. the hippocampus, amygdala and PFC) are recruited, the non-coincident inputs fail to bring NAcc neurons to threshold (gray circles) and, therefore, there is no spike firing in NAcc neurons and no output. (b) By contrast, when responding to a well-learned situation, a specific pattern of coincident inputs into the NAcc evokes spike firing in a set of neurons that codes for a previously learned behavioral response known to be effective at achieving a goal. (c) Under different behavioral conditions, a distinct pattern of coincident inputs produces a unique pattern of NAcc output leading to a different effective behavioral outcome.

Figure 2

A schematic diagram illustrating how tonic and phasic DA release are proposed to modulate PFC and hippocampal glutamatergic inputs through D₂ receptors located presynaptically on PFC terminals and D₁ receptors located postsynaptically on NAcc neurons, respectively. Extracellular tonic DA levels are controlled by VP inputs that control DA-neuron population activity, whereas phasic DA release within the synaptic cleft is regulated by PPTg-mediated release of glutamate onto DA neurons in the VTA. Phasic DA release is then removed by reuptake into DA terminals via the DA transporter (DAT).

Figure 3

DA regulation of limbic and cortical information processing in the NAcc. (a) Simplified anatomical organization of the hippocampal and PFC input integration and VTA DA afferents into the NAcc. (b) When animals encounter unexpected rewards or signals predicting rewards, phasic DA release is evoked, facilitating hippocampus drives into NAcc through D₁-receptor stimulation. In this condition, NAcc activity is facilitated, which, in turn, suppresses the VP. As a consequence, tonic inhibition of DA neurons is removed, thereby facilitating tonic DA release in the NAcc, which, in turn, attenuates PFC input via D₂-receptor stimulation. Therefore, information-irrelevant cortical inputs are filtered out and only highly salient information sent out from the PFC is capable of activating the thalamo-cortico-basal ganglia loop; such feedback information from the thalamus to the PFC would then selectively reinforce this specific PFC–NAcc afferent drive. This process, therefore, mediates learning process of a response strategy for reward-seeking behavior. (c) By contrast, when animals encounter a situation that expected rewards are omitted, suppression of tonic firing of DA neurons and tonic release of DA in the NAcc occur, which strengthen PFC inputs into the NAcc via decreased stimulation of D₂ receptors. This PFC input facilitation mediates inhibition of reinforced reward-seeking behavior guided by hippocampus–NAcc information processing. Abbreviation: HPC, hippocampus.