The ventral pallidum: Subregion-specific functional anatomy and roles in motivated behaviors

Abstract

The ventral pallidum (VP) plays a critical role in the processing and execution of motivated behaviors. Yet this brain region is often overlooked in published discussions of the neurobiology of mental health (e.g., addiction, depression). This contributes to a gap in understanding the neurobiological mechanisms of psychiatric disorders. This review is presented to help bridge the gap by providing a resource for current knowledge of VP anatomy, projection patterns and subregional circuits, and how this organization relates to the function of VP neurons and ultimately behavior. For example, ventromedial (VPvm) and dorsolateral (VPdl) VP subregions receive projections from nucleus accumbens shell and core, respectively. Inhibitory GABAergic neurons of the VPvm project to mediodorsal thalamus, lateral hypothalamus, and ventral tegmental area, and this VP subregion helps discriminate the appropriate conditions to acquire natural rewards or drugs of abuse, consume preferred foods, and perform working memory tasks. GABAergic neurons of the VPdl project to subthalamic nucleus and substantia nigra pars reticulata, and this VP subregion is modulated by, and is necessary for, drug-seeking behavior. Additional circuits arise from nonGABAergic neuronal phenotypes that are likely to excite rather than inhibit their targets. These subregional and neuronal phenotypic circuits place the VP in a unique position to process motivationally-relevant stimuli and coherent adaptive behaviors.

The Direct and Indirect Pathways of the Nucleus Accumbens are not What You Think

“…As expected from the canonical circuitry, NAc D1-MSN activation promotes drug-seeking behavior while D2-MSNs had an inhibitory effect. However, other studies have shown that it is the input to the VP, rather than to the VM, which promotes reinstatement of drug-seeking behavior after withdrawal and that the VP itself, unlike its dorsal counterpart the globus pallidus, directly inhibits the thalamus (Root et al, 2015). Thus, the classic circuitry of the reward system was questioned.…”

Optogenetic Inhibition of Ventral Pallidum Neurons Impairs Context-Driven Salt Seeking

“…Animals under sodium deprivation will demonstrate adaptive salt seeking without ever having experienced a concentrated salt solution as pleasant (Fudim, 1978;Robinson and Berridge, 2013). Thus, adaptive salt seeking is regarded as a special form of a nonincremental behavioral adaptation (Dayan and Berridge, 2014).…”

“…Thus, adaptive salt seeking is regarded as a special form of a nonincremental behavioral adaptation (Dayan and Berridge, 2014). For example, following sodium deprivation, rats will im-mediately engage with a cue that had previously been paired with oral infusion of a highly concentrated salt solution (Robinson and Berridge, 2013). Similarly, rats are able to use contextual cues under extinction conditions to flexibly shift their preferences to a salt-paired context, depending on their deprivation state (Stouffer and White, 2005).…”

“…Correlative studies have implicated areas, including the NAc, the ventral pallidum (VP), and the ventral tegmental area in salt seeking, which exhibit heightened activity in response to salt-paired cues following sodium deprivation as though to represent the updated value of those cues (Tindell et al, 2009;Robinson and Berridge, 2013). However, tests demonstrating a causally necessary role of a brain area for appetite-induced salt seeking remain to be conducted.…”

“…Thus, it is unknown whether mechanisms for salt seeking are the same as, or dissociable from, those for the primary motivation to consume salt. One likely candidate for regulating salt-seeking is the VP, a key region for motivated behavior (Cromwell and Berridge, 1993;Smith et al, 2009;Root et al, 2015;Ahrens et al, 2016). Of note, VP neurons do not normally respond to cues predicting an aversive salt outcome (Tindell et al, 2009).…”