Ventral arkypallidal neurons inhibit accumbal firing to promote reward consumption.

The nucleus accumbens shell (NAcSh) and the ventral pallidum (VP) are critical for reward processing, although the question of how coordinated activity within these nuclei orchestrates reward valuation and consumption remains unclear. Inhibition of NAcSh firing is necessary for reward consumption, but the source of this inhibition remains unknown. Here, we report that a subpopulation of VP neurons, the ventral arkypallidal (vArky) neurons, project back to the NAcSh, where they inhibit NAcSh neurons in vivo in mice. Consistent with this pathway driving reward consumption via inhibition of the NAcSh, calcium activity of vArky neurons scaled with reward palatability (which was dissociable from reward seeking) and predicted the subsequent drinking behavior during a free-access paradigm. Activation of the VP-NAcSh pathway increased ongoing reward consumption while amplifying hedonic reactions to reward. These results establish a pivotal role for vArky neurons in the promotion of reward consumption through modulation of NAcSh firing in a value-dependent manner.

Light-Dependent Electrical Activity in Sea Urchin Tube Feet Cells.

Sea urchins can detect and respond to light, and many species of sea urchins are negatively phototaxic. Light detection is hypothesized to occur via photoreceptors located on sea urchin tube feet, and opsins have been detected in tube feet, spines, and the test. However, the molecular mechanisms underlying light detection are, for the most part, unknown. Individual tube feet disc cells were isolated from purple sea urchins (Strongylocentrotus purpuratus), and the electrical responses of these cells to varying levels of illumination were quantified using the patch clamp technique. No currents were observed under bright illumination, whereas under dark conditions, large, slowly activating currents were consistently observed. Two types of cells were functionally identified based on their responses to darkness. Type I cells sustained currents indefinitely in the dark, whereas Type II cell currents spontaneously decayed after several seconds. The large currents observed were composed of the summation of many smaller events that were characterized by a rapid onset and an exponentially decaying component, which may be indicative of direct vesicular release from the tube feet disc cells in response to the dark conditions.

Ventral pallidal modulation of aversion processing.

Responding to aversive and rewarding stimuli is essential to survival. The ventral pallidum (VP) is a critical node in the mesolimbic network, being the primary output of the nucleus accumbens and projecting to the lateral habenula (LHb) and ventral tegmental area (VTA). The VP is thus poised to modulate the habenula-tegmental circuitry and contribute to processing both rewarding and aversive stimuli. Here, we integrate human functional imaging, behavioral pharmacology in rodents, and recent optogenetic circuit dissection studies of the VP with a focus on the role of the neurochemically-distinct subpopulations in aversion processing. These recent results support a model in which glutamatergic VP neurons play a unique role in aversion processing, while canonical GABAergic VP neurons promote reinforcement and encode the hedonic value of reward. Genetic ablation of glutamatergic, but not GABAergic VP neurons abolishes devaluation of natural reward (sucrose) by pairing with an aversive stimulus (lithium chloride injection). Both of these populations modulate activity throughout the LHb and VTA, which is necessary for expression of adaptive behavior in response to rewarding or aversive stimuli. Future work will address how neuromodulators such as endogenous opioids or dopamine shape function and plasticity within these distinct populations of VP neurons, when these subpopulations are engaged during learning responses to rewarding and aversive stimuli, and how their activity is altered in models of reward-related disorders. Answering these questions will be necessary to understand the basis and ultimately develop targeted therapies for disorders of reward/aversion processing, such as affective, chronic pain and substance use disorders.

Glutamatergic Ventral Pallidal Neurons Modulate Activity of the Habenula-Tegmental Circuitry and Constrain Reward Seeking.

BACKGROUND: The ability to appropriately integrate and respond to rewarding and aversive stimuli is essential for survival. The ventral pallidum (VP) plays a critical role in processing both rewarding and aversive stimuli. However, the VP is a heterogeneous structure, and how VP subpopulations integrate into larger reward networks to ultimately modulate these behaviors is not known. We identify a noncanonical population of glutamatergic VP neurons that play a unique role in responding to aversive stimuli and constraining inappropriate reward seeking. METHODS: Using neurochemical, genetic, and electrophysiological approaches, we characterized glutamatergic VP neurons (n = 4-8 mice/group). We performed patch clamp and in vivo electrophysiology recordings in the lateral habenula, rostromedial tegmental nucleus, and ventral tegmental area to determine the effect of glutamatergic VP neuron activation in these target regions (n = 6-10 mice/group). Finally, we selectively optogenetically stimulated glutamatergic VP neurons in a real-time place preference task and ablated these neurons using a virally expressed caspase to determine their necessity for reward seeking. RESULTS: Glutamatergic VP neurons exhibit little overlap with cholinergic or gamma-aminobutyric acidergic markers, the canonical VP subtypes, and exhibit distinct membrane properties. Glutamatergic VP neurons innervate and increase firing activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons. While nonselective optogenetic stimulation of the VP induced a robust place preference, selective activation of glutamatergic VP neurons induced a place avoidance. Viral ablation of glutamatergic VP neurons increased reward responding and abolished taste aversion to sucrose. CONCLUSIONS: Glutamatergic VP neurons constitute a noncanonical subpopulation of VP neurons. These glutamatergic VP neurons increase activity of the lateral habenula, rostromedial tegmental nucleus, and gamma-aminobutyric acidergic ventral tegmental area neurons and adaptively constrain reward seeking.

The Influence of Assay Design, Blinding, and Gymnema sylvestre on Sucrose Detection by Humans.

The detection and grading of tastes corresponding to different taste modalities can be tested in engaging laboratory sessions using students themselves as test subjects. This article describes a series of experiments in which data pertaining to the detection of salty and sweet tastes are obtained, and the ability of the herb Gymnema sylvestre to disrupt the detection of sucrose is quantified. The effects of blinding and different assay designs on EC50 estimation are also investigated. The data obtained allow for substantial data analysis, including non-linear regression using fixed and free parameters to quantify dose-response relationships, and the use of often under-utilized permutation tests to determine significant differences when the underlying data display heteroscedasticity.