Sucrose Reward Research Articles

Early olfactory, but not gustatory processing, is affected by the selection of heritable cognitive phenotypes in honey bee.

Associative learning enables animals to predict rewards or punishments by their associations with predictive stimuli, while non-associative learning occurs without reinforcement. The latter includes latent inhibition (LI), whereby animals learn to ignore an inconsequential 'familiar' stimulus. Individual honey bees display heritable differences in expression of LI. We examined the behavioral and neuronal responses between honey bee genetic lines exhibiting high and low LI. We observed, as in previous studies, that high LI lines learned a familiar odor more slowly than low LI bees. By measuring gustatory responses to sucrose, we determined that perception of sucrose reward was similar between both lines, thereby not contributing to the LI phenotype. We then used extracellular electrophysiology to determine differences in neural responses of the antennal lobe (AL) to familiar and novel odors between the lines. Low LI bees responded significantly more strongly to both familiar and novel odors than the high LI bees, but the lines showed equivalent differences in response to the novel and familiar odors. This work suggests that some effects of genotype are present in early olfactory processing, and those effects could complement how LI is manifested at later stages of processing in brains of bees in the different lines.

Diabetes type 2 risk gene Dusp8 is associated with altered sucrose reward behavior in mice and humans.

BackgroundDusp8 is the first GWAS‐identified gene that is predominantly expressed in the brain and has previously been linked with the development of diabetes type 2 in humans. In this study, we unravel how Dusp8 is involved in the regulation of sucrose reward behavior.MethodsFemale, chow‐fed global Dusp8 WT and KO mice were tested in an observer‐independent IntelliCage setup for self‐administrative sucrose consumption and preference followed by a progressive ratio task with restricted sucrose access to monitor seeking and motivation behavior. Sixty‐three human carriers of the major C and minor T allele of DUSP8 SNP rs2334499 were tested for their perception of food cues by collecting a rating score for sweet versus savory high caloric food.ResultsDusp8 KO mice showed a comparable preference for sucrose, but consumed more sucrose compared to WT mice. In a progressive ratio task, Dusp8 KO females switched to a “trial and error” strategy to find sucrose while control Dusp8 WT mice kept their previously established seeking pattern. Nonetheless, the overall motivation to consume sucrose, and the levels of dopaminergic neurons in the brain areas NAcc and VTA were comparable between genotypes. Diabetes‐risk allele carriers of DUSP8 SNP rs2334499 preferred sweet high caloric food compared to the major allele carriers, rating scores for savory food remained comparable between groups.ConclusionOur data suggest a novel role for Dusp8 in the perception of sweet high caloric food as well as in the control of sucrose consumption and foraging in mice and humans.

Modulatory effects of pheromone on olfactory learning and memory in moths

Pheromones are chemical communication signals known to elicit stereotyped behaviours and/or physiological processes in individuals of the same species, generally in relation to a specific function (e.g. mate finding in moths). However, recent research suggests that pheromones can modulate behaviours, which are not directly related to their usual function and thus potentially affect behavioural plasticity. To test this hypothesis, we studied the possible modulatory effects of pheromones on olfactory learning and memory in Agrotis ipsilon moths, which are well-established models to study sex-pheromones. To achieve this, sexually mature male moths were trained to associate an odour with either a reward (appetitive learning) or punishment (aversive learning) and olfactory memory was tested at medium- and long-term (1 h or 1.5 h, and 24 h). Our results show that male moths can learn to associate an odour with a sucrose reward, as well as a mild electric shock, and that olfactory memory persists over medium- and long-term range. Pheromones facilitated both appetitive and aversive olfactory learning: exposure to the conspecific sex-pheromone before conditioning enhanced appetitive but not aversive learning, while exposure to a sex-pheromone component of a heterospecific species (repellent) facilitated aversive but not appetitive learning. However, this effect was short-term, as medium- and long-term memory were not improved. Thus, in moths, pheromones can modulate olfactory learning and memory, indicating that they contribute to behavioural plasticity allowing optimization of the animal’s behaviour under natural conditions. This might occur through an alteration of sensitization.

Serotonergic Innervations of the Orbitofrontal and Medial-prefrontal Cortices are Differentially Involved in Visual Discrimination and Reversal Learning in Rats.

Cross-species studies have identified an evolutionarily conserved role for serotonin in flexible behavior including reversal learning. The aim of the current study was to investigate the contribution of serotonin within the orbitofrontal cortex (OFC) and medial prefrontal cortex (mPFC) to visual discrimination and reversal learning. Male Lister Hooded rats were trained to discriminate between a rewarded (A+) and a nonrewarded (B−) visual stimulus to receive sucrose rewards in touchscreen operant chambers. Serotonin was depleted using surgical infusions of 5,7-dihydroxytryptamine (5,7-DHT), either globally by intracebroventricular (i.c.v.) infusions or locally by microinfusions into the OFC or mPFC. Rats that received i.c.v. infusions of 5,7-DHT before initial training were significantly impaired during both visual discrimination and subsequent reversal learning during which the stimulus–reward contingencies were changed (A− vs. B+). Local serotonin depletion from the OFC impaired reversal learning without affecting initial discrimination. After mPFC depletion, rats were unimpaired during reversal learning but slower to respond at the stimuli during all the stages; the mPFC group was also slower to learn during discrimination than the OFC group. These findings extend our understanding of serotonin in cognitive flexibility by revealing differential effects within two subregions of the prefrontal cortex in visual discrimination and reversal learning.

Central oxytocin signaling inhibits food reward-motivated behaviors and VTA dopamine responses to food-predictive cues in male rats

Oxytocin potently reduces food intake and is a potential target system for obesity treatment. A better understanding of the behavioral and neurobiological mechanisms mediating oxytocin's anorexigenic effects may guide more effective obesity pharmacotherapy development. The present study examined the effects of central (lateral intracerebroventricular [ICV]) administration of oxytocin in rats on motivated responding for palatable food. Various conditioning procedures were employed to measure distinct appetitive behavioral domains, including food seeking in the absence of consumption (conditioned place preference expression), impulsive responding for food (differential reinforcement of low rates of responding), effort-based appetitive decision making (high-effort palatable vs. low-effort bland food), and sucrose reward value encoding following a motivational shift (incentive learning). Results reveal that ICV oxytocin potently reduces food-seeking behavior, impulsivity, and effort-based palatable food choice, yet does not influence encoding of sucrose reward value in the incentive learning task. To investigate a potential neurobiological mechanism mediating these behavioral outcomes, we utilized in vivo fiber photometry in ventral tegmental area (VTA) dopamine neurons to examine oxytocin's effect on phasic dopamine neuron responses to sucrose-predictive Pavlovian cues. Results reveal that ICV oxytocin significantly reduced food cue-evoked dopamine neuron activity. Collectively, these data reveal that central oxytocin signaling inhibits various obesity-relevant conditioned appetitive behaviors, potentially via reductions in food cue-driven phasic dopamine neural responses in the VTA.

Cocaine and sucrose rewards recruit different seeking ensembles in the nucleus accumbens core.

Poorly regulated reward seeking is a central feature of substance use disorder. Recent research shows that rewarding drug-related experiences induce synchronous activation of a discrete number of neurons in the nucleus accumbens that are causally linked to reward-related contexts. Here we comprehensively characterize the specific ensemble of neurons built through experience that are linked to seeking behavior. We additionally address the question of whether or not addictive drugs usurp the neuronal networks recruited by natural rewards by evaluating cocaine- and sucrose-associated ensembles within the same mouse. We used FosCreERT2/+/Ai14 transgenic mice to tag cells activated by and potentially encoding cocaine and sucrose seeking. We tagged ~1% of neurons in the core subregion of the accumbens (NAcore) activated during cue-induced seeking for cocaine or sucrose. The majority of tagged cells in the seeking ensembles were D1-MSNs, and specifically activated during seeking, not during extinction or when mice remained in the home cage. To compare different reward-specific ensembles within the same mouse, we used a dual cocaine and sucrose self-administration protocol allowing reward-specific seeking. Using this model, we found ~70% distinction between the cells constituting the cocaine- compared to the sucrose-seeking ensemble. Establishing that cocaine recruits an ensemble of NAcore neurons largely distinct from neurons recruited into an ensemble coding for sucrose seeking suggest a finely tuned specificity of ensembles. The findings allow further exploration of the mechanisms that transform reward-based positive reinforcement into maladaptive drug seeking.

Chemogenetic Activation of Mesoaccumbal Gamma-Aminobutyric Acid Projections Selectively Tunes Responses to Predictive Cues When Reward Value Is Abruptly Decreased

BackgroundMesolimbic circuits regulate the attribution of motivational significance to incentive cues that predict reward, yet this network also plays a key role in adapting reward-seeking behavior when the contingencies linked to a cue unexpectedly change. Here, we asked whether mesoaccumbal GABA (gamma-aminobutyric acid) projections enhance adaptive responding to incentive cues of abruptly altered reward value, and whether these effects were distinct from global activation of all ventral tegmental area GABA circuits. MethodsWe used a viral targeting system to chemogenetically activate mesoaccumbal GABA projections in male rats during a novel cue-dependent operant value-shifting task, in which the volume of a sucrose reward associated with a predictive cue is suddenly altered, from the beginning and throughout the session. We compared the results with global activation of ventral tegmental area GABA neurons, which will activate local inhibitory circuits and long loop projections. ResultsWe found that activation of mesoaccumbal GABA projections decreases responding to incentive cues associated with smaller-than-expected rewards. This tuning of behavioral responses was specific to cues associated with smaller-than-expected rewards but did not impact measures related to consuming the reward. In marked contrast, activating all ventral tegmental area GABA neurons resulted in a uniform decrease in responding to incentive cues irrespective of changes in the size of the reward. ConclusionsTargeted activation of mesoaccumbal GABA neurons facilitates adaptation in reward-seeking behaviors. This suggests that these projections may play a very specific role in associative learning processes.

Regional Activity in the Rat Anterior Cingulate Cortex and Insula during Persistence and Quitting in a Physical-Effort Task.

As animals carry out behaviors, particularly costly ones, they must constantly assess whether or not to persist in the behavior or quit. The anterior cingulate cortex (ACC) has been shown to assess the value of behaviors and to be especially sensitive to physical effort costs. Complimentary to these functions, the insula is thought to represent the internal state of the animal including factors such as hunger, thirst, and fatigue. Using a novel weight-lifting task for rats, we characterized the local field potential (LFP) activity of the ACC and anterior insula (AI) during effort expenditure. In the task, male rats are challenged to work for sucrose reward, which costs progressively more effort over time to obtain. Rats are able to quit the task at any point. We found modest shifts in LFP theta (7–9 Hz) activity as the task got progressively more difficult in terms of absolute effort expenditure. However, when the LFP data were analyzed based on the relative progress of the rat toward quitting the task, substantial shifts in LFP power in the theta and gamma (55–100 Hz) frequency bands were observed in ACC and AI. Both ACC and AI theta power decreased as the rats got closer to quitting, while ACC and AI gamma power increased. Furthermore, coherency between ACC and AI in the delta (2–4 Hz) range shifted alongside the performance state of the rat. Overall, we show that ACC and AI LFP activity changes correlate to the relative performance state of rats in an effort-based task.

Thalamic Stimulation Improves Postictal Cortical Arousal and Behavior.

The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

Selective Deficits in Contingency-Driven Ethanol Seeking Following Chronic Ethanol Exposure in Male Mice.

People with alcohol use disorders exhibit an overreliance on habitual response strategies which may result from a history of chronic alcohol exposure. Although habits are defined by behavior that persists despite changes in outcome value and in action-outcome relationships, most research investigating the effects of ethanol exposure on habits has focused only on outcome devaluation. A clear understanding of the effects of chronic alcohol exposure on the ability to flexibly update behavior may provide insight into the behavioral deficits that characterize alcohol use disorders. To dissociate the effects of chronic intermittent ethanol (CIE) exposure on contingency-mediated sucrose versus ethanol seeking, adult male C57Bl/6J mice were assigned to 2 separate experiments. In the first experiment, mice were trained to self-administer ethanol prior to 2 cycles of interleaved CIE exposure by vapor inhalation. In a second experiment, mice were trained to self-administer sucrose and ethanol in separate training sessions prior to 4 cycles of interleaved CIE. The use of contingencies to mediate reward seeking was assessed using a contingency degradation paradigm. In mice trained to self-administer only ethanol, 2weeks of CIE resulted in escalated self-administration. At this time point, CIE-exposed mice, but not air-exposed controls, exhibited ethanol seeking that was insensitive to changes in action-outcome contingency, consistent with habitual ethanol seeking. In mice trained to self-administer ethanol and sucrose rewards in sequential sessions, no escalation in self-administration across 4weeks of CIE was observed. Under these conditions, neither Air- nor CIE-exposed mice reduced ethanol seeking in response to contingency degradation. In contrast, sucrose seeking remained goal-directed. Our results suggest that chronic ethanol exposure impairs contingency-driven ethanol seeking more readily than sucrose-seeking behavior. Further, these findings indicate that the transition from contingency-mediated ethanol seeking occurs more rapidly than for sucrose seeking under similar ethanol exposure conditions.

Nicotine Pretreatment Increases Sensitivity to Reward Devaluation in Extinction

We examined the effects of nicotine preexposure on operant learning and habit formation. Rats were pretreated with 10 doses of 0.4 mg/kg nicotine (n = 9) or saline as a control (n = 9) for 10 consecutive days. Operant training was initiated in which rats learned to nose-poke for a sucrose reward. To examine whether nicotine pretreatment accelerated habitual responding, ad-lib feeding was used to devalue the sucrose reward prior to sessions 1 and 3 of extinction testing. Rats subsequently underwent reacquisition in order to further examine the influence of nicotine pretreatment on operant learning. Preexposure to nicotine did not affect the initial acquisition of the operant response for sucrose or the reacquisition of this response following extinction training. However, nicotine pretreatment expedited extinction learning, but only under conditions of reward devaluation by prefeeding. Because nicotine dosing was terminated 9 days prior to extinction testing, and nicotine was never paired directly with sucrose reinforcement, these results suggest that nicotine exposure has a durable influence on extinction learning.

The Gut-Brain-Microbiome Axis in Bumble Bees.

The brain-gut–microbiome axis is an emerging area of study, particularly in vertebrate systems. Existing evidence suggests that gut microbes can influence basic physiological functions and that perturbations to the gut microbiome can have deleterious effects on cognition and lead to neurodevelopmental disorders. While this relationship has been extensively studied in vertebrate systems, little is known about this relationship in insects. We hypothesized that because of its importance in bee health, the gut microbiota influences learning and memory in adult bumble bees. As an initial test of whether there is a brain-gut–microbiome axis in bumble bees, we reared microbe-inoculated and microbe-depleted bees from commercial Bombus impatiens colonies. We then conditioned experimental bees to associate a sucrose reward with a color and tested their ability to learn and remember the rewarding color. We found no difference between microbe-inoculated and microbe-depleted bumble bees in performance during the behavioral assay. While these results suggest that the brain-gut–microbiome axis is not evident in Bombus impatiens, future studies with different invertebrate systems are needed to further investigate this phenomenon.

Regulation of Pv-specific interneurons in the medial prefrontal cortex and reward-seeking behaviors.

The corticostriatal circuitry and its glutamate-γ-aminobuturic acid (GABA) interactions play an essential role in regulating neuronal excitability during reward-seeking behavior. However, the contribution of GABAergic interneurons in the corticostriatal circuitry remains unclear. To investigate the role of GABAergic interneurons, we focused on parvalbumin-expressing fast-spiking interneurons (Pv-FSI) in the corticostriatal circuitry using the designer receptors exclusively activated by designer drugs approach in a Pv-Cre mouse model. We hypothesize that Pv-FSI activation elicits changes in cortical glutamate levels and reward-seeking behaviors. To determine molecular and behavioral effects of Pv-FSI, we performed microdialysis and operant conditioning tasks for sucrose and alcohol rewards. In addition, we also examined how alcohol reward itself affects Pv-FSI functioning. Interestingly, our microdialysis results demonstrate that alcohol exposure inhibits Pv-FSI functioning in the medial prefrontal cortex (mPFC) and this consequently can regulate glutamate levels downstream in the nucleus accumbens. For sucrose reward-seeking behaviors, Pv-FSI activation in the mPFC increases sucrose self-administration whereas it does not promote alcohol seeking. For alcohol rewards, however, Pv-FSI activation in the mPFC results in increased compulsive head entry in operant chambers during devaluation procedures. Overall, our results suggest that not only do Pv-FSI contribute to changes in the cortical microcircuit and reward-seeking behaviors but also that alcohol affects Pv-FSI neurotransmission. Therefore, Pv-FSI has prompted interest in their role in maintaining a balance in neuronal excitation/inhibition and in regulating reward-seeking processes such as compulsivity, all of which are important factors for excessive alcohol seeking.

Nothing to dance about: unclear evidence for symbolic representations and numerical competence in honeybees. A Comment on: Symbolic representation of numerosity by honeybees (Apis mellifera): matching characters to small quantities.

Nothing to dance about: unclear evidence for symbolic representations and numerical competence in honeybees. A Comment on: Symbolic representation of numerosity by honeybees (Apis mellifera): matching characters to small quantities.

Heightened reward response is associated with HCN2 overexpression in the ventral tegmental area in morphine-sensitized rats.

Morphine sensitization is associated with increased locomotion and stereotypies in rats. This persistent condition has been proposed as a model of manic-like symptoms. Modifications in reward threshold are considered a central feature of mania and have been related to changes in mesocorticolimbic dopaminergic transmission. Thus, to further characterize this model, we investigated reward responses in morphine-sensitized male rats and the mechanisms underlying the behavioral phenotype. In particular, we examined the possible involvement of hyperpolarization-activated cyclic nucleotide-gated channels as they play a critical role in regulating the excitability of dopaminergic neurons. Rats were trained to self-administer sucrose to study whether morphine sensitization affected motivated behavior. Next, the dopaminergic response to sucrose was examined in the nucleus accumbens shell by in vivo microdialysis. To investigate the possible mechanisms underlying the increased dopaminergic transmission in morphine-sensitized rats, HCN2 channel expression levels in mesocorticolimbic regions were analyzed by immunoblotting. Sensitized rats showed an enhanced motivation to work for sucrose that was accompanied by an increased dopaminergic response to sucrose consumption in the nucleus accumbens shell. Moreover, HCN2 expression levels were increased in the ventral tegmental area, suggesting that their increased expression may underpin the enhanced motivation for sucrose reward and nucleus accumbens shell dopaminergic response in sensitized rats. The modified behavioral and dopaminergic reward response observed in sensitized rats supports the suggestion that the condition of morphine sensitization can be regarded as a model of manic symptoms.

Activation of VTA NtsR1 Neurons Promotes Weight Loss Behaviors

Dopamine (DA) neurons in the ventral tegmental area (VTA) modulate motivation to engage in physical activity and food intake, dual behaviors that are disrupted in obesity. However, the functional heterogeneity of VTA DA neurons, and lack of molecular markers to distinguish them, has prevented determination of which DA neurons might be leveraged to support weight loss behaviors. We identified a distinct subset of VTA DA neurons defined by their expression of neurotensin receptor‐1 (NtsR1) and we hypothesized that these “VTA NtsR1 neurons” modulate feeding restraint and physical activity that could support weight loss. To test this hypothesis, we expressed Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) in the VTA NtsR1 neurons of normal weight and diet‐induced obese mice, permitting in vivo activation of VTA NtsR1 neurons by treatment with the DREADD‐ligand clozapine‐N‐oxide (CNO). Acute activation of VTA NtsR1 neurons (24hr) in normal weight and diet‐induced obese mice significantly decreased body weight by reducing food intake and increasing physical activity. Moreover, the weight loss of diet‐induced obese mice was maintained with daily activation of VTA NtsR1 over 7d. Intriguingly, activation of VTA NtsR1 neurons also suppressed how much mice would work to obtain sucrose rewards even when there was high motivation to consume (e.g. in fasted mice or diet‐induced obese mice.) These data suggest that VTA NtsR1 neurons may be useful to support weight loss behavior. Yet, the translational potential of NtsR1 was previously dismissed due to the broad expression of NtsR1 throughout the brain and periphery, and data that systemic NtsR1 agonists cause adverse hypothermia and vasodepressor responses. However, we found that specifically activating VTA NtsR1 neurons does not alter blood pressure, core body temperature or anxiety behavior. Thus, activation of VTA NtsR1 neurons during states of high‐appetitive drive such as fasting and obesity promotes dual behaviors that support weight loss without causing adverse cardiorespiratory effects or stress responses. In the future, strategies to selectively modulating VTA NtsR1 neurons could provide a safe, effective avenue for weight loss.Support or Funding InformationSupported by funding from the National Institutes of Health to Perez‐Bonilla (T32GM092715) and Leinninger (R01‐DK103808)

Insecticide exposure during brood or early-adult development reduces brain growth and impairs adult learning in bumblebees.

For social bees, an understudied step in evaluating pesticide risk is how contaminated food entering colonies affects residing offspring development and maturation. For instance, neurotoxic insecticide compounds in food could affect central nervous system development predisposing individuals to become poorer task performers later-in-life. Studying bumblebee colonies provisioned with neonicotinoid spiked nectar substitute, we measured brain volume and learning behaviour of 3 or 12-day old adults that had experienced in-hive exposure during brood and/or early-stage adult development. Micro-computed tomography scanning and segmentation of multiple brain neuropils showed exposure during either of the developmental stages caused reduced mushroom body calycal growth relative to unexposed workers. Associated with this was a lower probability of responding to a sucrose reward and lower learning performance in an olfactory conditioning test. While calycal volume of control workers positively correlated with learning score, this relationship was absent for exposed workers indicating neuropil functional impairment. Comparison of 3- and 12-day adults exposed during brood development showed a similar degree of reduced calycal volume and impaired behaviour highlighting lasting and irrecoverable effects from exposure despite no adult exposure. Our findings help explain how the onset of pesticide exposure to whole colonies can lead to lag-effects on growth and resultant dysfunction.

Inactivation of the prelimbic cortex attenuates operant responding in both physical and behavioral contexts.

The present experiments aimed to expand our understanding of the role of the prelimbic cortex (PL) in the contextual control of instrumental behavior. Research has previously shown that the PL is involved when the "physical context," or chamber in which an instrumental behavior is trained, facilitates performance of the instrumental response (Trask, Shipman, Green, & Bouton, 2017). Recently, evidence has suggested that when a sequence of two instrumental behaviors is required to earn a reinforcing outcome, the first response (rather than the physical chamber) can be the "behavioral context" for the second response (Thrailkill, Trott, Zerr, and Bouton, 2016). Could the PL also be involved in this kind of contextual control? Here rats first learned a heterogenous behavior chain in which the first response (i.e., pressing a lever or pulling a chain) was cued by a discriminative stimulus and led to a second stimulus which cued a second response (i.e., pulling a chain or pressing a lever); the second response led to a sucrose reward. When the first and second responses were tested in isolation in the training context, pharmacological inactivation of the PL resulted in a reduction of the first response, but not the second response. When the second response was performed in the "context" of the first response (i.e., as part of the behavior chain) however, PL inactivation reduced the second response. Overall, these results support the idea that the PL is important for mediating the effects of a training context on instrumental responding, whether the context is physical or behavioral.

Dimensions of sucrose solutions in the successive negative contrast effect

The consummatory successive negative contrast (cSNC) task typically involves administering food-deprived rats 10 daily 5-min sessions of access to 32 % sucrose (preshift) followed by a few sessions in which the concentration is reduced to 4 % sucrose (postshift). Such sucrose downshift leads to transient suppression of consummatory behavior. Reward downshifts were used to determine whether food-deprived rats treat sucrose solutions as food, because sweetness is a proxy for its caloric content, or as water, because a solution has hydration content. In Experiment 1, a cSNC effect was obtained in food-deprived animals, but not in water-deprived animals. This suggested that food deprivation focused attention on the feeding dimension of sucrose, whereas water deprivation focused attention on the drinking dimension of sucrose. Sucrose downshift results in a greater caloric change than in hydration content because both concentrations continue to provide fluid. Experiments 2 and 3 offered presession access to rewards either before preshift or before postshift sessions, respectively. Consistent with this attentional view, presession access to water (which should focus attention on the feeding dimension), but not to food (which should focus attention on the drinking dimension), suppressed consummatory behavior after a sucrose downshift. Presession access to food, like water deprivation, enhanced the hydration properties of the sucrose solution at the expense of its caloric properties. These results are consistent with an attentional hypothesis according to which the internal state, manipulated via deprivation or presession reward access, determines which dimension of the sucrose reward would control consummatory behavior.

Lesion of striatal patches disrupts habitual behaviors and increases behavioral variability.

Habits are automated behaviors that are insensitive to changes in behavioral outcomes. Habitual responding is thought to be mediated by the striatum, with medial striatum guiding goal-directed action and lateral striatum promoting habits. However, interspersed throughout the striatum are neurochemically differing subcompartments known as patches, which are characterized by distinct molecular profiles relative to the surrounding matrix tissue. These structures have been thoroughly characterized neurochemically and anatomically, but little is known regarding their function. Patches have been shown to be selectively activated during inflexible motor stereotypies elicited by stimulants, suggesting that patches may subserve habitual behaviors. To explore this possibility, we utilized transgenic mice (Sepw1 NP67) preferentially expressing Cre recombinase in striatal patch neurons to target these neurons for ablation with a virus driving Cre-dependent expression of caspase 3. Mice were then trained to press a lever for sucrose rewards on a variable interval schedule to elicit habitual responding. Mice were not impaired on the acquisition of this task, but lesioning striatal patches disrupted behavioral stability across training, and lesioned mice utilized a more goal-directed behavioral strategy during training. Similarly, when mice were forced to omit responses to receive sucrose rewards, habitual responding was impaired in lesioned mice. To rule out effects of lesion on motor behaviors, mice were then tested for impairments in motor learning on a rotarod and locomotion in an open field. We found that patch lesions partially impaired initial performance on the rotarod without modifying locomotor behaviors in open field. This work indicates that patches promote behavioral stability and habitual responding, adding to a growing literature implicating striatal patches in stimulus-response behaviors.