Dissociable encoding of motivated behavior by parallel thalamo-striatal projections.

The successful pursuit of goals requires the coordinated execution and termination of actions that lead to positive outcomes. This process relies on motivational states that are guided by internal drivers, such as hunger or fear. However, the mechanisms by which the brain tracks motivational states to shape instrumental actions are not fully understood. The paraventricular nucleus of the thalamus (PVT) is a midline thalamic nucleus that shapes motivated behaviors via its projections to the nucleus accumbens (NAc)1,2,3,4,5,6,7,8 and monitors internal state via interoceptive inputs from the hypothalamus and brainstem.3,9,10,11,12,13,14 Recent studies indicate that the PVT can be subdivided into two major neuronal subpopulations, namely PVTD2(+) and PVTD2(-), which differ in genetic identity, functionality, and anatomical connectivity to other brain regions, including the NAc.4,15,16 In this study, we used fiber photometry to investigate the in vivo dynamics of these two distinct PVT neuronal types in mice performing a foraging-like behavioral task. We discovered that PVTD2(+) and PVTD2(-) neurons encode the execution and termination of goal-oriented actions, respectively. Furthermore, activity in the PVTD2(+) neuronal population mirrored motivation parameters such as vigor and satiety. Similarly, PVTD2(-) neurons also mirrored some of these parameters, but to a much lesser extent. Importantly, these features were largely preserved when activity in PVT projections to the NAc was selectively assessed. Collectively, our results highlight the existence of two parallel thalamo-striatal projections that participate in the dynamic regulation of goal pursuits and provide insight into the mechanisms by which the brain tracks motivational states to shape instrumental actions.

Mindfulness-Oriented Recovery Enhancement for Veterans and Military Personnel on Long-Term Opioid Therapy for Chronic Pain: A Randomized Clinical Trial.

OBJECTIVE: This randomized clinical trial evaluated the efficacy of Mindfulness-Oriented Recovery Enhancement (MORE) among past and present U.S. military personnel with prescriptions for long-term opioid therapy for chronic pain. METHODS: In this clinical trial, 230 past and present military personnel with prescriptions for long-term opioid therapy were randomized in a 1:1 ratio to MORE or supportive psychotherapy (initially delivered in person and then via videoconferencing after the onset of the COVID-19 pandemic). Primary outcomes were chronic pain, measured by the Brief Pain Inventory, and aberrant drug-related behaviors, measured by the Current Opioid Misuse Measure, through 8 months of follow-up. Opioid dose was a key secondary outcome. Other outcomes included psychiatric symptoms, catastrophizing, positive affect, ecological momentary assessments of opioid craving, and opioid attentional bias. RESULTS: MORE was superior to supportive psychotherapy through the 8-month follow-up in reducing pain-related functional interference, pain severity, and opioid dose. MORE reduced daily opioid dose by 20.7%, compared with a dose reduction of 3.9% with supportive psychotherapy. Although there was no overall between-group difference in opioid misuse, the in-person MORE intervention outperformed supportive psychotherapy for reducing opioid misuse. MORE reduced anhedonia, pain catastrophizing, craving, and opioid attentional bias and increased positive affect to a greater extent than supportive psychotherapy. MORE also modulated therapeutic processes, including mindful reinterpretation of pain sensations, nonreactivity, savoring, positive attention, and reappraisal. CONCLUSIONS: Among past and present U.S. military personnel, MORE led to sustained decreases in chronic pain, opioid use, craving, and opioid cue reactivity. MORE facilitated opioid dose reduction while preserving adequate pain control and preventing mood disturbances, suggesting its utility for safe opioid tapering.

Hypothalamic CRF neurons facilitate brain reward function.

Aversive stimuli activate corticotropin-releasing factor (CRF)-expressing neurons in the paraventricular nucleus of hypothalamus (PVNCRF neurons) and other brain stress systems to facilitate avoidance behaviors. Appetitive stimuli also engage the brain stress systems, but their contributions to reward-related behaviors are less well understood. Here, we show that mice work vigorously to optically activate PVNCRF neurons in an operant chamber, indicating a reinforcing nature of these neurons. The reinforcing property of these neurons is not mediated by activation of the hypothalamic-pituitary-adrenal (HPA) axis. We found that PVNCRF neurons send direct projections to the ventral tegmental area (VTA), and selective activation of these projections induced robust self-stimulation behaviors, without activation of the HPA axis. Similar to the PVNCRF cell bodies, self-stimulation of PVNCRF-VTA projection was dramatically attenuated by systemic pretreatment of CRF receptor 1 or dopamine D1 receptor (D1R) antagonist and augmented by corticosterone synthesis inhibitor metyrapone, but not altered by dopamine D2 receptor (D2R) antagonist. Furthermore, we found that activation of PVNCRF-VTA projections increased c-Fos expression in the VTA dopamine neurons and rapidly triggered dopamine release in the nucleus accumbens (NAc), and microinfusion of D1R or D2R antagonist into the NAc decreased the self-stimulation of these projections. Together, our findings reveal an unappreciated role of PVNCRF neurons and their VTA projections in driving reward-related behaviors, independent of their core neuroendocrine functions. As activation of PVNCRF neurons is the final common path for many stress systems, our study suggests a novel mechanism underlying the positive reinforcing effect of stressful stimuli.

The cognitive (lateral) hypothalamus.

Despite the physiological complexity of the hypothalamus, its role is typically restricted to initiation or cessation of innate behaviors. For example, theories of lateral hypothalamus argue that it is a switch to turn feeding 'on' and 'off' as dictated by higher-order structures that render when feeding is appropriate. However, recent data demonstrate that the lateral hypothalamus is critical for learning about food-related cues. Furthermore, the lateral hypothalamus opposes learning about information that is neutral or distal to food. This reveals the lateral hypothalamus as a unique arbitrator of learning capable of shifting behavior toward or away from important events. This has relevance for disorders characterized by changes in this balance, including addiction and schizophrenia. Generally, this suggests that hypothalamic function is more complex than increasing or decreasing innate behaviors.

Effectiveness of behavioral activation and mindfulness in increasing reward sensitivity and reducing depressive symptoms - A randomized controlled trial.

Reward insensitivity is a potential key mechanism regarding the maintenance of depression. However, there is a lack of research examining and comparing the effectiveness of different psychological interventions in modifying reward insensitivity. This four-arm randomized controlled trial (RCT) investigated a two-week online intervention. After screening for eligibility, a total of 336 participants were randomized, and 224 participated per-protocol. Participants were assigned to either a) behavioral activation, b) mindfulness and gratitude, c) a combination of both, or d) a waitlist control condition. They received videos and implemented daily exercises. Reward sensitivity and depressive symptoms served as primary outcomes. Behavioral activation and mindfulness significantly improved depressive symptoms and reward sensitivity. However, the effects of behavioral activation were not superior. The combination treatment versus the waiting group was insignificant regarding reward insensitivity. Explorative analyses revealed that all intervention groups reduced anhedonia substantially. Our findings imply that brief online interventions with behavioral activation and mindfulness-based approaches can impact reward insensitivity, while effects for a combination were less clear. Nonetheless, our results do not allow us to infer the differential effectiveness of the interventions. There is a clear need for treatments better targeting maintaining factors of depression, such as reward insensitivity. Clinical trial registration number: NCT05402150.

Cognitive and sensory expectations independently shape musical expectancy and pleasure.

Expectation is crucial for our enjoyment of music, yet the underlying generative mechanisms remain unclear. While sensory models derive predictions based on local acoustic information in the auditory signal, cognitive models assume abstract knowledge of music structure acquired over the long term. To evaluate these two contrasting mechanisms, we compared simulations from four computational models of musical expectancy against subjective expectancy and pleasantness ratings of over 1000 chords sampled from 739 US Billboard pop songs. Bayesian model comparison revealed that listeners' expectancy and pleasantness ratings were predicted by the independent, non-overlapping, contributions of cognitive and sensory expectations. Furthermore, cognitive expectations explained over twice the variance in listeners' perceived surprise compared to sensory expectations, suggesting a larger relative importance of long-term representations of music structure over short-term sensory-acoustic information in musical expectancy. Our results thus emphasize the distinct, albeit complementary, roles of cognitive and sensory expectations in shaping musical pleasure, and suggest that this expectancy-driven mechanism depends on musical information represented at different levels of abstraction along the neural hierarchy. This article is part of the theme issue 'Art, aesthetics and predictive processing: theoretical and empirical perspectives'.

Imager-A mobile health mental imagery-based ecological momentary intervention targeting reward sensitivity: A randomized controlled trial.

Robust reward sensitivity may help preserve mental well-being in the face of adversity and has been proposed as a key stress resilience factor. Here, we present a mobile health application, "Imager," which targets reward sensitivity by training individuals to create mental images of future rewarding experiences. We conducted a two-arm randomized controlled trial with 95 participants screened for reward sensitivity. Participants in the intervention group received an ecological momentary intervention-Imager, which encouraged participants to create mental images of rewarding events for 1 week. The control group participants received only ecological momentary assessment, without the instruction to generate mental images. Adherence to Imager was high; participants in the intervention group engaged in 88% of the planned activities. In the follow-up assessment, the intervention group reported less mental health symptoms, mainly in depression (ß = -0.34, df = 93, p = .004) and less perceived stress (ß = -0.18, df = 93, p = .035), than control group participants and compared with the baseline assessment. Our results show the positive effects of Imager on mental health symptoms. The encouraging effects of the app on mental health outcomes may lead to greater use of ecological momentary interventions in the clinical preventive practice of affective disorders.

Direct cortical inputs to hippocampal area CA1 transmit complementary signals for goal-directed navigation.

The subregions of the entorhinal cortex (EC) are conventionally thought to compute dichotomous representations for spatial processing, with the medial EC (MEC) providing a global spatial map and the lateral EC (LEC) encoding specific sensory details of experience. Yet, little is known about the specific types of information EC transmits downstream to the hippocampus. Here, we exploit in vivo sub-cellular imaging to record from EC axons in CA1 while mice perform navigational tasks in virtual reality (VR). We uncover distinct yet overlapping representations of task, location, and context in both MEC and LEC axons. MEC transmitted highly location- and context-specific codes; LEC inputs were biased by ongoing navigational goals. However, during tasks with reliable reward locations, the animals' position could be accurately decoded from either subregion. Our results revise the prevailing dogma about EC information processing, revealing novel ways spatial and non-spatial information is routed and combined upstream of the hippocampus.

Cannabidiol tempers alcohol intake and neuroendocrine and behavioural correlates in alcohol binge drinking adolescent rats. Focus on calcitonin gene-related peptide's brain levels.

Alcohol binge drinking is common among adolescents and may challenge the signalling systems that process affective stimuli, including calcitonin gene-related peptide (CGRP) signalling. Here, we employed a rat model of adolescent binge drinking to evaluate reward-, social- and aversion-related behaviour, glucocorticoid output and CGRP levels in affect-related brain regions. As a potential rescue, the effect of the phytocannabinoid cannabidiol was explored. Adolescent male rats underwent the intermittent 20% alcohol two-bottle choice paradigm; at the binge day (BD) and the 24 h withdrawal day (WD), we assessed CGRP expression in medial prefrontal cortex (mPFC), nucleus accumbens (NAc), amygdala, hypothalamus and brainstem; in addition, we evaluated sucrose preference, social motivation and drive, nociceptive response, and serum corticosterone levels. Cannabidiol (40 mg/kg, i.p.) was administered before each drinking session, and its effect was measured on the above-mentioned readouts. At BD and WD, rats displayed decreased CGRP expression in mPFC, NAc and amygdala; increased CGRP levels in the brainstem; increased response to rewarding- and nociceptive stimuli and decreased social drive; reduced serum corticosterone levels. Cannabidiol reduced alcohol consumption and preference; normalised the abnormal corticolimbic CGRP expression, and the reward and aversion-related hyper-responsivity, as well as glucocorticoid levels in alcohol binge-like drinking rats. Overall, CGRP can represent both a mediator and a target of alcohol binge-like drinking and provides a further piece in the intricate puzzle of alcohol-induced behavioural and neuroendocrine sequelae. CBD shows promising effects in limiting adolescent alcohol binge drinking and rebalancing the bio-behavioural abnormalities.

The effects of an 8-week mindful eating intervention on anticipatory reward responses in striatum and midbrain.

Introduction: Accumulating evidence suggests that increased neural responses during the anticipation of high-calorie food play an important role in the tendency to overeat. A promising method for counteracting enhanced food anticipation in overeating might be mindfulness-based interventions (MBIs). However, the neural mechanisms by which MBIs can affect food reward anticipation are unclear. In this randomized, actively controlled study, the primary objective was to investigate the effect of an 8-week mindful eating intervention on reward anticipation. We hypothesized that mindful eating would decrease striatal reward anticipation responses. Additionally, responses in the midbrain-from which the reward pathways originate-were explored. Methods: Using functional magnetic resonance imaging (fMRI), we tested 58 healthy participants with a wide body mass index range (BMI: 19-35 kg/m2), motivated to change their eating behavior. During scanning they performed an incentive delay task, measuring neural reward anticipation responses to caloric and monetary cues before and after 8 weeks of mindful eating or educational cooking (active control). Results: Compared with the educational cooking intervention, mindful eating affected neural reward anticipation responses, with reduced caloric relative to monetary reward responses. This effect was, however, not seen in the striatum, but only in the midbrain. The secondary objective was to assess temporary and long-lasting (1 year follow-up) intervention effects on self-reported eating behavior and anthropometric measures [BMI, waist circumference, waist-to-hip-ratio (WHR)]. We did not observe effects of the mindful eating intervention on eating behavior. Instead, the control intervention showed temporary beneficial effects on BMI, waist circumference, and diet quality, but not on WHR or self-reported eating behavior, as well as long-lasting increases in knowledge about healthy eating. Discussion: These results suggest that an 8-week mindful eating intervention may have decreased the relative salience of food cues by affecting midbrain but not striatal reward responses, without necessarily affecting regular eating behavior. However, these exploratory results should be verified in confirmatory research.The primary and secondary objectives of the study were registered in the Dutch Trial Register (NTR): NL4923 (NTR5025).

A novel perspective on the role of nucleus accumbens neurons in encoding associative learning.

The nucleus accumbens (NAc) has been considered a key brain region for encoding reward/aversion and cue-outcome associations. These processes are encoded by medium spiny neurons that express either dopamine receptor D1 (D1-MSNs) or D2 (D2-MSNs). Despite the well-established role of NAc neurons in encoding reward/aversion, the underlying processing by D1-/D2-MSNs remains largely unknown. Recent electrophysiological, optogenetic and calcium imaging studies provided insight on the complex role of D1- and D2-MSNs in these behaviours and helped to clarify their involvement in associative learning. Here, we critically discuss findings supporting an intricate and complementary role of NAc D1- and D2-MSNs in associative learning, emphasizing the need for additional studies in order to fully understand the role of these neurons in behaviour.

Stress to inflammation and anhedonia: Mechanistic insights from preclinical and clinical models.

Anhedonia, as evidenced by impaired pleasurable response to reward, reduced reward motivation, and/or deficits in reward-related learning, is a common feature of depression. Such deficits in reward processing are also an important clinical target as a risk factor for depression onset. Unfortunately, reward-related deficits remain difficult to treat. To address this gap and inform the development of effective prevention and treatment strategies, it is critical to understand the mechanisms that drive impairments in reward function. Stress-induced inflammation is a plausible mechanism of reward deficits. The purpose of this paper is to review evidence for two components of this psychobiological pathway: 1) the effects of stress on reward function; and 2) the effects of inflammation on reward function. Within these two areas, we draw upon preclinical and clinical models, distinguish between acute and chronic effects of stress and inflammation, and address specific domains of reward dysregulation. By addressing these contextual factors, the review reveals a nuanced literature which might be targeted for additional scientific inquiry to inform the development of precise interventions.

Auditory Personalization of EMDR Treatment to Relieve Trauma Effects: A Feasibility Study [EMDR+].

According to the WHO (World Health Organization), Eye Movement Desensitization and Reprocessing (EMDR) is an elective therapy to treat people with post-traumatic stress disorders (PTSD). In line with the personalization of therapeutic strategies, through this pilot study, we assessed in people suffering from the effects of trauma the feasibility, safety, acceptance, and efficacy of EMDR enriched with sound stimulation (by administering neutral sounds synchronized with the guided bilateral alternating stimulation of the gaze) and musical reward (musical listening based on the patients' predisposition and personal tastes). Feasibility, quantified by the number of patients who completed the treatment, was excellent as this was the case in 12 out of the 12 enrolled people with psychological trauma. Safety and acceptance, assessed by self-compiled questionnaires, were excellent, with an absence of side effects and high satisfaction. Efficacy, quantified by the number of EMDR treatment sessions required to reach the optimal scores on the Subjective Units of Disturbance (SUD) and Validity of Cognition (VOC) scales typical of EMDR protocols, revealed an average duration of 8.5 (SD 1.2) sessions, which is well below the 12 sessions considered a standard EMDR treatment duration. EMDR+ appears to be a relevant personalization of EMDR, particularly in music-sensitive people, consolidating the therapeutic alliance through a multisensory communicative bond for trauma treatment.

Beyond Mor: Can Induction of Dopamine Homeostasis Along with Electrotherapy Attenuate the Opioid Crisis?

One important area for consideration especially in terms of combating the ongoing never ending opioid crisis, relates to novel newer assessments for all addictive behaviors both substance and non-substance behaviors (RDS). It is very important to identify early in one's life the possibility of, because of known DNA antecedents, the presence of pre-addiction. The development of the Genetic Addiction Risk Severity (GARS) test, Blum's group believes that this type of testing should be the "standard of care" following additional studies. Understandably that while polymorphisms in the Mu-Opioid receptor (MOR) is of real concern in terms of setting people up for predisposition to opioid dependence, the genetic and epigenetic status of dopaminergic function must be considered as well. While this sounds bold (which it is) the results should be protected by the G.I. N. A. law enacted in the USA in 2011. One avenue of further investigation, instead of providing powerful opioids for opioid dependence, is to seek out non-addictive alternatives. Accordingly, other non-addictive modalities including genetic guided KB220 (amino-acid-enkephalinase-N-acetylcysteine-NAD), non-invasive rTMS for psychiatry and pain, epigenetic remodeling, gene edits, non-invasive H-wave for pain management and enhanced functionality, brain spotting, cognitive behavioral therapy awarenesss integration therapy, NUCALM, trauma therapy, awareness tools, genograms, exercise, sports, fitness programs (one hour per day), light therapy and even laughing therapy as well as any other known modalities that can induce reward symmetry. While the short term use of opioids for opioid dependence to reduce harm is certainly acceptable, clinicians should consider a better long-term plan.

Mindfulness-Oriented Recovery Enhancement remediates anhedonia in chronic opioid use by enhancing neurophysiological responses during savoring of natural rewards.

BACKGROUND: Neuropsychopharmacologic effects of long-term opioid therapy (LTOT) in the context of chronic pain may result in subjective anhedonia coupled with decreased attention to natural rewards. Yet, there are no known efficacious treatments for anhedonia and reward deficits associated with chronic opioid use. Mindfulness-Oriented Recovery Enhancement (MORE), a novel behavioral intervention combining training in mindfulness with savoring of natural rewards, may hold promise for treating anhedonia in LTOT. METHODS: Veterans receiving LTOT (N = 63) for chronic pain were randomized to 8 weeks of MORE or a supportive group (SG) psychotherapy control. Before and after the 8-week treatment groups, we assessed the effects of MORE on the late positive potential (LPP) of the electroencephalogram and skin conductance level (SCL) during viewing and up-regulating responses (i.e. savoring) to natural reward cues. We then examined whether these neurophysiological effects were associated with reductions in subjective anhedonia by 4-month follow-up. RESULTS: Patients treated with MORE demonstrated significantly increased LPP and SCL to natural reward cues and greater decreases in subjective anhedonia relative to those in the SG. The effect of MORE on reducing anhedonia was statistically mediated by increases in LPP response during savoring. CONCLUSIONS: MORE enhances motivated attention to natural reward cues among chronic pain patients on LTOT, as evidenced by increased electrocortical and sympathetic nervous system responses. Given neurophysiological evidence of clinical target engagement, MORE may be an efficacious treatment for anhedonia among chronic opioid users, people with chronic pain, and those at risk for opioid use disorder.

Restructuring reward: A pilot study to enhance natural reward response in adults with cannabis use disorder.

BACKGROUND: Hedonic dysregulation is a core mechanism of addiction. There is a dearth of research on hedonic dysregulation in cannabis use disorder (CUD). The current study tested whether personalized scripted imagery may be an efficacious approach to remediate reward functioning in adults with CUD. METHODS: Adults with CUD (n=10) and non-CUD controls (n=12) completed a single session personalized scripted imagery procedure. Non-drug (i.e. natural) reward and neutral scripts were transcribed and participants listened to the scripts in counterbalanced order. Primary outcomes included positive affect (PA), galvanic skin response (GSR), and cortisol and were assessed at four timepoints. Mixed effects models were used to compare between and within subject effects. RESULTS: Mixed effects models revealed a Condition (reward vs. neutral) X Group (CUD vs. control) interaction (p=0.01) on PA response, indicating blunted PA response to the neutral script relative to the reward script in CUD participants. Likewise, GSR response in CUD participants was decreased in response to the neutral script relative to the reward script (p=0.034; interaction n.s.). An interaction effect of Group X PA on cortisol response was found (p=.036) indicating that cortisol was positively correlated with PA in healthy control participants, but not CUD participants. CONCLUSIONS: Adults with CUD may demonstrate acute deficits in hedonic tone under neutral conditions relative to healthy controls. Personalized scripted imagery may be an efficacious tool to remediate hedonic dysregulation in CUD. Cortisol may play a role in healthy positive affect regulation warranting further investigation.

Conflicting constraints on male mating success shape reward size in pollen-rewarding plants.

PREMISE: Pollen-rewarding plants face two conflicting constraints: They must prevent consumptive emasculation while remaining attractive to pollen-collecting visitors. Small pollen packages (the quantity of pollen available in a single visit) may discourage visitors from grooming (reducing consumptive loss) but may also decrease a plant's attractiveness to pollen-collecting visitors. What package size best balances these two constraints? METHODS: We modeled the joint effects of pollinators' grooming behaviors and package size preferences on the optimal package size (i.e., the size that maximizes pollen donation). We then used this model to examine Darwin's conjecture that selection should favor increased pollen production in pollen-rewarding plants. RESULTS: When package size preferences are weak, minimizing package size reduces grooming losses and should be favored (as in previous theoretical studies). Stronger preferences select for larger packages despite the associated increase to grooming loss because loss associated with nonremoval of smaller packages is even greater. Total pollen donation increases with production (as Darwin suggested). However, if floral visitation declines or packages size preference increases with overall pollen availability, the fraction of pollen donated may decline as per-plant pollen production increases. Hence, increasing production may result in diminishing returns. CONCLUSIONS: Pollen-rewarding plants can balance conflicting constraints on pollen donation by producing intermediate-sized pollen packages. Strictly pollen-rewarding plants may have responded to past selection to produce more pollen in total, but diminishing returns may limit the strength of that selection.

Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study.

INTRODUCTION: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. METHODS: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. RESULTS: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. CONCLUSION: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

The rostral intralaminar nuclear complex of the thalamus supports striatally mediated action reinforcement.

The dorsal striatum (DS) mediates the selection of actions for reward acquisition necessary for survival. Striatal pathology contributes to several neuropsychiatric conditions, including aberrant selection of actions for specific rewards in addiction. A major source of glutamate driving striatal activity is the rostral intralaminar nuclei (rILN) of the thalamus. Yet, the information that is relayed to the striatum to support action selection is unknown. Here, we discovered that rILN neurons projecting to the DS are innervated by a range of cortical and subcortical afferents and that rILN→DS neurons stably signaled at two time points in mice performing an action sequence task reinforced by sucrose reward: action initiation and reward acquisition. In vivo activation of this pathway increased the number of successful trials, whereas inhibition decreased the number of successful trials. These findings illuminate a role for the rostral intralaminar nuclear complex in reinforcing actions.

Activation of the central but not the medial and cortical amygdala during anticipation for daily nursing in the rabbit.

Rabbits have remarkable nursing behavior: after parturition, does visit daily their pups for nursing only once with circadian periodicity. Before the nursing events, they present increased activity and arousal, which shift according to the timing of scheduled nursing, either during the day or night. Brain areas related to maternal behavior and neuroendocrine cells for milk secretion are also entrained. The daily return of the doe for nursing at approximately the same hour suggests a motivational drive with circadian periodicity. Previously, we reported the activation of the mesolimbic system at the time of nursing, but not 12 h before that. Aiming at a better understanding of the mechanism of this anticipatory behavior, we explored the participation of the limbic regions of the amygdala and the bed nucleus of the stria terminalis, as well as the possible activation of the hypothalamic-pituitaryadrenal axis, specifically the corticotropin-releasing factor cells in the hypothalamic paraventricular nucleus of does at different times before and after nursing. The medial and cortical amygdala, the bed nucleus of the stria terminalis, and corticotropin cells showed activation only after nursing. However, the central amygdala was also activated before nursing. We conclude that the medial and the cortical amygdala form part of the afferent olfactory pathway for entrainment, and the central amygdala participates in the anticipatory motivational circuit of the control of periodic nursing. The lack of activation of corticotropin cells before nursing is consistent with the possible harmful effects of the doe's high glucocorticoid levels on the developing pups.