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We previously reported that cerebral activation at the onset of voluntary locomotion suppressed baroreflex control of heart rate (HR) and increased arterial pressure via vasopressin V1a receptors in the brain. Here, we examined whether these responses were associated with food seeking, a motivated behavior, using free-moving wild type (WT, n = 10), V1a receptor knockout (KO, n = 9), and wild-type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n = 10). For three consecutive days, mice were fed ad libitum (Fed), food deprived (FD), and refed (RF) under a dark/light cycle (1900/0700). Food was removed on day 2 and restored on day 3 at 1800. Throughout the protocol, cerebral activity was determined from the power density ratio of θ- to δ-wave band θ/δ) by electroencephalogram every 4 s. Baroreflex was evaluated by the cross-correlation function [R(t)] between changes in HR and arterial pressure every 4 s. The cerebro-baroreflex linkage was then evaluated by the cross-correlation function between h/d and R(t). Behavior was recorded with CCD camera. We found that cerebro-barore- flex linkage, enhanced in WT at night after FD (P = 0.006), returned to Fed level after RF (P = 0.68). Similarly, food-seeking behavior increased after FD to a level twofold higher than during Fed (P < 0.001) and returned to Fed level after RF (P = 0.54). However, none of these changes occurred in KO or BLK (P > 0.11). Thus, the suppression of baroreflex control of HR linked with cerebral activation via central V1a receptors might play an important role at the onset of motivated behaviors, such as food seeking induced by FD. [ABSTRACT FROM AUTHOR]

The brain continuously receives diverse information about the external environment and changes in the homeostatic state. The attribution of salience determines which stimuli capture attention and, therefore, plays an essential role in regulating emotions and guiding behaviors. Although the thalamus is included in the salience network, the neural mechanism of how the thalamus contributes to salience processing remains elusive. In this mini-review, we will focus on recent advances in understanding the specific roles of distinct thalamic nuclei in salience processing. We will summarize the functional connections between thalamus nuclei and other key nodes in the salience network. We will highlight the convergence of neural circuits involved in reward and pain processing, arousal, and attention control in thalamic structures. We will discuss how thalamic activities represent salience information in associative learning and how thalamic neurons modulate adaptive behaviors. Lastly, we will review recent studies which investigate the contribution of thalamic dysfunction to aberrant salience processing in neuropsychiatric disorders, such as drug addiction, posttraumatic stress disorder (PTSD), and schizophrenia. Based on emerging evidence from both human and rodent research, we propose that the thalamus, different from previous studies that as an information relay, has a broader role in coordinating the cognitive process and regulating emotions.

Systemic infections of all types lead to a syndrome known as sickness behaviors. Changes in the behavior of febrile humans and animals formed the original basis for this concept. Body temperature is behaviorally regulated in both endotherms and ectotherms. However, infections cause other changes in body functions, including sleep disruption, anorexia, cognitive and memory deficits and disorientation. The brain mediates this entire cluster of symptoms, even though most major infections occur outside the brain. The true importance of sickness behaviors is not the numerous discoveries of symptoms that affect all of us when we get sick. Instead, the legacy of 30 years of research in sickness behaviors is that it established the physiologic importance of reciprocal communication systems between the immune system and the brain. This conceptual advance remains in its infancy.

The brain continuously receives diverse information about the external environment and changes in the homeostatic state. The attribution of salience determines which stimuli capture attention and, therefore, plays an essential role in regulating emotions and guiding behaviors. Although the thalamus is included in the salience network, the neural mechanism of how the thalamus contributes to salience processing remains elusive. In this mini-review, we will focus on recent advances in understanding the specific roles of distinct thalamic nuclei in salience processing. We will summarize the functional connections between thalamus nuclei and other key nodes in the salience network. We will highlight the convergence of neural circuits involved in reward and pain processing, arousal, and attention control in thalamic structures. We will discuss how thalamic activities represent salience information in associative learning and how thalamic neurons modulate adaptive behaviors. Lastly, we will review recent studies which investigate the contribution of thalamic dysfunction to aberrant salience processing in neuropsychiatric disorders, such as drug addiction, posttraumatic stress disorder (PTSD), and schizophrenia. Based on emerging evidence from both human and rodent research, we propose that the thalamus, different from previous studies that as an information relay, has a broader role in coordinating the cognitive process and regulating emotions. [ABSTRACT FROM AUTHOR]

• Mesocorticolimbic dopamine signaling underlies motivated behaviors. • Mesocorticolimbic dopamine is modulated by gonadal hormones. • Gonadal hormones may mediate some early life stress-induced changes in dopamine. • Gonadal hormones are a potential therapeutic target for motivation-related deficits. Motivated behaviors are controlled by the mesocorticolimbic dopamine (DA) system, consisting of projections from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) and prefrontal cortex (PFC), with input from structures including the medial preoptic area (mPOA). Sex differences are present in this circuit, and gonadal hormones (e.g., estradiol and testosterone) are important for regulating DA transmission. Early life stress (ELS) also regulates the mesocorticolimbic DA system. ELS modifies motivated behaviors and the underlying DA circuitry, increasing risk for disorders such as substance use disorder, major depression, and schizophrenia. ELS has been shown to change gonadal hormone signaling in both sexes. Thus, one way that ELS could impact mesocorticolimbic DA is by altering the efficacy of gonadal hormones. This review provides evidence for this idea by integrating the gonadal hormone, motivation, and ELS literature to argue that ELS alters gonadal hormone signaling to impact motivated behavior. We also discuss the importance of these effects in the context of understanding risk and treatments for psychiatric disorders in men and women. [ABSTRACT FROM AUTHOR]

Systemic infections of all types lead to a syndrome known as sickness behaviors. Changes in the behavior of febrile humans and animals formed the original basis for this concept. Body temperature is behaviorally regulated in both endotherms and ectotherms. However, infections cause other changes in body functions, including sleep disruption, anorexia, cognitive and memory deficits and disorientation. The brain mediates this entire cluster of symptoms, even though most major infections occur outside the brain. The true importance of sickness behaviors is not the numerous discoveries of symptoms that affect all of us when we get sick. Instead, the legacy of 30 years of research in sickness behaviors is that it established the physiologic importance of reciprocal communication systems between the immune system and the brain. This conceptual advance remains in its infancy. [ABSTRACT FROM AUTHOR]

GABAergic neurons in the laterodorsal tegmental nucleus (LDTGABA) encode aversion by directly inhibiting mesolimbic dopamine (DA). Yet, the detailed cellular and circuit mechanisms by which these cells relay unpleasant stimuli to DA neurons and regulate behavioral output remain largely unclear. Here, we show that LDTGABA neurons bidirectionally respond to rewarding and aversive stimuli in mice. Activation of LDTGABA neurons promotes aversion and reduces DA release in the lateral nucleus accumbens. Furthermore, we identified two molecularly distinct LDTGABA cell populations. Somatostatin-expressing (Sst+) LDTGABA neurons indirectly regulate the mesolimbic DA system by disinhibiting excitatory hypothalamic neurons. In contrast, Reelin-expressing LDTGABA neurons directly inhibit downstream DA neurons. The identification of separate GABAergic subpopulations in a single brainstem nucleus that relay unpleasant stimuli to the mesolimbic DA system through direct and indirect projections is critical for establishing a circuit-level understanding of how negative valence is encoded in the mammalian brain. [Display omitted] • LDTGABA neurons bidirectionally respond to rewarding and aversive stimuli in mice • Sst+ LDTGABA interneurons encode reward by indirect disinhibition of mesolimbic DA system • VTA-projecting LDTGABA neurons promote aversion by directly inhibiting VTA DA neurons • VTA-projecting LDTGABA neurons selectively express Reelin Du et al. reveal that two separate populations of LDTGABA neurons are involved in the regulation of distinct behavioral reactions to unpleasant stimuli. Long-range VTA-projecting (Reelin+) LDTGABA neurons directly relay aversive stimuli to the mesolimbic DA system. Sst-expressing LDTGABA interneurons conversely regulate the mesolimbic DA system through hypothalamic circuitry. [ABSTRACT FROM AUTHOR]

The consensus view of the ventromedial nucleus of the hypothalamus (VMH) is that it is a key node in the rodent brain network controlling sympathoadrenal counterregulatory responses to hypoglycemia. To identify the location of hypoglycemia-responsive neurons in the VMH, we performed a high spatial resolution Fos analysis in the VMH of rats made hypoglycemic with intraperitoneal injections of insulin. We examined Fos expression in the four constituent parts of VMH throughout its rostrocaudal extent and determined their relationship to blood glucose concentrations. Hypoglycemia significantly decreased Fos expression only in the dorsomedial and central parts of the VMH, but not its anterior or ventrolateral parts. Moreover, the number of Fos-expressing neurons was significantly and positively correlated in the two responsive regions with terminal blood glucose concentrations. We also measured Fos responses in the paraventricular nucleus of the hypothalamus (PVH) and in several levels of the periaqueductal gray (PAG), which receives strong projections from the VMH. We found the expected and highly significant increase in Fos in the neuroendocrine PVH, which was negatively correlated to terminal blood glucose concentrations, but no significant differences were seen in any part of the PAG. Our results show that there are distinct populations of VMH neurons whose Fos expression is suppressed by hypoglycemia, and their numbers correlate with blood glucose. These findings support a clear division of glycemic control functions within the different parts of the VMH. [ABSTRACT FROM AUTHOR]

Abstract: More than 20years ago, melanin-concentrating hormone (MCH) and its peptide family members – neuropeptide EI (NEI) and neuropeptide GE (NGE) – were described in various species, including mammals (rodents, humans, and non-human primates). Since then, most studies have focused on the role of MCH as an orexigenic peptide, as well as on its participation in learning, spatial memory, neuroendocrine control, and sleep. It has been shown that MCH mRNA or the neuropeptide MCH are present in neurons of the prosencephalon, hypothalamus and brainstem. However, most of the neurons containing MCH/NEI are within the incerto-hypothalamic and lateral hypothalamic areas. In addition, the terminals of those neurons are distributed widely throughout the central nervous system. In this review, we will discuss the relationship between those territories and the roles played by MCH/NEI, as well as the importance of MCH receptor 1 in the respective terminal fields. Certain neurochemical features of MCH- and NEI-immunoreactive (MCH-ir and NEI-ir) neurons will also be discussed. The overarching theme is the anatomical organization of an inhibitory neuropeptide colocalized with an inhibitory neurotransmitter in integrative territories of the central nervous system, such as the IHy and LHA. Although these territories have connections to few brain regions, the regions to which they are connected are relevant, being responsible for the organization of motivated behaviors. All available information on this peptidergic system (anatomical, neurochemical, hodological, physiological, pharmacological and behavioral data) suggests that MCH is intimately involved in arousal and the initiation of motivated behaviors. [Copyright &y& Elsevier]

It has been suggested that the cortico- and limbic-striatal systems are important in various motor functions such as motivated behaviors. In this paper we review our previous studies to investigate neuronal mechanisms of feeding behaviors. We recorded neuronal activity from the amygdala, caudate nucleus, globus pallidus, and substantia nigra during feeding behavior in monkeys, and compared neuronal responses recorded from these brain areas. First, of 710 amygdalar neurons tested, 129 (18.2%) responded to single sensory stimulation (48 to vision, 32 to audition, 49 to ingestion), 142 (20%) to multimodal stimulation, and 20 to only one item with affective significance. Eight food related amygdalar neurons were tested in reversal by salting food or introducing saline, and all responses were modulated by reversal. These results suggest that the amygdala might be important in ongoing recognition of the affective significance of complex stimuli (food-nonfood discrimination). Second, activity was recorded from 351 neurons in the head of the caudate nucleus of monkeys during an operant feeding task. The 16% of these neurons responded in the discrimination phase. Some of these neurons responded specifically to food. The magnitude of these food-specific neurons depend on the rewarding nature of the food (reward value), and was inversely related to the latency of the onset of bar press. Of the caudate neurons, 10% responded in the bar press phase. Activity of most neurons which responded in the bar press phase was not correlated to individual bar presses. Cooling of the dorsolateral prefrontal cortex abolished sustained responses during bar pressing, but did not abolish the feeding behavior. However, bar press speed tended to be delayed by prefrontal cooling. Third, activity of 358 neurons was recorded from the monkey globus pallidus, and 204 neurons responded during the feeding task. In the globus pallidus, few neurons responded to food in the discrimination phase. On the other hand, activity of most responsive neurons changed during bar press and/or ingestion phases. Activity of about half of these responsive neurons was directly related to specific feeding motor acts such as arm extension, flexion, bar pressing, grasping, chewing, etc. Some of these neurons showed motor-related responses with gradual and preparatory responses. These motor-related neurons were located mainly in the caudodorsal part of the globus pallidus. On the other hand, about one third, especially in the rostroventral part of the globus pallidus, showed dissociating responses in that they responded during bar pressing for food or during ingestion in an operant task, but not during bar pressing for nonfood or during forcible ingestion. The response magnitude of the neurons during arm extension and bar pressing depended on the nature of the food. Fourth, activity of 261 neurons was recorded from the substantia nigra pars reticulata. Most of responding neurons (more than two-thirds of the recorded neurons) responded during the bar press and/or ingestion phases. Activity of the one-third of neurons was related to specific motor execution such as arm extension, flexion and bar pressing, but not to motor preparation. These neurons were located mainly in the rostral part of the nucleus. More than one-third of the recorded neurons responded during feed and/or drinking acts and intra- and perioral sensory stimuli, and were located mainly in the caudomedial part of the nucleus. Based upon these responses and known anatomical evidence, various information including that from the amygdala and prefrontal cortex is integrated in the basal ganglia, and converted to coordinated motivated behaviors such as feeding behavior. [ABSTRACT FROM AUTHOR]

We previously reported that cerebral activation at the onset of voluntary locomotion suppressed baroreflex control of heart rate (HR) and increased arterial pressure via vasopressin V1a receptors in the brain. Here, we examined whether these responses were associated with food seeking, a motivated behavior, using free-moving wild type (WT, n = 10), V1a receptor knockout (KO, n = 9), and wild-type mice locally infused with a V1a receptor antagonist into the nucleus tractus solitarii (BLK, n = 10). For three consecutive days, mice were fed ad libitum (Fed), food deprived (FD), and refed (RF) under a dark/light cycle (1900/0700). Food was removed on day 2 and restored on day 3 at 1800. Throughout the protocol, cerebral activity was determined from the power density ratio of θ- to δ-wave band (θ/δ) by electroencephalogram every 4 s. Baroreflex was evaluated by the cross-correlation function [ R ( t )] between changes in HR and arterial pressure every 4 s. The cerebro-baroreflex linkage was then evaluated by the cross-correlation function between θ/δ and R ( t ). Behavior was recorded with CCD camera. We found that cerebro-baroreflex linkage, enhanced in WT at night after FD ( P = 0.006), returned to Fed level after RF ( P = 0.68). Similarly, food-seeking behavior increased after FD to a level twofold higher than during Fed ( P < 0.001) and returned to Fed level after RF ( P = 0.54). However, none of these changes occurred in KO or BLK ( P > 0.11). Thus, the suppression of baroreflex control of HR linked with cerebral activation via central V1a receptors might play an important role at the onset of motivated behaviors, such as food seeking induced by FD. NEW & NOTEWORTHY Motivated behaviors, characterized by goal-directed and persistent movements, are indispensable for living. However, how cerebro-cardiovascular adjustment occurs during such behaviors remains unknown. By focusing on food-seeking behavior in a food-deprived condition using free-moving mice, we found that this condition enhanced the linkage between cerebral activation and suppression of baroreflex control of heart rate through central vasopressin V1a receptors, making it easier to start motivated behaviors by enhancing pressor response.

Significant evidence supports the view that dopamine shapes learning by encoding reward prediction errors. However, it is unknown whether striatal targets receive tailored dopamine dynamics based on regional functional specialization. Here, we report wave-like spatiotemporal activity patterns in dopamine axons and release across the dorsal striatum. These waves switch between activational motifs and organize dopamine transients into localized clusters within functionally related striatal subregions. Notably, wave trajectories were tailored to task demands, propagating from dorsomedial to dorsolateral striatum when rewards are contingent on animal behavior and in the opponent direction when rewards are independent of behavioral responses. We propose a computational architecture in which striatal dopamine waves are sculpted by inference about agency and provide a mechanism to direct credit assignment to specialized striatal subregions. Supporting model predictions, dorsomedial dopamine activity during reward-pursuit signaled the extent of instrumental control and interacted with reward waves to predict future behavioral adjustments. [Display omitted] • Dorsal striatum receives wave-like dopamine dynamics • Motif flow patterns produce delayed DA transients across striatal subregions • Opponent DA wave directions predict behavioral control of reward • Computational model links multi-timescale DA signals: transients, ramps, and waves Dopamine axon activity and release across the dorsal striatum in mice exhibits wave-like spatiotemporal patterns that are tailored to task demands and predict an animal's behavioral adjustments. [ABSTRACT FROM AUTHOR]