A novel giant non-cholinergic striatal interneuron restricted to the ventrolateral striatum coexpresses Kv3.3 potassium channel, parvalbumin, and the vesicular GABA transporter.

The striatum is the main input structure of the basal ganglia. Distinct striatal subfields are involved in voluntary movement generation and cognitive and emotional tasks, but little is known about the morphological and molecular differences of striatal subregions. The ventrolateral subfield of the striatum (VLS) is the orofacial projection field of the sensorimotor cortex and is involved in the development of orofacial dyskinesias, involuntary chewing-like movements that often accompany long-term neuroleptic treatment.

The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area.

The lateral preoptic area (LPO) is a hypothalamic region whose function has been largely unexplored. Its direct and indirect projections to the ventral tegmental area (VTA) suggest that the LPO could modulate the activity of the VTA and the reward-related behaviors that the VTA underlies. We examined the role of the LPO on reward taking and seeking using operant self-administration of cocaine or sucrose.

Dissociable effects of dopamine D1 and D2 receptors on compulsive ingestion and pivoting movements elicited by disinhibiting the ventral pallidum.

Previous studies have shown that infusion of a GABA receptor antagonist, such as bicuculline (bic), into the ventral (pallidum VP) of rats elicits vigorous ingestion in sated subjects and abnormal pivoting movements. Here, we assessed if the ingestive effects generalize to the lateral preoptic area (LPO) and tested both effects for modulation by dopamine receptor signaling. Groups of rats received injections of the dopamine D2 receptor antagonist, haloperidol (hal), the D1 antagonist, SCH-23390 (SCH), or vehicle (veh) followed by infusions of bic or veh into the VP or LPO.

The lateral preoptic area and ventral pallidum embolden behavior.

While recently completing a study of the effects of stimulating the lateral preoptic area (LPO) and ventral pallidum (VP) on locomotion and other movements, we also noticed LPO and VP effects on motivational drive and threat tolerance. Here, we have investigated these latter effects by testing conditioned place preference (CPP), behavior on the elevated plus maze (EPM) and the willingness of sated rats to occupy a harshly lit open field center to acquire sweet pellets, a measure of threat tolerance, following infusions of vehicle or bicuculline (bic) into the LPO and VP. LPO-bic infusions robustly increased total locomotion, and, in direct proportion, occupancy of both the harshly lit field center and open arms of the EPM.

Lateral preoptic and ventral pallidal roles in locomotion and other movements.

The lateral preoptic area (LPO) and ventral pallidum (VP) are structurally and functionally distinct territories in the subcommissural basal forebrain. It was recently shown that unilateral infusion of the GABA receptor antagonist, bicuculline, into the LPO strongly invigorates exploratory locomotion, whereas bicuculline infused unilaterally into the VP has a negligible locomotor effect, but when infused bilaterally, produces vigorous, abnormal pivoting and gnawing movements and compulsive ingestion. This study was done to further characterize these responses.

Review of the cytology and connections of the lateral habenula, an avatar of adaptive behaving.

The cytology and connections of the lateral habenula (LHb) are reviewed. The habenula is first introduced, after which the cytology of the LHb is discussed mainly with reference to cell types, general topography and descriptions of subnuclei. An overview of LHb afferent connections is given followed by some details about the projections to LHb from a number of structures.

Abundant collateralization of temporal lobe projections to the accumbens, bed nucleus of stria terminalis, central amygdala and lateral septum.

Behavioral flexibility is subserved in part by outputs from the cerebral cortex to telencephalic subcortical structures. In our earlier evaluation of the organization of the cortical-subcortical output system (Reynolds and Zahm, J Neurosci 25:11757-11767, 2005), retrograde double-labeling was evaluated in the prefrontal cortex following tracer injections into pairs of the following subcortical telencephalic structures: caudate-putamen, core and shell of the accumbens (Acb), bed nucleus of stria terminalis (BST) and central nucleus of the amygdala (CeA). The present study was done to assess patterns of retrograde labeling in the temporal lobe after similar paired tracer injections into most of the same telencephalic structures plus the lateral septum (LS).

Sources of input to the rostromedial tegmental nucleus, ventral tegmental area, and lateral habenula compared: A study in rat.

Profound inhibitory control exerted on midbrain dopaminergic neurons by the lateral habenula (LHb), which has mainly excitatory outputs, is mediated by the GABAergic rostromedial tegmental nucleus (RMTg), which strongly innervates dopaminergic neurons in the ventral midbrain. Early reports indicated that the afferent connections of the RMTg, excepting its very strong LHb inputs, do not differ appreciably from those of the ventral tegmental area (VTA). Presumably, however, the RMTg contributes more to behavioral synthesis than to simply invert the valence of the excitatory signal coming from the LHb.

Modulation of locomotor activation by the rostromedial tegmental nucleus.

The rostromedial tegmental nucleus (RMTg) is a strong inhibitor of dopamine neurons in the ventral tegmental area (VTA) reported to influence neurobiological and behavioral responses to reward omission, aversive and fear-eliciting stimuli, and certain drugs of abuse. Insofar as previous studies implicate ventral mesencephalic dopamine neurons as an essential component of locomotor activation, we hypothesized that the RMTg also should modulate locomotion activation. We observed that bilateral infusions into the RMTg of the gamma-aminobutyric acid A (GABAA) agonist, muscimol, indeed activate locomotion.

Protracted maturation of forebrain afferent connections of the ventral tegmental area in the rat.

The mesocorticolimbic dopamine system has long attracted the interest of researchers concerned with the unique gamut of behavioral and mental health vulnerabilities associated with adolescence. Accordingly, the development of the mesocorticolimbic system has been studied extensively, but almost exclusively with regard to dopaminergic output, particularly in the nucleus accumbens and medial prefrontal cortex. To the contrary, the ontogeny of inputs to the ventral tegmental area (VTA), the source of mesocorticolimbic dopamine, has been neglected.

Oxytocin projections to the nucleus of the solitary tract contribute to the increased meal-related satiety responses in primary adrenal insufficiency.

Anorexia is a common clinical manifestation of primary adrenal gland failure. Adrenalectomy (ADX)-induced hypophagia is reversed by oxytocin (OT) receptor antagonist and is associated with increased activation of satiety-related responses in the nucleus of the solitary tract (NTS). This study evaluated OT projections from the paraventricular nucleus of the hypothalamus (PVN) to the NTS after ADX and the effect of pretreatment with intracerebroventricular injection of an OT receptor antagonist ([d(CH2)5,Tyr(Me)(2),Orn(8)]-vasotocin; OVT) on the activation of NTS neurons induced by feeding in adrenalectomized rats.

Comparison of the locomotor-activating effects of bicuculline infusions into the preoptic area and ventral pallidum.

Ambulatory locomotion in the rodent is robustly activated by unilateral infusions into the basal forebrain of type A gamma-aminobutyric acid receptor antagonists, such as bicuculline and picrotoxin. The present study was carried out to better localize the neuroanatomical substrate(s) underlying this effect. To accomplish this, differences in total locomotion accumulated during a 20-min test period following bicuculline versus saline infusions in male Sprague-Dawley rats were calculated, rank ordered and mapped on a diagram of basal forebrain transposed from immunoprocessed sections.

On lateral septum-like characteristics of outputs from the accumbal hedonic "hotspot" of Peciña and Berridge with commentary on the transitional nature of basal forebrain "boundaries".

Peciña and Berridge (2005; J Neurosci 25:11777-11786) observed that an injection of the μ-opioid receptor agonist DAMGO (D-ala(2) -N-Me-Phe(4) -Glycol(5) -enkephalin) into the rostrodorsal part of the accumbens shell (rdAcbSh) enhances expression of hedonic "liking" responses to the taste of an appetitive sucrose solution. Insofar as the connections of this hedonic "hotspot" were not singled out for special attention in the earlier neuroanatomical literature, we undertook to examine them. We observed that the patterns of inputs and outputs of the rdAcbSh are not qualitatively different from those of the rest of the Acb, except that outputs from the rdAcbSh to the lateral preoptic area and anterior and lateral hypothalamic areas are anomalously robust and overlap extensively with those of the lateral septum.

Separate prefrontal-subcortical circuits mediate different components of risk-based decision making.

Choosing between smaller, assured rewards or larger, uncertain ones requires reconciliation of competing biases toward more certain or riskier options. We used disconnection and neuroanatomical techniques to reveal that separate, yet interconnected, neural pathways linking the medial prefrontal cortex (PFC), the basolateral amygdala (BLA), and nucleus accumbens (NAc) contribute to these different decision biases in rats. Disrupting communication between the BLA and NAc revealed that this subcortical circuit biases choice toward larger, uncertain rewards on a probabilistic discounting task.

Mesopontine rostromedial tegmental nucleus neurons projecting to the dorsal raphe and pedunculopontine tegmental nucleus: psychostimulant-elicited Fos expression and collateralization.

The mesopontine rostromedial tegmental nucleus (RMTg) is a GABAergic structure in the ventral midbrain and rostral pons that, when activated, inhibits dopaminergic neurons in the ventral tegmental area and substantia nigra compacta. Additional strong outputs from the RMTg to the pedunculopontine tegmental nucleus pars dissipata, dorsal raphe nucleus, and the pontomedullary gigantocellular reticular formation were identified by anterograde tracing. RMTg neurons projecting to the ventral tegmental area express the immediate early gene Fos upon psychostimulant administration.

The mesopontine rostromedial tegmental nucleus: an integrative modulator of the reward system.

The mesopontine rostromedial tegmental nucleus (RMTg) is a newly discovered brain structure thought to profoundly influence reward-related pathways. The RMTg is prominently GABAergic, receives dense projections from the lateral habenula and projects strongly to the midbrain ventral tegmental area and substantia nigra compacta. It receives additional afferent connections from widespread brain structures and sends additional strong efferent connections to a number of non-dopaminergic brainstem structures and, to a lesser extent, the forebrain.

Inputs to the midbrain dopaminergic complex in the rat, with emphasis on extended amygdala-recipient sectors.

The midbrain dopaminergic neuronal groups A8, A9, A10, and A10dc occupy, respectively, the retrorubral field (RRF), substantia nigra compacta (SNc), ventral tegmental area (VTA), and ventrolateral periaqueductal gray (PAGvl). Collectively, these structures give rise to a mixed dopaminergic and nondopaminergic projection system that essentially permits adaptive behavior. However, knowledge is incomplete regarding how the afferents of these structures are organized.

Pharmacotherapeutic approach to the treatment of addiction: persistent challenges.

The sequence of pathophysiological responses to repeated self-administration of addictive compounds is briefly described, as are prospects for development of drugs for addiction and some of those currently available. It is noted that the varying vulnerability of individuals to addictions creates ethical concerns regarding the application of drug abuse pharmacotherapies as they become more efficacious. It is noted further that relapse remains the most persistent challenge in the treatment of addictions.

Fos after single and repeated self-administration of cocaine and saline in the rat: emphasis on the Basal forebrain and recalibration of expression.

The effects of addictive psychostimulant drugs on the brain change over repeated administrations. We evaluated a large sample of brain structures, particularly ones comprising basal forebrain macrosystems, and determined in which the immediate-early gene product, Fos, is expressed following a single and repeated self-administrations of cocaine. The caudate-putamen and accumbens, comprising the basal ganglia input structures, and the hypothalamic supraoptic and paraventricular nuclei, lateral and medial habenula, mesopontine rostromedial tegmental nucleus and anterior cingulate cortex exhibited Fos expression enhanced by acute self-administration of cocaine (SAC), but desensitized after repeated administrations.

Altered dendritic spine plasticity in cocaine-withdrawn rats.

Chronic cocaine treatment is associated with changes in dendritic spines in the nucleus accumbens, but it is unknown whether this neuroplasticity alters the effect of a subsequent cocaine injection on spine morphology and protein content. Three weeks after daily cocaine or saline administration, neurons in the accumbens were filled with the lipophilic dye, DiI. Although daily cocaine pretreatment did not alter spine density compared with daily saline, there was a shift from smaller to larger diameter spines.

The mesopontine rostromedial tegmental nucleus: A structure targeted by the lateral habenula that projects to the ventral tegmental area of Tsai and substantia nigra compacta.

Prior studies revealed that aversive stimuli and psychostimulant drugs elicit Fos expression in neurons clustered above and behind the interpeduncular nucleus that project strongly to the ventral tegmental area (VTA) and substantia nigra (SN) compacta (C). Other reports suggest that these neurons modulate responses to aversive stimuli. We now designate the region containing them as the "mesopontine rostromedial tegmental nucleus" (RMTg) and report herein on its neuroanatomy.

The dopaminergic projection system, basal forebrain macrosystems, and conditioned stimuli.

This review begins with a description of some problems that recently have beset an influential circuit model of fear conditioning and goes on to look at neuroanatomy that may subserve conditioning viewed in a broader perspective, including not only fear but also appetitive conditioning. The column will then focus on basal forebrain functional-anatomical systems, or macrosystems, as they have come to be called. Yet, more specific attention is then given to the relationships of the dorsal and ventral striatopallidal systems and extended amygdala with the dopaminergic mesotelencephalic projection systems, culminating with the hypothesis that all macrosystems contribute to behavioral conditioning.

Prominent activation of brainstem and pallidal afferents of the ventral tegmental area by cocaine.

Blockade of monoamine transporters by cocaine should not necessarily lead to certain observed consequences of cocaine administration, including increased firing of ventral mesencephalic dopamine (DA) neurons and accompanying impulse-stimulated release of DA in the forebrain and cortex. Accordingly, we hypothesize that the dopaminergic-activating effect of cocaine requires stimulation of the dopaminergic neurons by afferents of the ventral tegmental area (VTA). We sought to determine if afferents of the VTA are activated following cocaine administration.

Activation of afferents to the ventral tegmental area in response to acute amphetamine: a double-labelling study.

The ventral tegmental area (VTA), primary source of the mesocorticolimbic dopaminergic system, is regarded as a critical site for initiation of behavioural sensitization to psychostimulants. The present study was undertaken to identify the neural pathways converging on the VTA that are potentially implicated in this process. Rats were sensitized by a single exposure to amphetamine (5 mg/kg, s.

Glutamatergic afferents of the ventral tegmental area in the rat.

Glutamatergic inputs to the ventral tegmental area (VTA), thought crucial to the capacity of the VTA to detect and signal stimulus salience, have been reported to arise in but a few structures. However, the afferent system of the VTA comprises very abundant neurons within a large formation extending from the prefrontal cortex to the caudal brainstem. Neurons in nearly all parts of this continuum may be glutamatergic and equivalently important to VTA function.