The cognitive functions of the caudate nucleus

The basal ganglia as a whole are broadly responsible for sensorimotor coordination, including response selection and initiation. However, it has become increasingly clear that regions of the basal ganglia are functionally delineated along corticostriatal lines, and that a modular conception of the respective functions of various nuclei is useful. Here we examine the specific role of the caudate nucleus, and in particular, how this differs from that of the putamen. This review considers converging evidence from multiple domains including anatomical studies of corticostriatal circuitry, neuroimaging studies of healthy volunteers, patient studies of performance deficits on a variety of cognitive tests, and animal studies of behavioural control. We conclude that the caudate nucleus contributes to behaviour through the excitation of correct action schemas and the selection of appropriate sub-goals based on an evaluation of action-outcomes; both processes fundamental to successful goal-directed action. This is in contrast to the putamen, which appears to subserve cognitive functions more limited to stimulus-response, or habit, learning. This modular conception of the striatum is consistent with hierarchical models of cortico-striatal function through which adaptive behaviour towards significant goals can be identified (motivation; ventral striatum), planned (cognition; caudate) and implemented (sensorimotor coordination; putamen) effectively.     

The human sexual response cycle: brain imaging evidence linking sex to other pleasures

Sexual behavior is critical to species survival, yet comparatively little is known about the neural mechanisms in the human brain. Here we systematically review the existing human brain imaging literature on sexual behavior and show that the functional neuroanatomy of sexual behavior is comparable to that involved in processing other rewarding stimuli. Sexual behavior clearly follows the established principles and phases for wanting, liking and satiety involved in the pleasure cycle of other rewards. The studies have uncovered the brain networks involved in sexual wanting or motivation/anticipation, as well as sexual liking or arousal/consummation, while there is very little data on sexual satiety or post-orgasmic refractory period. Human sexual behavior also interacts with other pleasures, most notably social interaction and high arousal states. We discuss the changes in the underlying brain networks supporting sexual behavior in the context of the pleasure cycle, the changes to this cycle over the individual's life-time and the interactions between them. Overall, it is clear from the data that the functional neuroanatomy of sex is very similar to that of other pleasures and that it is unlikely that there is anything special about the brain mechanisms and networks underlying sex.     

Chronic non-invasive corticosterone administration abolishes the diurnal pattern of tph2 expression

Both hypothalamic-pituitary-adrenal (HPA) axis activity and serotonergic systems are commonly dysregulated in stress-related psychiatric disorders. We describe here a non-invasive rat model for hypercortisolism, as observed in major depression, and its effects on physiology, behavior, and the expression of tph2, the gene encoding tryptophan hydroxylase 2, the rate-limiting enzyme for brain serotonin (5-hydroxytryptamine; 5-HT) synthesis. We delivered corticosterone (40 μg/ml, 100 μg/ml or 400 μg/ml) or vehicle to adrenal-intact adult, male rats via the drinking water for 3 weeks. On days 15, 16, 17 and 18, respectively, the rats' emotionality was assessed in the open-field (OF), social interaction (SI), elevated plus-maze (EPM), and forced swim tests (FST). On day 21, half of the rats in each group were killed 2h into the dark phase of a 12/12 h reversed light/dark cycle; the other half were killed 2h into the light phase. We then measured indices of HPA axis activity, plasma glucose and interleukin-6 (IL-6) availability, and neuronal tph2 expression at each time point. Chronic corticosterone intake was sufficient to cause increased anxiety- and depressive-like behavior in a dose-dependent manner. It also disrupted the diurnal pattern of plasma adrenocorticotropin (ACTH), corticosterone, and glucose concentrations, caused adrenal atrophy, and prevented regular weight gain. No diurnal or treatment-dependent changes were found for plasma concentrations of IL-6. Remarkably, all doses of corticosterone treatment abolished the diurnal variation of tph2 mRNA expression in the brainstem dorsal raphe nucleus (DR) by elevating the gene's expression during the animals' inactive (light) phase. Our data demonstrate that chronic elevation of corticosterone creates a vulnerability to a depression-like syndrome that is associated with increased tph2 expression, similar to that observed in depressed patients.     

Evidence for involvement of the lateral parabrachial nucleus in mediation of cholinergic inputs to neurons in the rostral ventrolateral medulla of the rat

We examined whether sites in the lateral parabrachial nucleus (PBN) where

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-glutamate produced increases in arterial pressure were involved in mediation of cholinergic inputs to neurons in the rostral ventrolateral medulla (RVLM). Male Wistar rats were anesthetized, paralyzed and artificially ventilated. Unilateral microinjection of

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-glutamate into the lateral PBN produced a pressor response. Microinjection of the muscarinic receptor antagonist scopolamine into the unilateral RVLM inhibited the pressor response to

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-glutamate injected ipsilaterally into the lateral PBN, whereas microinjection of the cholinesterase inhibitor physostigmine into the RVLM enhanced it. PBN microinjection of

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-glutamate also enhanced the firing rate of RVLM sympathoexcitatory neurons and the enhancement of the firing rate was inhibited by scopolamine iontophoretically applied on neurons. PBN injection of

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-glutamate produced a tetrodotoxin (TTX)-sensitive release of ACh in the RVLM. Unilateral microinjection of TTX into the lateral PBN inhibited the pressor response induced by RVLM microinjection of physostigmine. These results provide evidence that neurons in the pressor sites of the lateral PBN are involved in mediation of cholinergic inputs responsible for pressor responses in the RVLM.     

Cardiovascular effects of agmatine within the rostral ventrolateral medulla are similar to those of clonidine in anesthetized rats

Agmatine was isolated from bovine brain in 1994. It exhibits various functions, as a consequence of which it meets the criteria for an endogenous brain neurotransmitter. However, its physiological action on the cardiovascular system remains unclear. This study was designed to clarify its cardiovascular effects when administered into the rostral ventrolateral medulla (RVLM) in anesthetized and paralyzed rats. Unilateral injection of clonidine (5 nmol) into the RVLM significantly decreased mean arterial pressure (MAP) and heart rate (HR). Unilateral injection of agmatine (5 nmol) produced similar effects to clonidine. The amplitude of the decrease in HR was the same as with clonidine, but the amplitude of the decrease in MAP was less pronounced. The cardiovascular inhibition induced by clonidine (5 nmol) and agmatine was abolished by idazoxan (5 nmol). Similar to clonidine, agmatine inhibited the pressor effect of l-glutamate (2 nmol) injected into the RVLM. The duration of this effect (about 6 min) was shorter than that observed with clonidine (about 12 min). Bilateral injection of agmatine into the RVLM inhibited the depressor response induced by baroreflex activation (electrical stimulation of the aortic nerve), and this effect was similar to, but less pronounced than, that induced by clonidine. Idazoxan (5 nmol) antagonized the cardiovascular effects of clonidine and agmatine within the RVLM. However, it produced a similar effect to clonidine injected into the RVLM. It is concluded that agmatine exerts a similar cardiovascular effect to clonidine, with less potency within the RVLM. Idazoxan might be a partial agonist for imidazoline I₁ receptors.     

Paraventricular neurosecretory neurons: synaptic inputs from the ventrolateral medulla in rats

Effects of electrical stimulation of the ventrolateral medulla on discharge activity of neurosecretory neurons in the paraventricular nucleus (PVN) were studied in male rats anesthetized with urethane-chloralose. Among 35 phasically firing neurosecretory neurons, stimulation of the lateral reticular nucleus and its vicinity produced excitation in 10 and inhibition in 2. The stimulation also enhanced the activity of 40% of the PVN neurosecretory neurons that fired continuously (n = 81); of these responsive neurons, half of the neurons tested (n = 12) were inhibited by i.v. administration of phenylephrine. The result suggests that both vasopressin- and oxytocin-secreting neurons in the PVN receive mainly excitatory synaptic inputs from the ventrolateral medulla.     

Glucose utilization,blood flow and capillary density in the ventrolateral medulla of the rat

A specific population of neurons in the ventrolateral medulla (VLM) acts as the main integration center for the regulation of the sympathetic outflow to the cardiovascular system. In order to investigate whether this nucleus can be distinguished from its surroundings in the reticular formation of the medulla with respect to functional and morphological variables, the present study investigates several of such variables in this area on a quantitative basis. Local medullary glucose utilization was measured by the 2-[¹⁴C]deoxyglucose method; local medullary blood flow was quantified using iodo[¹⁴C]-antipyrine, and the local density of perfused capillaries was calculated by counting the number of intravascular fluorescent spots in brain sections after i.v. infusion of a globulin-coupled fluorescent dye. The values obtained from the VLM were compared with the respective values found in a reference area of the same brain section (gigantocellular nucleus). The values for glucose utilization, blood flow and capillary density were significantly (P<0.05) higher in the VLM than in the reference area (gigantocellular nucleus). This difference was 44.7% for glucose utilization, 34.1% for blood flow and 19.7% for capillary density. These data support the hypothesis that neurons in the VLM are specifically well supplied for being directly regulated in their activity by the PCO₂ and pH in the arterial blood.     

Intrinsic gamma-aminobutyric acid neurons in the nucleus of the solitary tract and the rostral ventrolateral medulla of the rat: an immunocytochemical and biochemical study

Sympathoexcitatory neurons in the C1 adrenergic area of the rostral ventrolateral medulla (RVL) are tonically inhibited by gamma-aminobutyric acid (GABA). To identify the source of this GABAergic input, the distribution of neurons containing glutamate decarboxylase (GAD) was determined immunocytochemically in rats treated with colchicine. Numerous GAD-stained neurons were located in the nucleus of the solitary tract (NTS) and in RVL. Unilateral lesions in NTS did not alter GABA content or GAD activity in RVL, indicating that the afferent projection from NTS to RVL is not GABAergic. Intrinsic GABAergic neurons in RVL may provide tonic inhibition of vasomotor neurons in the C1 area.     

Enkephalin-like immunoreactivity within the telencephalon of the reptile Caiman crocodilus

Immunohistochemical methods were used to characterize the distribution of staining for leucine enkephalin-like and methionine enkephalin-like immunoreactivities in the telencephalon of Caiman crocodilus. Very similar distributions of both leucine enkephalin-like and methionine enkephalin-like immunoreactivity were observed. The greatest accumulations of enkephalin-like immunoreactive material were observed within the ventrolateral area of the telencephalon, a region considered comparable to the mammalian corpus striatum and avian paleostriatal complex (i.e. basal ganglia) on the basis of embryological, anatomical and histochemical criteria. Within the ventrolateral area, many small immunoreactive neuron cell bodies were observed, particularly within the rostromedial small-celled component of the ventrolateral telencephalic area. A rich plexus of fibers displaying enkephalin-like immunoreactivity invests the entire ventrolateral area including the large-celled subdivision. A system of thick, coarse, radially-directed immunoreactive fibers running between medial and dorsal portions of the ventrolateral area and more ventral portions was observed in this study. Other structures in the caiman telencephalon, containing large numbers of neural elements displaying enkephalin-like immunoreactivity, were the ventral paleostriatum (a region considered comparable to the ventral pallidum of mammals), the lateral septal nucleus and the nucleus accumbens. The corticoid areas contained far fewer elements displaying enkephalin-like immunoreactivity, although immunoreactive fibers and cell bodies were observed within the medial, dorsal and lateral corticoid areas, particularly at caudal levels. The dorsal ventricular ridge contains the lowest number of immunoreactive cells and fibers of any structure within the caiman telencephalon although occasional neurons displaying enkephalin-like immunoreactivity were encountered in the dorsal ventricular ridge. The results are compared to the distribution of enkephalin within the cerebral hemispheres of mammals, birds and other reptiles.     

A role for KATP-channels in mediating the elevations of cerebral blood flow and arterial pressure by hypoxic stimulation of oxygen-sensitive neurons of rostral ventrolateral medulla

Reticulospinal sympathoexcitatory neurons of rostral ventrolateral medulla (RVL) are selectively excited by hypoxia to elevate arterial pressure (AP) and cerebral blood flow (rCBF), that are elements of the oxygen-conserving (diving) reflex. We investigated whether K_ATP⁺-channels participate in this. Tolbutamide and glibenclamide, K_ATP⁺-channel blockers, microinjected into RVL in anesthetized rats, dose-dependently and site-specifically elevated AP and rCBF and potentiated responses to hypoxemia. K_ATP⁺-channels may mediate hypoxic excitation of oxygen-sensing RVL neurons.