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PubMed2005

Compartmental modeling of transdermal iontophoretic transport II: in vivo model derivation and application.

PURPOSE: This study was aimed to develop a family of compartmental models to describe in a strictly quantitative manner the transdermal iontophoretic transport of drugs in vivo. The new models are based on previously proposed compartmental models for the transport in vitro. METHODS: The novel in vivo model considers two separate models to describe the input into the systemic circulation: a) constant input and b) time-variant input. Analogous to the in vitro models, the in vivo models contain four parameters: 1) kinetic lag time (tL), 2) steady-state flux during iontophoresis (JSS), 3) skin release rate constant (KR), and 4) passive flux in the post-iontophoretic period (Jpas). The elimination from the systemic circulation is described by a) the one-compartment and b) the two-compartment pharmacokinetic models. The models were applied to characterize the observed plasma concentration vs. time data following single-dose iontophoretic delivery of growth hormone-releasing factor (GRF) and R-apomorphine. Moreover, the models were also used to simulate the observed plasma concentration vs. time profiles following a two-dose transdermal iontophoretic administration of alniditan. RESULTS: The time-variant input models were superior to the constant input models and appropriately converged to the observed data of GRF and R-apomorphine allowing the estimation of JSS, KR, and Jpas. In most cases, the values of tL were negligible. The estimated JSS and the in vivo flux profiles of GRF and R-apomorphine were similar to those obtained using the deconvolution method. The two-dose iontophoretic transport of alniditan was properly simulated using the proposed time-variant input model indicating the utility of the model to predict and to simulate the drug transport by a multiple-dose iontophoresis. Moreover, the use of the compartmental modeling approach to derive an in vitro-in vivo correlation for R-apomorphine was demonstrated. This approach was also used to identify the optimum in vitro model that closely mimics the in vivo iontophoretic transport of R-apomorphine. CONCLUSIONS: The developed in vivo models demonstrate their consistency and capability to describe the in vivo iontophoretic drug transport. This compartmental modeling approach provides a scientific basis to examine in vitro-in vivo correlations of drug transport by iontophoresis.

Administration, Cutaneous↗

PubMed1992

Functional compartmentalization of energy production in neural tissue.

Previous work in our laboratory has shown that neural trauma results in a disparity between oxidative and glycolytic rates. In non-neural tissue, glycolysis and oxidative phosphorylation have been shown to work independently of one another, a phenomenon known as "energy compartmentalization". We believe that functional compartmentalization of energy production may also occur in the brain with glycolysis providing energy for membrane bound ionic pumps. Spreading depression, induced in rodent brain by topical KCl application, results in K+ shifts. The restoration of K+ gradients is accomplished by energy dependent Na(+)-K+ pumps. If these pumps depend upon glycolysis, blocking glycolysis should prevent reconstitution of normal [K+]e levels. The present series of experiments were designed to suggest that energy compartmentalization may also exist in brain, and that glycolytic energy production is preferentially used by Na(+)-K+ pumps to maintain normal ionic homeostasis by observing the dynamics of spreading depression induced K+ shifts before and after glycolytic blockade. Spreading depression was associated with increased K+ (48.6 +/- 16.6 mM over control) that normalized within 2.9 +/- 0.3 minutes. Following superfusion with a glycolytic blocking agent, spreading depression produced similar increases in [K+]e (40.6 +/- 12.0 mM over control) but time for reconstitution of the normal [K+]e was 400% longer than controls (2.9 +/- 0.3 to 14.9 +/- 2.1 minutes, P less than 0.001). Time required for recovery of EEG was identical pre- and post-blockade. We believe these data suggest that energy compartmentalization may exist in neural tissue and that glycolytic pathways of energy production are functionally tied to membrane Na(+)-K+ pumps.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

The effect of tourniquet release on intra-compartmental pressure in the bandaged and unbandaged limb.

Changes in intra-compartmental pressure in bandaged and unbandaged limbs following 90 minutes of tourniquet-induced ischaemia and subsequent tourniquet release are examined in a primate model. Bandaging raises intra-compartmental pressure. Release of the tourniquet is shown to cause a transient increase in intra-compartmental pressure of less than 30 minutes duration. This is followed by a fall in intra-compartmental pressure for up to three hours. Tourniquet release and the ensuing hyperaemia does not appear to put the limb at risk of developing a compartment syndrome.

Animals↗

PubMed2026

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n = 48), meningitis (TI-; n = 80), (cranial) nerve palsies/polyradiculitis (PND; n = 61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p < 0.001/sGFAP p = 0.0083; CSF-NfL p = 0.003/sNfL p = 0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p = 0.0049/sGFAP p = 0.003). The overall group effect (p ≤ 0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p = 0.012/sNfL p = 0.002; CSF-GFAP p < 0.0001/CSF-NfL p = 0.0001), which also predicted unfavorable outcome at discharge (sGFAP p = 0.006/sNfL p = 0.004; CSF-GFAP p = 0.003/CSF-NfL p = 0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans↗

PubMedDate not supplied

Intracellular metabolic compartmentation assessed by 13C magnetic resonance spectroscopy.

Our understanding of the brain has developed from the theory that it is one continuous cell to the knowledge that there are many brain cells originally termed neurons and, furthermore to the discovery of glial cells and their multiple functions. Thus, an increasing complexity was unraveled and we have not reached a complete understanding of the phenomenon which comprises the compartmentation of metabolic pathways and metabolites. This is an important principle needed to fully understand the metabolic processes of the brain. At the cellular level this concept is well established whereas intracellular compartmentation has yet to be explored. Using magnetic resonance spectroscopy (MRS) for analysis of isotopomer composition combined with quantification of amino acid contents it is possible to construct models that describe intracellular compartmentation. Results of studies of cultures of astrocytes and neurons incubated in media containing [U- 13C]glutamate in the presence or absence of thiopental may be used to propose an intracellular three compartment model of mitochondrial function. Due to the experimental paradigm only certain aspects of metabolism can be described. The present model consists of compartments assigned to CO(2) production, glutamate synthesis from ketoglutarate and finally synthesis of a four-carbon metabolite which is shuttled between compartments. It is likely that metabolism may be far more complex than this and we are only beginning to glimpse some aspects of compartmentation at the cellular level.

Animals↗

PubMed1998

Raised compartmental pressure in children: a basis for management.

In children, raised intracompartmental pressure which may lead to a compartment syndrome is relatively common and follows a wide variety of insults. Cell viability is compromised at much lower compartmental pressures than in adults, and clinical awareness must be heightened, especially in the hypotensive child. Suspicion follows an awareness of clinical situations associated with the risk of raised compartmental pressure. Clinical confirmation may be difficult in the context of the uncooperative child. Diagnosis is established by invasive pressure monitoring. Intervention becomes mandatory when the compartmental pressure has risen to within 30 mmHg of the mean arterial pressure, which varies with the age and clinical status of the child. Management is by fasciotomy which should be wide and open and decompress all affected compartments. Thirty children with raised intracompartmental pressure are reported: 21 children were managed non-operatively and nine underwent fasciotomy. Two children with absolute intracompartmental pressures of 28 mmHg and 35 mmHg required fasciotomy, whereas five children with intra-compartmental pressures between 30 mmHg and 44 mmHg were managed non-operatively. In this latter group this policy resulted in no demonstrable morbidity.

Child↗

PubMed1998

Compartmentalization of calcium extrusion mechanisms in the outer and inner segments of photoreceptors.

Differential localization of calcium channel subtypes in divergent regions of individual neurons strongly suggests that calcium signaling and regulation could be compartmentalized. Region-specific expression of calcium extrusion transporters would serve also to partition calcium regulation within single cells. Little is known about selective localization of the calcium extrusion transporters, nor has compartmentalized calcium regulation within single neurons been studied in detail. Sensory neurons provide an experimentally tractable preparation to investigate this functional compartmentalization. We studied calcium regulation in the outer segment (OS) and inner segment/synaptic terminal (IS/ST) regions of rods and cones. We report these areas can function as separate compartments. Moreover, ionic, pharmacological, and immunolocalization results show that a Ca-ATPase, but not the Na+/K+, Ca2+ exchanger found in the OSs, extrudes calcium from the IS/ST region. The compartmentalization of calcium regulation in the photoreceptor outer and inner segments implies that transduction and synaptic signaling can be independently controlled. Similar separation of calcium-dependent functions is likely to apply in many types of neuron.

Animals↗

PubMed2006

Compartmentalization and evolution of feline immunodeficiency virus between the central nervous system and periphery following intracerebroventricular or systemic inoculation.

The emergence of distinct neuropathogenic strains resulting from the adaptation and the unique evolution of human immunodeficiency virus (HIV) in the brain may contribute to the development of HIV-induced neurological diseases. In this study, the authors tracked early changes in virus evolution and compartmentalization between peripheral tissues and the central nervous system (CNS) after intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) inoculation of animals with cell-free feline immunodeficiency virus (FIV). Using the FIV-NCSU1 envelope V3-V4 heteroduplex tracking assay (HTA), the authors observed a rapid compartmentalization of envelope variants between the CNS and periphery. Animals receiving the i.c.v. inoculation showed two peaks of viral RNA in the cerebrospinal fluid (CSF) with very different HTA patterns. Compared to the initial viral peak in CSF, the second peak showed an increased compartmentalization from plasma, reduced viral diversity, and more divergence from the proviral DNA in peripheral blood mononuclear cells (PBMCs) and the choroid plexus. In contrast, changes in plasma over the same time period were small. Different animals harbored different FIV DNA genotypes with varied regional compartmentalization within the brain. These results demonstrated that the virus within the CNS experienced a relatively independent but variable evolution from the periphery. Initial penetration of virus into the CSF facilitated the development of brain-specific reservoirs and viral diversification within the CNS.

Animals↗

PubMed2000

Subcellular compartmentalization of E2F family members is required for maintenance of the postmitotic state in terminally differentiated muscle.

Maintenance of cells in a quiescent state after terminal differentiation occurs through a number of mechanisms that regulate the activity of the E2F family of transcription factors. We report here that changes in the subcellular compartmentalization of the E2F family proteins are required to prevent nuclei in terminally differentiated skeletal muscle from reentering S phase. In terminally differentiated L6 myotubes, E2F-1, E2F-3, and E2F-5 were primarily cytoplasmic, E2F-2 was nuclear, whereas E2F-4 became partitioned between both compartments. In these same cells, pRB family members, pRB, p107, and p130 were also nuclear. This compartmentalization of the E2F-1 and E2F-4 in differentiated muscle cells grown in vitro reflected their observed subcellular location in situ. We determined further that exogenous E2F-1 or E2F-4 expressed in myotubes at levels fourfold greater than endogenous proteins compartmentalized identically to their endogenous counterparts. Only when overexpressed at higher levels was inappropriate subcellular location for these proteins observed. At these levels, induction of the E2F-regulated genes, cyclins A and E, and suppression of factors associated with myogenesis, myogenin, and p21(Cip1) was observed. Only at these levels of E2F expression did nuclei in these terminally differentiated cells enter S phase. These data demonstrate that regulation of the subcellular compartmentalization of E2F-family members is required to maintain nuclei in a quiescent state in terminally differentiated cells.

Animals↗

PubMed1998

A new method to estimate parameters of linear compartmental models using artificial neural networks.

At present, the preferred tool for parameter estimation in compartmental analysis is an iterative procedure; weighted nonlinear regression. For a large number of applications, observed data can be fitted to sums of exponentials whose parameters are directly related to the rate constants/coefficients of the compartmental models. Since weighted nonlinear regression often has to be repeated for many different data sets, the process of fitting data from compartmental systems can be very time consuming. Furthermore the minimization routine often converges to a local (as opposed to global) minimum. In this paper, we examine the possibility of using artificial neural networks instead of weighted nonlinear regression in order to estimate model parameters. We train simple feed-forward neural networks to produce as outputs the parameter values of a given model when kinetic data are fed to the networks' input layer. The artificial neural networks produce unbiased estimates and are orders of magnitude faster than regression algorithms. At noise levels typical of many real applications, the neural networks are found to produce lower variance estimates than weighted nonlinear regression in the estimation of parameters from mono- and biexponential models. These results are primarily due to the inability of weighted nonlinear regression to converge. These results establish that artificial neural networks are powerful tools for estimating parameters for simple compartmental models.

Algorithms↗

PubMed1983

Effect of acute compartmental pressure change on response to vibratory stimuli in primates.

This study investigated the possibility that a vibratory stimulus could discriminate the effect of relatively low pressures on nerve function in an acute compartmental syndrome in a primate model. The first phase of the study utilized somatosensory-evoked potentials to determine the outcome of varying pressures in an acute carpal tunnel syndrome in the anesthetized monkey. For increasing carpal tunnel pressures above 30 mmHg, the amplitude of the compound action potential of the A beta wave (touch fiber) generated in the median nerve by an electric stimulus to the index finger progressively decreased to a complete conduction block. It took progressively less time to achieve the conduction block at higher compartmental pressures. When compartmental pressure was released, the time required for the conduction block to return to normal was in direct relationship to the time required to complete the block. For carpal tunnel pressure between 15 and 30 mmHg, an increase in the height of this compound action potential was observed. The second phase of the study utilized the perceptual judgments of an awake monkey trained to discriminate differences in amplitude of a 10-Hz vibratory stimulus to the hairs of the dorsum of the foot. An anterior compartment pressure of 37 mmHg for 1 1/2 hours significantly decreased the monkey's ability to discriminate between the two amplitudes. At 50 mmHg in the anterior compartment, ability to discriminate between vibratory stimuli was further impaired. This study supports the use of noninvasive vibratory stimuli, such as a tuning fork, to evaluate acute compartmental syndromes.

Animals↗

PubMed1981

Compartmental syndromes in children.

Compartmental syndromes are reported in 24 children after injuries and surgery. In these cases, increased tissue pressure compromised local perfusion and neuromuscular function. Compartmental syndromes occurred in the interosseous compartments of the hand, the volar and dorsal compartments of the forearm, and the four compartments of the leg. The most common etiologies were fracture, vascular injury, and tibial osteotomy. In many instances, clinical data were sufficient to establish the diagnosis. However, in young patients or in patients with neurologic or vascular injuries, tissue pressure measurement helped to resolve otherwise ambiguous findings. The most significant determinant of the quality of the end result was the duration of the compartmental syndrome prior to surgical decompression. We conclude that prompt diagnosis and decompression of compartmental syndromes can minimize the sequela from these conditions.

Adolescent↗

PubMed2004

On nonoscillation and monotonicity of solutions of nonnegative and compartmental dynamical systems.

Nonnegative and compartmental dynamical system models are widespread in biological, physiological, and ecological sciences and play a key role in understanding these processes. In the specific field of pharmacokinetics involving the study of drug concentrations (in various tissue groups) as a function of time and dose, nonnegative and compartmental models are vital in understanding system wide effects of pharmacological agents. Since drug concentrations are often assumed to monotonically decline after discontinuation of drug administration, standard pharmacokinetic modeling may ignore the possibility of system oscillation. However, nonnegative and compartmental system models may exhibit nonmonotonic solutions resulting in differences between model predictions and experimental data. In this paper, we present necessary and sufficient conditions for identifying nonnegative and compartmental systems that only admit nonoscillatory and monotonic solutions.

Algorithms↗

PubMed1995

Nerve-dependent plasticity of the Golgi complex in skeletal muscle fibres: compartmentalization within the subneural sarcoplasm.

Several recent reports have highlighted the plasticity of the Golgi apparatus during myogenesis, yet the organization of this specialized organelle in innervated skeletal muscle fibres remains poorly understood. Using four bona fide anti-Golgi antibodies, directed against a 210 kDa protein, a 160 kDa sialoglycoprotein, the small GTP-binding protein rab6p, and TGN38, the localization of which covers the various compartments of the Golgi complex, we show by immunofluorescence microscopy that the Golgi complex undergoes considerable reorganization in the course of myogenic differentiation and motor endplate formation in the rat. Unlike the typical perinuclear distribution of the Golgi stacks associated with every nucleus in myotubes, a striking subneural compartmentalization is observed in adult innervated myofibres. In short-term denervated adult muscle fibres, we noticed the presence of the perinuclear Golgi apparatus in extrajunctional regions, a pattern reminiscent of that of developing myotubes. At variance with anti-Golgi antibodies, antibodies to the rough endoplasmic reticulum label structures dispersed throughout the entire sarcoplasm, hence suggesting that it is not the entire membrane/secretory protein synthesis machinery which is compartmentalized, but only the Golgi apparatus. Also, an unexpected lack of immunoreactivity with the TGN38 and alpha-mannosidase II antibodies points to biochemical differentiation of the subneural Golgi apparatus at the adult motor endplate. These new data extend our previous observations on the compartmentalization of the Golgi apparatus in the postsynaptic sarcoplasm of chick muscle fibres, and further illustrate the plasticity of the Golgi apparatus in muscle cells. The specialization of the Golgi apparatus within the subneural compartment provides this particular region with a compartmentalized secretory pathway, and these observations highlight the notion that the level of differentiation of this domain is not only maintained via transcriptional regulation but also by post-translational control mechanisms.

Animals↗

PubMed1988

The organization and development of compartmentalized innervation in rat extensor digitorum longus muscle.

1. We have examined the innervation of the rat extensor digitorum longus (EDL) muscle by the two extramuscular branches formed from the bifurcation of its muscle nerve. Observations of muscle contractions, recordings of end-plate potentials, and glycogen depletion of young adult muscles show that each branch innervates a separate region or 'compartment' in the muscle. The branch entering the muscle nearer the knee (the K branch) innervates fibres in the anteromedial half of the muscle whereas the branch entering closer to the foot (the F branch) innervates fibres located posterolaterally. Individual EDL motoneurones project either into the K or the F branch and therefore innervate fibres located in one compartment. The boundary between the compartments is usually sharply delineated. No obvious anatomical feature exists within the muscle which would explain the division of the muscle into two distinct regions. 2. The presence of a segmentotopic projection from the spinal cord to the muscle was investigated to evaluate its possible contribution to the compartmental pattern. The most posterior neurones of the EDL motor pool were found to project more frequently to the posterolateral F compartment; similarly, the most anterior neurones most frequently project to the anteromedial K compartment. However, each compartment is innervated by both anteriorly and posteriorly located motoneurones. The segmentotopic projection is too weak to explain the presence of neuromuscular compartments. 3. The post-natal period of synapse elimination appears to play at best a minor role in setting up the compartmentalized innervation. Glycogen depletion and intracellular recording in 1-2-day-old muscles show that each nerve branch innervates fibres in the same region of the muscle as in the adult. Most of the fibres in each compartment are polyneuronally innervated by axons in their own particular nerve branch, although fibres located near the boundary between the two compartments are innervated by axons from both nerve branches. This convergent innervation from the two branches disappears in concert with the elimination of polyneuronal innervation throughout the muscle. A random elimination of these convergent inputs appears adequate to explain the final compartmental pattern. 4. Our findings suggest that the compartmental pattern is primarily the consequence of te segregation of EDL motoneurones into two nerve branches which are directed into separate regions of the muscle.

Animals↗

PubMed1994

Loss of compartmentalization of alveolar tumor necrosis factor after lung injury.

Tumor necrosis factor (TNF), a compartmentalized cytokine, is a key mediator in the systemic inflammatory response syndrome and may play a role in multiorgan failure. To assess whether compartmentalization of alveolar TNF is preserved following lung injury, isolated perfused lungs from Sprague-Dawley rats were given intratracheally 1 ml/kg of phosphate-buffered saline (PBS), 0.1 mg/kg of lipopolysaccharide (LPS), or 125,000 units of murine recombinant TNF (mrTNF). To induce lung leak, one group of rats was given 50 mg/kg of alpha-naphthylthiourea (ANTU) intraperitoneally. Then, 125,000 units mrTNF was given intratracheally to these lungs. Samples of perfusate were assayed for TNF by the L929 cytotoxicity assay before (0 min) and 180 min after the intratracheal challenge, and bronchoalveolar lavage (BAL) was performed for TNF assay. ANTU increased lung leak but intratracheal TNF and LPS did not. The isolated perfused lung preparation expressed small amounts of perfusate TNF and underwent minimal leak that was not caused by TNF release. Endogenous or exogenous intrapulmonary TNF remained predominantly compartmentalized, but following ANTU, TNF readily appeared in the perfusate. Compartmentalization of alveolar TNF is lost during alveolar-capillary injury, suggesting that the injured lung may contribute to a systemic inflammatory response and subsequent multiorgan failure.

Animals↗

PubMed2005

Compartmentalization of massive vascular malformations.

A total of 18 patients with massive vascular malformations of the head and neck region were treated with compartmentalization using nonabsorbable sutures followed by injection of a sclerosant agent into each compartment. The indication for compartmentalization was either to stop potentially uncontrollable, life-threatening hemorrhage during the dissection of the lesion or to reduce its vascularity to allow a less dangerous subsequent resection. Compartmentalization was used in both high-flow and low-flow vascular malformations. In this technique, large nonabsorbable sutures are placed deeply in multiple areas within the lesion. The aim is to divide the malformation into multiple compartments by changing the direction of the suturing; in this way the sclerosing agent is provided with a more effective environment. The sclerosant used was either sodium tetradecyl sulfate 3%, absolute alcohol, or both. The total amount of infiltrate varied from 3 to 35 cc, according to the size of malformation. After compartmentalization, swelling was the most noticeable complication. With this technique, it was possible to treat what were considered untreatable malformations using standard techniques and to control the inevitable serious bleeding.

Adult↗

PubMed1992

Compartmental distribution of ventral striatal neurons projecting to the mesencephalon in the rat.

The ventral striatum is characterized by an intricate neurochemical compartmentation that is reflected in the distribution of most of its afferent fiber systems. In the present study, the compartmental relationships of ventral striatal neurons projecting to the mesencephalon were studied by combining tract tracing with the immunohistochemical localization of leu-enkephalin. Injections of the retrograde tracer cholera toxin subunit B were placed at various sites in the ventral mesencephalon. The anterograde tracer Phaseolus vulgaris leucoagglutinin was injected in single compartments in the rostrolateral part of the nucleus accumbens. The projections from the ventral striatum to the dopaminergic cell groups in the ventral mesencephalon and those to the substantia nigra pars reticulata originate from distinct subpopulations of ventral striatal neurons that respect neurochemically defined compartmental boundaries. In the "shell" of the nucleus accumbens, neurons that project to the dopaminergic cell groups are located outside areas of high cell density and weak enkephalin immunoreactivity (ENK-IR). Rostrolaterally in the "core" of the nucleus accumbens, neurons inside large areas of strong ENK-IR surrounding the anterior commissure project to the dorsomedial part of the substantia nigra pars reticulata, whereas neurons outside these areas innervate the ventral tegmental area and/or the medial part of the substantia nigra pars compacta. By contrast, more caudally in the dorsal part of the nucleus accumbens and in the ventral part of the caudate-putamen, the relationships are reversed: neurons in- or outside small patches of strong ENK-IR project respectively to the pars compacta or the pars reticulata of the substantia nigra. Since the thalamic and cortical afferents of the ventral striatum are compartmentally ordered as well, the present results imply that through the ventral striatal compartments information from disparate combinations of cortical and thalamic sources may be conveyed to distinct mesencephalic targets. The component of the ventral striatomesencephalic system reaching the dopaminergic cell groups A10, A9, and A8 may modulate the dopaminergic input to virtually the entire striatum. The other component can, by way of the pars reticulata of the substantia nigra, participate in nigrothalamic and nigrotectal output pathways of the basal ganglia.

Animals↗