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PubMed2006

A fast learning algorithm for deep belief nets.

We show how to use "complementary priors" to eliminate the explaining-away effects that make inference difficult in densely connected belief nets that have many hidden layers. Using complementary priors, we derive a fast, greedy algorithm that can learn deep, directed belief networks one layer at a time, provided the top two layers form an undirected associative memory. The fast, greedy algorithm is used to initialize a slower learning procedure that fine-tunes the weights using a contrastive version of the wake-sleep algorithm. After fine-tuning, a network with three hidden layers forms a very good generative model of the joint distribution of handwritten digit images and their labels. This generative model gives better digit classification than the best discriminative learning algorithms. The low-dimensional manifolds on which the digits lie are modeled by long ravines in the free-energy landscape of the top-level associative memory, and it is easy to explore these ravines by using the directed connections to display what the associative memory has in mind.

Algorithms↗
PubMed1996

Biphasic response of spinal GABAergic neurons after a lumbar rhizotomy in the adult rat.

The expression of gamma-aminobutyric acid (GABA) and of the isoforms of the enzyme involved in its synthesis, glutamic acid decarboxylase (GAD), is modified in several rat brain structures in different injury models. The aim of the present work was to determine whether such plasticity of the GABAergic system also occurred in the deafferented adult rat spinal cord, a model where a major reorganization of neural circuits takes place. GABAergic expression following unilateral dorsal rhizotomy was studied by means of non-radioactive in situ hybridization to detect GAD67 mRNA and by immunohistochemistry to detect GAD67 protein and GABA. Three days following rhizotomy the number of GAD67 mRNA-expressing neurons was decreased in the superficial layers of the deafferented horn, while GABA immunostaining of axonal fibres located in this region was highly increased. Seven days after lesion, on the other hand, many GAD67 mRNA-expression neurons were bilaterally detected in deep dorsal and ventral layers, this expression being correlated with the increased detection of GAD67 immunostained somata and with the reduction of GABA immunostaining of axons. GABA immunostaining was frequently found to be associated with reactive astrocytes that exhibited intense immunostaining for glial fibrillary acidic protein (GFAP) but remained GAD67 negative. These results indicate that degeneration of afferent terminals induces a biphasic response of GABAergic spinal neurons located in the dorsal horn and show that many spinal neurons located in deeper regions re-express GAD67, suggesting a possible participation of the local GABAergic system in the reorganization of disturbed spinal networks.

Animals↗
PubMedDate not supplied

How does deep brain stimulation work? Present understanding and future questions.

High-frequency deep brain stimulation (DBS) of the thalamus or basal ganglia represents an effective clinical technique for the treatment of several medically refractory movement disorders (e.g., Parkinson's disease, essential tremor, and dystonia). In addition, new clinical applications of DBS for other neurologic and psychiatric disorders (e.g., epilepsy and obsessive-compulsive disorder) have been vaulted forward. Although DBS has been effective in the treatment of movement disorders and is rapidly being explored for the treatment of other neurologic disorders, the scientific understanding of its mechanisms of action remains unclear and continues to be debated in the scientific community. Optimization of DBS technology for present and future therapeutic applications will depend on identification of the therapeutic mechanism(s) of action. The goal of this review is to address the present knowledge of the effects of high frequency stimulation within the central nervous system and comment on the functional implications of this knowledge for uncovering the mechanism(s) of DBS. Four general hypotheses have been developed to explain the mechanism(s) of DBS: depolarization blockade, synaptic inhibition, synaptic depression, and stimulation-induced modulation of pathologic network activity. Using the results from microdialysis, neural recording, functional imaging, and neural modeling experiments, the authors address the main hypotheses and attempt to reconcile what have been considered conflicting results from different research modalities.

Basal Ganglia↗
PubMed2005

Successful declarative memory formation is associated with ongoing activity during encoding in a distributed neocortical network related to working memory: a magnetoencephalography study.

The aim of the present study was to investigate the spatio-temporal characteristics of the neural correlates of declarative memory formation as assessed by the subsequent memory effect, i.e. the difference in encoding activity between subsequently remembered and subsequently forgotten items. Different operations could account for these effects. In particular, it has been proposed that successful memory formation depends on the organization of the information at the time of encoding, an operation accomplished by the working memory system. Consequently, functional magnetic resonance imaging studies have already shown that the very same regions that are involved in certain working memory processes are also involved in declarative memory formation. Here, we used magnetoencephalography to investigate whether the subsequent memory effects in these regions are present throughout picture stimulus presentation, postulating ongoing working memory operations as an effective factor. The results showed that subsequent memory effects began to appear after about 300 ms post stimulus onset over bilateral temporal areas and left parietal regions and were sustained throughout the recording epoch (1000 ms). Roughly parallel to these effects, we identified a left frontal subsequent memory effect, which, however, was less sustained than the other effects. In addition, we revealed a late subsequent memory effect over the right occipital region, which has not been described previously in the event-related potential literature. These sustained subsequent memory effects are suggestive of working memory processes that may enable deep semantic and perceptual processing. Additionally, contextually constrained visual perception after top-down modulation may account for a more efficient encoding of the complex scene.

Adult↗
PubMed2001

Deep brain stimulation of the corpus luysi (subthalamic nucleus) and other targets in Parkinson's disease. Extension to new indications such as dystonia and epilepsy.

Chronic high frequency (130 Hz) stimulation (HFS) of the thalamic target Vim, first used in our group in 1987 as a treatment of tremor of various origins, has been used over the last ten years in 137 patients. Since 1993, this method has been extended to two other targets (subthalamic nucleus (STN): 137 patients and the medial pallidum (GPi): 12 patients), based on recent experimental data in rats and monkeys. STN appears to be a target of major interest, able to control the three cardinal symptoms and to allow the decrease or suppression of levodopa treatment, which then also suppresses levodopa induced dyskinesias. The stereotactic technique is based on the determination of the target using ventriculography, MRI and electrophysiology, with both microrecording of single neuron activity and microstimulation inducing therapeutic symptom suppression and side effects. Chronic electrodes are then placed bilaterally at the best physiologically defined location and then connected to implantable stimulators (either 2 Itrel II or the new double channel Kinetra), operated at 130-185 Hz, 60 ms pulse width, 2.5 to 3.5 volts. There was no operative mortality and permanent morbidity was observed in 3 patients. The mechanisms of action of HFS are not fully understood, but are definitely related to high frequency and are probably different depending on the target. Inhibition of cellular activity or of neural network functions could be induced, by jamming of a retroactive loop for tremor, or by shutdown of neurotransmitter release in STN. Mechanisms within an individual target are also probably different for tremor or for other symptom alleviation. All cardinal symptoms are alleviated from tremor to akinesia and rigidity. This strong improvement allows the decrease of the drug dosage to approximately 30% of the preoperative level, which suppresses the levodopa-induced dyskinesias. The off period dystonias are also suppressed as well as freezings and falls. The effects remain stable over more than 5 years and in the same period, the off stimulation-off medication UPDRS remains stable and does not increase at the usual rate The low rate of permanent complications, the minor side effects and their immediate reversibility, the possibility of bilateral implantation in one session and the long-term persistence of symptom relief are strong arguments which support chronic HFS of STN as the method of choice when a surgical procedure is indicated for the treatment of Parkinson's disease and even more when a bilateral procedure is necessary. Recent data show that STN stimulation could be useful in the treatment of dystonia as well as some forms of epilepsy. It is therefore possible that DBS in STN as well as in other targets could become a potent therapeutic tool in the near future for neurological disorders.

Dystonia↗
PubMedDate not supplied

Simulation of an anatomically defined local circuit: the cone-horizontal cell network in cat retina.

The outer plexiform layer of the retina contains a neural circuit in which cone synaptic terminals are electrically coupled and release glutamate onto wide-field and narrow-field horizontal cells. These are also electrically coupled and feed back through a GABAergic synapse to cones. In cat this circuit's structure is known in some detail, and much of the chemical architecture and neural responses are also known, yet there has been no attempt to synthesize this knowledge. We constructed a large-scale compartmental model (up to 50,000 compartments) to incorporate the known anatomical and biophysical facts. The goal was to discover how the various circuit components interact to form the cone receptive field, and thereby what possible function is implied. The simulation reproduced many features known from intracellular recordings: (1) linear response of cone and horizontal cell to intensity, (2) some aspects of temporal responses of cone and horizontal cell, (3) broad receptive field of the wide-field horizontal cell, and (4) center-surround cone receptive field (derived from a "deconvolution model"). With the network calibrated in this manner, we determined which of its features are necessary to give the cone receptive field a Gaussian center-surround shape. A Gaussian-like center that matches the center derived from the ganglion cell requires both optical blur and cone coupling: blur alone is too narrow, coupling alone gives an exponential shape without a central dome-shaped peak. A Gaussian-like surround requires both types of horizontal cell: the narrow-field type for the deep, proximal region and the wide-field type for the shallow, distal region. These results suggest that the function of the cone-horizontal cell circuit is to reduce the influence of noise by spatio-temporally filtering the cone signal before it passes through the first chemical synapse on the pathway to the brain.

Animals↗
PubMed2001

Prox1 is a marker of ectodermal placodes, endodermal compartments, lymphatic endothelium and lymphangioblasts.

The lymphatic endothelium has mostly been thought to be derived by sprouting from specialized veins. Recently it has been shown that mice deficient for the homeobox transcription factor Prox1 are practically devoid of lymphatics. We have studied the expression of Prox1 mRNA and protein in chick embryos and human fetuses. In the chick, Prox1 is expressed in specific compartments of all germ layers. In the ectoderm, it is found in the neural tube, trigeminal, spinal and sympathetic ganglia and the retina, and also in placodal structures such as the lens, olfactory, otic, facial, glossopharyngeal and vagal placodes, and the apical ectodermal ridge. In the endoderm, Prox1 is a marker of hepatocytes, bile duct and pancreatic epithelium. In the mesoderm, weak expression is observed in cardiomyocytes, and strong expression in lymphatic endothelium. Identical expression domains are found in 19-week-old human fetuses. In day 6.5 chick embryos, there are several sites of contact of lymphatics with the jugular vein, which has a mixed endothelium of Prox1-positive and -negative cells. The only non-lymphatic endothelial cells expressing Prox1 are found on the concave side of the cardiac valves. To further analyse development of lymphatics, we studied early chick embryos and observed scattered Prox1-positive cells in the dermatome, giving rise to Prox1-positive lymphatic networks during subsequent development. Furthermore, the anlagen of the posterior lymph sacs and the paired thoracic duct can already be observed in day-4 chick embryos. Our studies show that lymphatics develop much earlier than previously described, and they mostly do not seem to be derived by sprouting from veins. In contrast, lymphangioblasts are present in the deep and superficial compartments of the early mesoderm, independently giving rise to the deep and superficial lymphatics.

Animals↗
PubMed2004

Projections from the superior colliculus to the trigeminal system and facial nucleus in the rat.

To determine the influence of the superior colliculus (SC) in orienting behaviors, we examined SC projections to the sensory trigeminal complex, the juxtatrigeminal region, and the facial motor nucleus in rats. Anterograde tracer experiments in the SC demonstrated predominantly contralateral colliculotrigeminal projections. Microinjections in the deep layers of the lateral portion showed labeled nerve fibers and terminals in the ventromedial parts of the caudal principal nucleus and of the rostral oral subnucleus and in the medial part of the interpolar subnucleus. Some terminals were also observed in the juxtatrigeminal region and in the dorsolateral part of the facial motor nucleus contralaterally, overlying the orbicularis oculi motoneuronal region. Verification by retrograde tracer injections into the trigeminal target regions showed labeled SC neurons mostly in lateral portions of layers 4-7. When the juxtatrigeminal region was involved, a remarkable increase of labeled neurons was observed, having a patch-like arrangement with a decreasing gradient from lateral to medial SC portions. Retrograde tracer injections in the dorsolateral VII nucleus showed bilateral labeled neurons mainly in the deep lateral SC portion. Retrograde BDA microinjections into the same trigeminal or juxtatrigeminal regions, followed by gold-HRP into the dorsolateral VII nucleus, demonstrated a significant number of SC neurons in deep layers 6-7 projecting to both structures by axon collaterals. These neurons are mediolaterally grouped in patches along the rostrocaudal SC extent; a subset of them are immunoreactive for glutamic acid decarboxylase (GAD). They could be involved in the coordination of facial movements. Simultaneous anterograde and retrograde tracer injections into the lateral SC portion and the VII nucleus respectively localized trigeminofacial neurons receiving collicular input in the trigeminal principal nucleus and pars oralis. Therefore the SC should play a crucial role in regulating motor programs of both eye and eyelid movements.

Animals↗
PubMed2005

Transcranial direct current stimulation of the unaffected hemisphere in stroke patients.

Recovery of function after a stroke is determined by a balance of activity in the neural network involving both the affected and the unaffected brain hemispheres. Increased activity in the affected hemisphere can promote recovery, while excessive activity in the unaffected hemisphere may represent a maladaptive strategy. We therefore investigated whether reduction of the excitability in the unaffected hemisphere by cathodal transcranial direct current stimulation could result in motor performance improvement in stroke patients. We compared these results with excitability-enhancing anodal transcranial direct current stimulation of the affected hemisphere and sham transcranial direct current stimulation. Both cathodal stimulation of the unaffected hemisphere and anodal stimulation of the affected hemisphere (but not sham transcranial direct current stimulation) improved motor performance significantly. These results suggest that the appropriate modulation of bihemispheric brain structures can promote motor function recovery.

Aged↗
PubMed1996

Thalamic collaterals of corticostriatal axons: their termination field and synaptic targets in cats.

Branched cortical projections to the thalamus and striatum were investigated in cats by injecting the retrograde-anterograde tracer biotinylated-dextran amine (BDA) into the caudate nucleus. These injections gave rise to plexuses of labeled fibers and varicosities in widespread thalamic territories. For instance, the lateroposterior nucleus and pulvinar (LP-PUL) mostly contained thick axons that contributed clusters of large-sized varicosities, each forming multiple asymmetric synapses, usually with vesicle-filled dendrites. In contrast, the intralaminar nuclei mostly contained thin axonal segments that emitted small en passant varicosities that formed single asymmetric synapses with spines. Because the caudate nucleus does not project to the thalamus, this labeling had to arise from a neuronal population with branching axons to both structures. Previous findings pointed to three possible sources: brainstem monoaminergic cells, intralaminar thalamic neurons, and corticostriatal cells. The first candidate could be ruled out because monoaminergic neurons contribute small-sized terminals that usually lack membrane specializations. The second possibility was discarded because retrograde tracer injections into the LP-PUL did not give rise to retrograde labeling in the intralaminar nuclear complex but to massive retrograde labeling in deep layers of cortical areas 5 and 7. Therefore, we concluded that the thalamic anterograde labeling originated from corticostriatal neurons, with axons branching to the thalamus. In keeping with this conclusion, Phaseolus vulgaris-leucoagglutinin (PHA-L) injections into cortical areas 5-7 labeled a group of thick corticothalamic fibers that ended in clusters of large boutons in the LP-PUL. These PHA-L-positive terminals were indistinguishable from those labeled after injections of BDA into the caudate nucleus, but they were easy to distinguish from the typical corticothalamic fibers. These findings indicate that the cerebral cortex could coordinate the activity of the striatum and the thalamus via a rich axonal network that collateralizes to both structures. The extent and synaptic organization of this branched projection impose a revision of the traditional scheme of thalamic connectivity.

Animals↗
PubMed1998

Ethanol and neurotransmitter interactions--from molecular to integrative effects.

There is extensive evidence that ethanol interacts with a variety of neurotransmitters. Considerable research indicates that the major actions of ethanol involve enhancement of the effects of gamma-aminobutyric acid (GABA) at GABAA receptors and blockade of the NMDA subtype of excitatory amino acid (EAA) receptor. Ethanol increases GABAA receptor-mediated inhibition, but this does not occur in all brain regions, all cell types in the same region, nor at all GABAA receptor sites on the same neuron, nor across species in the same brain region. The molecular basis for the selectivity of the action of ethanol on GaBAA receptors has been proposed to involve a combination of benzodiazepine subtype, beta 2 subunit, and a splice variant of the gamma 2 subunit, but substantial controversy on this issue currently remains. Chronic ethanol administration results in tolerance, dependence, and an ethanol withdrawal (ETX) syndrome, which are mediated, in part, by desensitization and/or down-regulation of GABAA receptors. This decrease in ethanol action may involve changes in subunit expression in selected brain areas, but these data are complex and somewhat contradictory at present. The sensitivity of NMDA receptors to ethanol block is proposed to involve the NMDAR2B subunit in certain brain regions, but this subunit does not appear to be the sole determinant of this interaction. Tolerance to ethanol results in enhanced EAA neurotransmission and NMDA receptor upregulation, which appears to involve selective increases in NMDAR2B subunit levels and other molecular changes in specific brain loci. During ETX a variety of symptoms are seen, including susceptibility to seizures. In rodents these seizures are readily triggered by sound (audiogenic seizures). The neuronal network required for these seizures is contained primarily in certain brain stem structures. Specific nuclei appear to play a hierarchical role in generating each stereotypical behavioral phases of the convulsion. Thus, the inferior colliculus acts to initiate these seizures, and a decrease in effectiveness of GABA-mediated inhibition in these neurons is a major initiation mechanism. The deep layers of superior colliculus are implicated in generation of the wild running behavior. The pontine reticular formation, substantia nigra and periaqueductal gray are implicated in generation of the tonic-clonic seizure behavior. The mechanisms involved in the recruitment of neurons within each network nucleus into the seizure circuit have been proposed to require activation of a critical mass of neurons. Achievement of critical mass may involve excess EAA-mediated synaptic neurotransmission due, in part, to upregulation as well as other phenomena, including volume (non-synaptic diffusion) neurotransmission. Effects of ETX on receptors observed in vitro may undergo amplification in vivo to allow the excess EAA action to be magnified sufficiently to produce synchronization of neuronal firing, allowing participation of the nucleus in seizure generation. GABA-mediated inhibition, which normally acts to limit excitation, is diminished in effectiveness during ETX, and further intensifies this excitation.

Animals↗
PubMed2000

Time window control: a model for cerebellar function based on synchronization, reverberation, and time slicing.

We present a new hypothesis of cerebellar function that is based on synchronization, delayed reverberation, and time windows for triggering spikes. Our model suggests that granule cells admit mossy fiber activity to the parallel fibers only if the Golgi cells are firing synchronously and if the mossy-fiber spikes arrive within short and well-defined time windows. The concept of time window control organizes neuronal activity in discrete 'time slices' that can be used to discern meaningful information from background noise. In particular, Purkinje cell activity can trigger rebound spikes in deep cerebellar nuclei cells, which project via brain stem nuclei and mossy fibers back to the cerebellar cortex. Using a detailed model of deep cerebellar nuclei cells, we demonstrate that the delayed firing of rebound spikes is a robust mechanism so as to ensure that the reverberated activity re-arrives in the mossy fibers just during the granule-cell time window. Large network simulations reveal that synaptic plasticity (LTD and LTP) at the parallel fiber/Purkinje cell synapses that relies on the timing of the parallel fiber and climbing fiber activities allows the system to learn, store, and recall spatiotemporal patterns of spike activity. Climbing fiber spikes function both as teacher and as synchronization signals. The temporal characteristics of the climbing fiber activity are due to intrinsic oscillatory properties of inferior olivary neurons and to reverberating projections between deep cerebellar nuclei, the mesodiencephalic junction, and the inferior olive. Thus, the reverberating loops of the mossy fiber system and climbing fiber system may interact directly with the time windows provided by the circuitry of the cerebellar cortex so as to generate the appropriate spatio-temporal firing patterns in the deep cerebellar nuclei neurons that control premotor systems. In future studies the model will be extended in that high frequency simple spike activities will be included and that their relevance for motor control will be addressed.

Animals↗
PubMedDate not supplied

Intrinsic circuitry in the deep layers of the cat superior colliculus.

The mammalian superior colliculus is involved in the transformation of sensory signals into orienting behaviors. Sensory and motor signals are integrated in the colliculus to produce movements of the eyes, head, and neck. While there is a considerable amount of information available on the afferent and efferent connections of the colliculus, almost nothing is known about its intrinsic circuitry, particularly that of its deepest layers. It is likely that intrinsic connections in these deeper layers of the colliculus participate in the sensory-motor transformations leading to orienting movements. In this study, we used the neuroanatomical tracer biocytin to label small groups of neurons in the deeper layers of the cat superior colliculus and examine the distribution of their axons and terminals. We found a broadly distributed network of intrinsic projections throughout the deep layers of the superior colliculus. While the majority of terminals were found in a 1-2 mm radius around the injection site, labeled terminals were found throughout the deep layers of the colliculus up to 5 mm from the injection site. In addition, these injections sometimes labeled terminals in the superficial tectum. Extensive projections were demonstrated by the more superficial injections, but few terminals were found when injections were confined to the deepest layers of the colliculus. There was no evidence of anisotropy in the distribution of terminals from injections made at different rostrocaudal or mediolateral locations; neurons located in any one region in the colliculus could potentially influence any other region. This network of intrinsic connections in the cat superior colliculus could provide a means for deeper-layer efferent neurons to associate, and to modulate or coordinate their output. Interneurons could also provide a substrate for mutual inhibition between neurons at the rostral pole of the colliculus that are active during fixation, and more caudally located neurons whose activity is associated with saccadic eye movements.

Animals↗
PubMed2004

Effects of subthalamic nucleus stimulation and medication on resting and postural tremor in Parkinson's disease.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) and antiparkinsonian medication have proved to be effective treatments for tremor in Parkinson's disease. To date it is not known how and to what extent STN DBS alone and in combination with antiparkinsonian medication alters the pathophysiology of resting and postural tremor in idiopathic Parkinson's disease. The purpose of this study was to examine the effects of STN DBS and antiparkinsonian medication on the neurophysiological characteristics of resting and postural hand tremor in Parkinson's disease. Resting and postural hand tremor were recorded using accelerometry and surface electromyography (EMG) from 10 Parkinson's disease patients and 10 matched control subjects. The Parkinson's disease subjects were examined under four treatment conditions: (i) off treatment; (ii) STN DBS; (iii) medication; and (iv) medication plus STN DBS. The amplitude, EMG frequency, regularity, and 1-8 Hz tremor-EMG coherence were analysed. Both STN DBS and medication reduced the amplitude, regularity and tremor-EMG coherence, and increased the EMG frequency of resting and postural tremor in Parkinson's disease. STN DBS was more effective than medication in reducing the amplitude and increasing the frequency of resting and postural tremor to healthy physiological levels. These findings provide strong evidence that effective STN DBS normalizes the amplitude and frequency of tremor. The findings suggest that neural activity in the STN is an important modulator of the neural network(s) responsible for both resting and postural tremor genesis in Parkinson's disease.

Adult↗
PubMed1999

Forebrain connections of medial agranular cortex in the prairie vole, Microtus ochrogaster.

Fluorescent axonal tracers were used to investigate the connections of medial agranular cortex (frontal area 2, Fr2) in male prairie voles. The rostral and caudal portions of Fr2 (rFr2 and cFr2) have distinct but partially overlapping patterns of connections. Thalamic labeling after cFr2 injections was present in anteromedial nucleus (AM), ventrolateral nucleus (VL), lateral segment, mediodorsal nucleus (MDl), centrolateral nucleus (CL), ventromedial nucleus (VM), posterior nucleus (Po) and lateral posterior nucleus (LP). A band of labeled cells involving CL, central medial nucleus (CM) and rhomboid nucleus (Rh) formed a halo around the periphery of submedial (gelatinosus) nucleus (Sm). Within cFr2 there is a rostrocaudal gradient whereby projections from VL and MDl become progressively sparser caudally, whereas those from LP and Po become denser. Rostral Fr2 receives afferents from a similar group of thalamic nuclei, but has denser innervation from VL and MDl, lacks afferents from LP, and receives less input from nuclei around the periphery of Sm. Caudal Fr2 has extensive cortical connections including orbital cortex, rostral Fr2, Fr1, caudal parietal area 1 (Par1), parietal area 2 (Par2), and posterior parietal, retrosplenial and visual areas. Rostral Fr2 has similar connections with areas Fr1, Par1 and Par2; orbital connections focused in ventrolateral orbital cortex (VLO); connections with caudal Fr2; greatly reduced connections with posterior parietal cortex and the visual areas; and no connections with retrosplenial cortex. The axons linking rFr2 and cFr2 with each other and with other cortical areas travel predominately in the deep gray matter of layers VI and VII rather than in the white matter. Projections to the dorsal striatum from rFr2 are widespread in the head of the caudate, become progressively restricted to a dorsocentral focus more caudally, and disappear by the level of the anterior commissure. The projections from cFr2 are largely restricted to a focal dorsocentral region of the striatum and to the dorsolateral margin of the caudatoputamen. In comparison to area Fr2, the laterally adjacent area Fr1 has thalamic and cortical connections which are markedly restricted. Area Fr1 receives thalamic input from nuclei VL, anteroventral nucleus (AV), CL and Po, but none from mediodorsal nucleus (MD) or LP, and its input from VM is reduced. Cortical afferents to Fr1 originate from areas Fr2, caudal Par1 and Par2. Medial agranular cortex of prairie voles has a pattern of connections largely similar to that seen in rats, suggesting that area Fr2 in prairie voles is part of a cortical network that may mediate complex behaviors involving spatial orientation.

Animals↗
PubMed2001

A hybrid input-output approach to model metabolic systems: an application to intracellular thiamine kinetics.

Models of the dynamics of complex metabolic systems offer potential benefits to the deep comprehension of the system under study as well as for the performance of certain tasks. Unfortunately, dynamic modeling of a great deal of metabolic systems may be problematic due to the incompleteness of the available knowledge about the underlying mechanisms and to the lack of an adequate observational data set. In theory, a valid alternative to classical structural modeling through ordinary differential equations could be represented by input-output approaches. But, in practice, such methods, which learn the nonlinear dynamics of the system from input-output data, fail when the experimental data set is poor either in size or in quality. Such a situation is not rare in the case of metabolic systems. This paper deals with a hybrid approach which aims at overcoming the problems addressed above. More specifically, it allows us to solve the identification problems of the intracellular thiamine kinetics in the intestine tissue. The method, which is half way between the structural and input-output approach, uses the outcomes of the simulation of a qualitative structural model to build a good initialization of a fuzzy system identifier. Such an initialization allows us to efficiently cope with both the incompleteness of knowledge and the inadequacy of the available data set, and to derive an input-output model of the intracellular thiamine kinetics in the intestine tissue. The comparison of the predictions of the intracellular thiamine kinetics obtained by the application of such a model with those obtained by traditional approaches, namely compartmental models, neural networks, and fuzzy systems, highlighted a better performance of our model. As the structural assumptions are relaxed, we obtained a model slightly less informative than a purely structural one but robust enough to be used as a simulator. The paper also discusses the interpretative potential offered by such a model, as tested on diabetic subjects.

Animals↗
PubMed1984

An anatomical study of the projections from the dorsal column nuclei to the midbrain in cat.

The termination of the fibers from the dorsal column nuclei (DCN) to the midbrain has been investigated in the cat with the degeneration method, the anterograde horseradish peroxidase (HRP) method and autoradiography after 3H-leucine injections. The results show that the DCN project to several midbrain regions. The external nucleus of the inferior colliculus (IX) receives the heaviest projection from both the gracile and cuneate nuclei. The DCN fibers form three joint terminal zones in IX. Each terminal zone contains clusters with dense aggregations of DCN fibers. Fairly dense terminal networks are found in the posterior pretectal nucleus (PP) and the compact part of the anterior pretectal nucleus (PAc) as well. More scattered DCN fibers are present in the cuneiform nucleus (CF), the lateral part of the periaqueductal gray (PAG1), the red nucleus (NR), the nucleus of the brachium of the inferior colliculus (B), the mesencephalic reticular formation (MRF) and the intermediate and deep layers of the superior colliculus (SI, SP). The projections to all regions are mainly contralateral. Most of the few ipsilateral fibers terminate in IX. A somatotopic organization was seen in IX and NR. The gracile fibers terminate preferentially in the caudal and lateral part of IX and the cuneate ones preferentially in its rostral and medial part. In the red nucleus the gracile fibers terminate ventral to the cuneate ones. In the pretectal region there was a predominance for gracile fibers. There also appeared to be quantitative differences in the projections from various levels of the gracile nucleus, with more midbrain projecting fibers originating in the rostral than in the middle and caudal parts of the nucleus.

Animals↗
PubMed1992

Efferent microvascular responses to electrical stimulation of the area postrema in rats.

As part of its role to transduce blood-borne and afferent neural stimuli to the brain, the area postrema conducts efferent projections monosynaptically to individual nuclei of the medulla oblongata and pons. We hypothesized that electrical activation of the area postrema would mimic this transduction process and couple microvascular responses in efferent sites to local increases in tissue metabolism reported previously. We used quantitative autoradiographic techniques and image analysis to measure capillary transfer constants for [14C]alpha-aminoisobutyric acid (AIB, a small, neutral amino acid) and blood flow (iodo[14C]antipyrine) in individual brainstem structures of anesthetized rats. The area postrema was stimulated electrically by means of a monopolar microelectrode positioned stereotaxically 100 microns deep in the dorsocentral aspect of the organ. There were no significant effects of stimulation on [14C]AIB influx or blood flow in control hindbrain structures where postremal projections are sparse or absent--the spinal trigeminal nucleus, reticular formation, or cerebellar vermis. Stimulation of the area postrema produced equivalent increases in transcapillary influx of [14C]AIB and capillary blood flow in the nucleus of the solitary tract, dorsal motor nuclei of the vagus nerves, ventrolateral medullary C1 region, locus coeruleus, dorsal tegmental nuclei, and lateral parabrachial nuclei. Formation of ratios interrelating rates of [14C]AIB influx and blood flow with previously assessed values of tissue glucose metabolism indicated that these measures increased proportionately during postremal stimulation. Such proportional increases in capillary [14C]AIB transfer and blood flow during tissue activation by area postrema stimulation are consistent with interpretation that the increase in blood flow resulted from recruitment of unused surface area in the capillary networks of individual efferent nuclei.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗