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Increased histamine release and granulocytes within the thalamus of a rat model of Wernicke's encephalopathy.

The current study examined the possible role of increased histamine release and granulocyte activity in the vascular changes that precede the onset of necrotic lesions with the thalamus of the pyrithiamine-induced thiamine deficiency (PTD) rat model of Wernicke's encephalopathy (WE). An increase in histamine release and the number of granulocytes was observed in lateral thalamus on day 9 and in medial thalamus on day 10 of PTD treatment, a duration of thiamine deficiency associated with perivascular edema in this brain region. Within the hippocampus, histamine release was significantly increased on day 9, declined to control levels on days 10-12, and was significantly elevated on days 12-14. No granulocytes were observed in hippocampus of either PTD or control rats. These observations suggest that the release of histamine from nerve terminals and histamine and other vasoactive substances from granulocytes may be responsible for thiamine deficiency-induced vascular breakdown and perivascular edema within thalamus.

Animals↗

Measurement of endogenous leucine enkephalin in canine thalamus by high-performance liquid chromatography and field desorption mass spectrometry.

A combination of high-performance liquid chromatography and field desorption mass-spectrometry is used to quantify endogenous amounts of leucine enkephalin in canine thalamus tissue. Reversed-phase high-performance liquid chromatography effects rapid high resolution of brain neuropeptides using a triethylamine formate buffer. An internal standard, 2Ala-leucine-enkephalin, is used. Field desorption mass spectra of neuropeptides generally display only protonated molecular ions. (M + H)+ ion currents of endogenous leucine enkephalin and internal standard were integrated by field desorption mass spectral-selected ion monitoring techniques. The ratio of the two integrated ion currents was used to calculate endogenous amount of leu-enkephalin in thalamus tissue extracts. Leucine enkephalin was determined in this structurally unambiguous fashion in canine thalamus tissue at 50 ng/g thalamus tissue, or the 50 part per billion level.

Animals↗

Effect of CGP 36742 on the extracellular level of neurotransmitter amino acids in the thalamus.

We have evaluated the effect of the brain penetrating GABAb antagonist, CGP 36742 on GABAb receptors using in vivo microdialysis in the ventrobasal thalamus of freely moving rat. When a solution of 1 mM CGP 36742 in ACSF was dialyzed into the ventrobasal thalamus, 2-3-fold increases of extracellular Glu, Asp and Gly running parallel with significant decreases of contralateral extracellular Asp and Gly were observed. Unilateral applications of Glu receptor antagonists (0.5 mM MK801, 0.1 mM CNQX) evoked 2-3-fold decreases of CGP 36742-specific elevations of extracellular Asp, Glu and Gly. Administration of CNQX and MK801 in the absence of CGP 36742 did not alter the extracellular Glu and Gly concentrations whereas extracellular Asp concentrations diminished by 42-45% at both sides. By contrast, no changes of extracellular Gly accompanied the 5-10-fold enhancements of extracellular Asp and Glu, observed during application of the Glu uptake inhibitor, tPDC (1mM). Suspensions of resealed plasmalemma fragments from the rat thalamus were mixed rapidly with the membrane impermeant form of the fluorescence indicator, bis-fura-2 and the changes in fluorescence intensity in response to CGP 36742 (0.5 mM), and the GABAb agonist, baclofen (0.1 mM), were monitored on the time scale of 0.04 ms(-10)s. Progress of CGP 36742-mediated influx, and baclofen-mediated efflux of Ca++ ion, antagonized by CGP 36742, was observed in the 1 ms(-10s) period of time. These data support the hypothesis that background ventrobasal activities and thalamocortical signaling are under the control of inhibitory GABAb receptors in the ventrobasal thalamus.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Modulation of adenylyl cyclase activity by baclofen in the developing rat brain: difference between cortex, thalamus and hippocampus.

Ontogenetic changes in the levels of GABA(B) receptors and their ability to modulate adenylyl cyclase (AC) activity were analyzed in rat cortex, thalamus and hippocampus. The relative numbers of GABA(B) receptors (measured as saturable, high-affinity [(3)H](-)baclofen binding sites) in cortex and thalamus were high already at postnatal day 1 (PD 1) and they reached a maximum at PD 25 and PD 12, respectively. There were no detectable high-affinity [(3)H](-)baclofen binding sites in hippocampus between birth and PD 12 and low-affinity [(3)H](-)baclofen binding attained at PD 12 did not change in adulthood (PD 90). Whereas GTP-stimulated AC activity in cortex and thalamus was depressed by baclofen, it was enhanced in hippocampus. These data indicate that the inhibitory effect of baclofen on AC in cortex and thalamus is primarily mediated through the alpha subunits of G(i)/G(o) proteins. The stimulatory effect of baclofen in hippocampus may be explained by engagement of Gbetagamma subunits.

Adenylyl Cyclases↗

Immunoreactivity for the GABA transporter-1 and GABA transporter-3 is restricted to astrocytes in the rat thalamus. A light and electron-microscopic immunolocalization.

GABA plasma membrane transporters mediate GABA uptake into presynaptic terminals and surrounding glial processes and thus play a key role in shaping the time course and spatial extent of GABA's action. In the present study we have investigated the cellular and subcellular localization of two GABA transporters (1 and 3) in the rat thalamus using affinity-purified polyclonal antibodies. GABA transporter-1 and -3 immunoreactivity, detected with immunoperoxidase and immunofluorescence methods, is present throughout the thalamus in small punctate structures scattered in the neuropil among unlabelled neuronal perikarya. Labelling for GABA transporter-3 is always more intense than that for GABA transporter-1. Astrocytic processes, identified by their immunoreactivity for glial fibrillary acidic protein, express both GABA transporters. Ultrastructural investigations confirm that GABA transporter-1 and -3 labelling is restricted to astrocytes. Labelled astrocytes are adjacent to terminals making either symmetric or asymmetric synaptic contacts, and are close to neuronal profiles that do not form synaptic contacts in the plane of the section. In double-labelled thin sections some GABA transporter-1- or -3-positive astrocytic processes, detected with immunoperoxidase labelling, surround GABA-positive terminals, detected with antibodies to GABA and immunogold labelling. These findings demonstrate that in rat thalamus the GABA uptake system mediated by GABA transporter-1 and -3 is localized exclusively to astrocytes near the synapses and in the neuropil, and absent from GABAergic terminals. Astrocytes play therefore an important role in mediating GABA transmission in the thalamus, compared to cortical regions.

Animals↗

Calretinin immunoreactivity in the developing thalamus of the rat: a marker of early generated thalamic cells.

The present work was aimed to study the immunocytochemical localization of the calcium-binding protein, calretinin, in the rat thalamus from embryonic day 14 to the third postnatal week. In the adult rat thalamus, calretinin immunoreactivity is intensely expressed in some intralaminar and midline nuclei, as well as in selected regions of the reticular nucleus. At embryonic day 14, calretinin was expressed by immature and migrating neurons and fibres laterally to the neuroepithelium of the diencephalic vesicle in the region identified as reticular neuroepithelium. At embryonic day 16, immunoreactive neurons were present in the primordium of the reticular nucleus and in the region of the reticular thalamic migration, where neurons showed the morphology of migratory cells. At the end of embryonic development and in the first postnatal week, calretinin-positive neurons were observed in selected region of the reticular nucleus and it was intensely expressed in some intralaminar and midline nuclei. Bands of immunopositive fibres were also observed crossing the thalamus. During the second postnatal week, the immunolabelling in the reuniens, rhomboid, paraventricular and central medial thalamic nuclei remains very intense while a decrease of immunoreactivity in mediodorsal, centrolateral and laterodorsal nuclei was observed. The immunostaining of fibres, particularly evident in the perinatal period, progressively decreased and it was no longer visible by the end of the second postnatal week when the distribution and intensity of calretinin immunostaining was similar to that observed in the adult rat thalamus. The present findings indicate that the immunolocalization of calretinin can be used to identify subsets of thalamic neuronal population during pre- and postnatal maturation allowing also the detection of the migratory pattern of early generated reticular thalamic neurons.

Aging↗

Adrenergic innervation of the monkey thalamus: an immunohistochemical study.

The distribution and function of the neurotransmitter adrenaline in the primate brain are poorly understood. Biochemical studies have shown the presence of adrenaline or its biosynthetic enzyme, phenylethanolamine-N-methyltransferase, in the rat and human thalamus. However, the distribution of the adrenergic fibres in the thalamus has only been demonstrated in rats. We study the adrenergic innervation of the macaque monkey thalamus using immunohistochemistry against phenyletanolamine-N-methyltransferase. The distribution of phenyletanolamine-N-methyltransferase-immunoreactive fibres is markedly heterogeneous and principally restricted to those nuclei, or their portions, that are located in or close to the midline, with the highest density being found in the paraventricular, parafascicular and mediodorsal nuclei. The paraventricular nucleus is densely innervated by adrenergic axons throughout, while the densest innervation of the parafascicular nucleus is located in its medial part and the strongest mediodorsal nuclear immunolabelling is found in its most posterior and medial region. Moderate or low concentrations of phenyletanolamine-N-methyltransferase-immunopositive fibres are present in the paratenial nucleus, and all parts of the central nucleus, nucleus reuniens, central medial nucleus, centromedian nucleus, medial geniculate body and medial pulvinar nucleus, while only scattered immunoreactive axons are found in other thalamic nuclei. The morphology of the phenyletanolamine-N-methyltransferase-immunoreactive axons is quite diverse, as they have different diameters and most are endowed with diversely-shaped varicosities. These findings are the first morphological evidence for the presence of adrenergic innervation in the primate thalamus and reveal that this innervation is highly selective, heterogeneous and more widely distributed in primates than in rats. The thalamic nuclei innervated by adrenaline are connected to widespread limbic and associative cortical areas as well as to subcortical structures, in particular the neostriatum and amygdala. We hypothesize that thalamic adrenaline may be implicated in emotional, social and attentional mechanisms through its facilitation of co-ordinated action by these brain regions.

Animals↗

Gbx2 expression in the late embryonic chick dorsal thalamus.

The expression pattern of the transcription factor gene Gbx2 in the forebrain of chicken embryos (embryonic day 14) was mapped using digoxigenin-labeled riboprobes and compared with the expression of the transcription factors Pax6 and Nkx2.2. The topographic analysis of Gbx2 expression on coronal and sagittal sections discriminated the positions and boundaries of diverse neuronal nuclei belonging to the dorsal thalamus from neighboring territories (the epithalamus, ventral thalamus, pretectum, and the underlying basal plate). The differential expression of Gbx2 within the dorsal thalamus clearly corresponds with the existence of four primary subdivisions identified in a previous study from this laboratory [13]: the anteroventral region and dorsal, intermediate, and ventral tiers. The subhabenular region turned out not to express Gbx2; this possibly implies it needs to be distinguished as a fifth separate dorsal thalamus subdivision.

Animals↗

Clinical profiles of children with cerebral palsy having lesions of the thalamus, putamen and/or peri-Rolandic area.

Neurological findings, motor symptoms, mental abnormality and dysarthria were examined in 28 children with lesions in the thalamus, putamen, and/or peri-Rolandic area. The thalamus and putamen were involved in eight, and only the thalamus in ten of the children. Most of these 18 children had mild disabilities; they did not have severe mental retardation and could walk alone, speak words, and grasp an object. Dominant flexion of the hips was observed in many of the children who could walk. Two-thirds of these children had athetotic involuntary movement and the remaining had gross or fine motor abnormalities although they had no involuntary movement. In most of these children, reaching patterns were abnormal and were affected by shoulder retraction. Their abnormal movements were thought to be inappropriate muscle activity brought about by voluntary movements. In the remaining ten children, the thalamus, putamen, and peri-Rolandic area were all involved. Many had severe disabilities such as severe mental retardation and the inability to sit, speak words, or grasp an object. All had athetotic involuntary movements. Three children had spasticity of the lower extremities. Five children with severe disabilities and no spasticity were thought to have apparent weakness with athetosis.

Adolescent↗

The distribution of calbindin, calretinin and parvalbumin immunoreactivity in the human thalamus.

UNLABELLED: Calcium-binding proteins show a heterogeneous distribution in the mammalian central nervous system and are useful markers for identifying neuronal populations. The distribution of the three major calcium-binding proteins - calbindin-D28k (calbindin), calretinin and parvalbumin - has been investigated in eight neurologically normal human thalami using standard immunohistochemical techniques. Most thalamic nuclei show immunoreactive cell bodies for at least two of the three calcium-binding proteins; the only nucleus showing immunoreactivity for one calcium-binding protein is the centre médian nucleus (CM) which is parvalbumin-positive. Overall, the calcium-binding proteins show a complementary staining pattern in the human thalamus. In general terms, the highest density of parvalbumin staining is in the component nuclei of the ventral nuclear group (i.e. in the ventral anterior, ventral lateral and ventral posterior nuclear complexes) and in the medial and lateral geniculate nuclear groups. Moderate densities of parvalbumin staining are also present in regions of the mediodorsal nucleus (MD). By contrast, calbindin and calretinin immunoreactivity both show a similar distribution of dense staining in the thalamus which appears to complement the pattern of intense parvalbumin staining. That is, calbindin and calretinin staining is most dense in the rostral intralaminar nuclear group and in the patchy regions of the MD which show very low levels of parvalbumin staining. However, calbindin and calretinin also show low levels of staining in the ventral nuclear complex and in the medial and lateral geniculate bodies which overlaps with the intense parvalbumin staining in these regions. These results show that the calcium-binding proteins are heterogeneously distributed in a complementary fashion within the nuclei of the human thalamus. They provide further support for the concept recently proposed by Jones (Jones, E.G., 1998. VIEWPOINT: the core and matrix of thalamic organization. Neuroscience 85, 331-345) that the primate thalamus comprises of a matrix of calbindin immunoreactive cells and a superimposed core of parvalbumin immunoreactive cells which may have differential patterns of cortical projections.

Adult↗

Nicotinic receptor distribution in the human thalamus: autoradiographical localization of [3H]nicotine and [125I] alpha-bungarotoxin binding.

The thalamus plays a major role in relaying and transforming information that is relayed to the cortex and in turn modulates cortical outputs. The reticular nucleus projects to the other thalamic nuclei, modulating and integrating their activity. The distribution of high affinity nicotine and alpha-bungarotoxin (alpha BTX) receptors in the human thalamus has been investigated by radioligand autoradiography in post mortem human tissue. [3H]nicotine binding in the human thalamus was high in most thalamic nuclei, especially in the lateral dorsal, the medial geniculate, lateral geniculate and anterior nuclei. The distribution of [125I] alpha BTX binding was quite distinct from [3H]nicotine binding. [125I] alpha BTX binding was generally lower (< 0.26-11.62 fmol/mg protein compared with 6.68-36.17 fmol/mg protein for nicotine binding) and concentrated in the reticular nucleus, with discrete groups of cells displaying higher binding in the latter. These results indicate differences between the distribution of nicotinic receptors in humans and those previously reported in mice and monkeys. Changes in high affinity nicotine and alpha BTX receptors in the thalamus may contribute to symptoms observed in neuropathological conditions associated with disorders of perception and movement such as Dementia with Lewy Bodies, Alzheimer's Disease and Schizophrenia.

Adult↗

Magnetic resonance imaging of the thalamus in male patients with schizophrenia.

Thalamic abnormalities have been hypothesized to explain much of the psychopathology in schizophrenia, however, quantitative magnetic resonance imaging (MRI) studies have yielded discrepant results as to whether there are thalamic volume alterations. The current study utilized high resolution MRI and an axial voluming protocol to determine if there was a significant reduction in the volume of the thalamus in patients with schizophrenia. Quantitative analysis was performed on magnetic resonance images of the brain in 41 male medicated schizophrenic patients and 39 male normal control subjects similar in age, education and handedness. There were no group differences in thalamic volumes between controls and patients with schizophrenia, even after adjusting for intracranial volume, total brain tissue volume, and gray matter volume. There were also no significant correlations between thalamic volume and either current neuroleptic dose or illness duration. However, there was a significant right greater than left thalamic volume asymmetry in schizophrenics and controls, and the degree of thalamic volume asymmetry was similar in both groups. The failure to detect any significant difference in thalamic volumes may be due to the heterogeneity of the schizophrenic population and as yet undetermined chronic effects of neuroleptic medication on the thalamus. However, another reasonable explanation for the study findings is that quantitative MRI voluming of the entire thalamus may not be sensitive enough to detect more subtle regional neuropathology within the thalamus.

Adult↗

Independent parcellation of the embryonic visual cortex and thalamus revealed by combinatorial Eph/ephrin gene expression.

The visual cortex in primates is parcellated into cytoarchitectonically, physiologically, and connectionally distinct areas: the striate cortex (V1) and the extrastriate cortex, consisting of V2 and numerous higher association areas [1]. The innervation of distinct visual cortical areas by the thalamus is especially segregated in primates, such that the lateral geniculate (LG) nucleus specifically innervates striate cortex, whereas pulvinar projections are confined to extrastriate cortex [2--8]. The molecular bases for the parcellation of the visual cortex and thalamus, as well as the establishment of reciprocal connections between distinct compartments within these two structures, are largely unknown. Here, we show that prospective visual cortical areas and corresponding thalamic nuclei in the embryonic rhesus monkey (Macaca mulatta) can be defined by combinatorial expression of genes encoding Eph receptor tyrosine kinases and their ligands, the ephrins, prior to obvious cytoarchitectonic differentiation within the cortical plate and before the establishment of reciprocal connections between the cortical plate and thalamus. These results indicate that molecular patterns of presumptive visual compartments in both the cortex and thalamus can form independently of one another and suggest a role for EphA family members in both compartment formation and axon guidance within the visual thalamocortical system.

Animals↗

Single trial fMRI reveals significant contralateral bias in responses to laser pain within thalamus and somatosensory cortices.

Pain is processed in multiple brain areas, indicating the complexity of pain perception. The ability to locate pain plays a pivotal role in immediate defense and withdrawal behavior. However, how the brain localizes nociceptive information without additional information from somatotopically organized mechano-receptive pathways is not well understood. We used single-trial functional magnetic resonance imaging (fMRI) to assess hemodynamic responses to right and left painful stimulation. Thulium-YAG-(yttrium-aluminium-granate)-laser-evoked pain stimuli, without concomitant tactile component, were applied to either hand in a randomized order. A contralateral bias of the BOLD response was investigated to determine areas involved in the coding of the side of stimulation, which we observed in primary (SI) and secondary (SII) somatosensory cortex, insula, and the thalamus. This suggests that these structures provide spatial information of selective nociceptive stimuli. More importantly, this contralateral bias of activation allowed functionally segregated activations within the SII complex, the insula, and the thalamus. Only distinct subregions of the SII complex, the posterior insula and the lateral thalamus, but not the remaining SII complex, the anterior insula and the medial thalamus, showed a contralaterally biased representation of painful stimuli. This result supports the hypothesis that sensory-discriminative attributes of painful stimuli, such as those related to body side, are topospecifically represented within the forebrain projections of the nociceptive system and highlights the concept of functional segregation and specialization within these structures.

Adult↗

Sleep stage dependant changes of the high-frequency part of the somatosensory evoked potentials at the thalamus and cortex.

OBJECTIVES: It is known that the high-frequency oscillations (above 400 Hz) of the somatosensory evoked potentials (SEPs) diminish during sleep while the N20 persists (Neurology 38 (1988) 64; Electroenceph clin Neurophysiol 70 (1988) 126; Electroenceph clin Neurophysiol 100 (1996) 189). We investigated possible differential effects of sleep on the 600 Hz SEPs at the thalamus and cortex. METHODS: SEPs from 10 subjects were recorded using 64 channels following electric stimulation at the wrist during awake state and sleep stages II, IV and REM. Dipole source analysis was applied to separate brain-stem, thalamic and cortical activity in the low-frequency (20-450 Hz) and the high-frequency (450-750 Hz) part of the signal. RESULTS: The low-frequency SEPs showed a non-significant increase of the latency of the N20 and a bifid change of the waveform in 3 subjects. The high-frequency SEPs showed a significant decrease of their amplitude at the level of the thalamus and cortex but not at the brain-stem. This decrease in amplitude at the thalamus and cortex were significantly correlated. There was no effect on the latency of the signal. In addition, at the cortex, differential effects on early and late parts of the 600 Hz oscillations were found by time-frequency analysis using a wavelet transformation. CONCLUSIONS: Sleep dependent decrease of the high-frequency SEPs were first observed at the thalamus pointing to the known function of the reticular thalamic nucleus regulating arousal. The results presented here provide further evidence for a thalamic origin of the 600 Hz oscillations. In addition, on the basis of the differential effects on early (up to the N20 peak) and late (between 20 and 25 ms) parts of the signal, at least one intracortical generator of these oscillations is proposed. In general, the high-frequency SEPs (600 Hz oscillations) are supposed to reflect activity of a somatosensory arousal system.

Adult↗

Bilateral lesions of thalamus and basal ganglia: origin and outcome.

Twenty-seven MRI examinations from 17 children (7 females, 10 males) with bilateral lesions of the basal ganglia and thalamus, presenting over a period of 8 years, were reevaluated, and correlated with the type of cerebral palsy (CP) as well as motor and cognitive impairment. Children were between 1 year 6 months and 17 years old at last examination (mean 5 years 9 months). Brain damage had occurred as a consequence of birth asphyxia in nine patients and of neonatal shock in four patients. No adverse event could be identified in four children. In these, late prenatal compromise is assumed, as extensive screening (including MR spectroscopy in two patients) did not yield an underlying metabolic disorder. Three different degrees of MRI lesion patterns could be defined: a mild pattern (involvement of nucleus lentiformis and ventro-lateral thalamus only; n=7), an intermediate pattern (involvement of nucleus lentiformis, ventro-lateral thalamus, and pericentral region; n=3), and a severe pattern (involvement of nucleus lentiformis, entire thalamus, pericentral region, and hippocampus; n=7). This grading of MRI findings correlated significantly with the severity of both cognitive and motor impairment and type of CP. Normal cognitive development and mild motor delay was only seen with the mild pattern. All children developed CP: purely dyskinetic CP was only seen with the mild pattern, whereas the dyskinetic-spastic or spastic CP types could be seen in all three lesion patterns, with dyskinetic-spastic CP more related to the moderate, and purely spastic CP more related to the severe pattern.

Adolescent↗

Retinal ganglion cells projecting to the optic tectum and visual thalamus of lizards.

Retinal ganglion cells projecting to the optic tectum and visual thalamus have been investigated in the lizard, Podarcis hispanica. Injections of biotinylated dextran-amine in the optic tectum reveal seven morphological cell varieties including one displaced ganglion cell type. Injections in the visual thalamus yield similar ganglion cell classes plus four giant ganglion cells, including two displaced ganglion cell types. The present study constitutes the first comparison of tectal versus thalamic ganglion cell types in reptiles. The situation found in lizards is similar to that reported in mammals and birds where some cell types projecting to the thalamus are larger than those projecting to the mesencephalic roof. The presence of giant retino-thalamic ganglion cells with specific dendritic arborizations in sublaminae A and B of the inner plexiform layer suggests that parts of the visual thalamus of lizards could be implicated in movement detection, a role that might be played by the ventral lateral geniculate nucleus, which is involved in our tracer injections.

Animals↗

Glial organization and chondroitin sulfate proteoglycan expression in the developing thalamus.

This study examines the early organization of glial cells, together with the expression of chondroitin sulfate proteoglycans in the developing thalamus of ferrets. Glia were identified with antibodies against vimentin and glial fibrillary acidic protein and the chondroitin sulfate proteoglycans were identified by using an antibody against chondroitin sulfate side chains. Our results reveal three striking features of early thalamic development. First, there is a distinct population of glial fibrillary acidic protein-immunoreactive astrocytes (first seen at E30) that resides in the perireticular thalamic nucleus of the primordial internal capsule. These glial fibrillary acidic protein-immunoreactive astrocytes of the perireticular nucleus are transient and form a conspicuous feature of the early developing forebrain. They are first apparent well before any glial fibrillary acidic protein-immunoreactive astrocytes are seen in other regions of the thalamus (at about P8). Further, unlike in other thalamic regions, these peculiar perireticular astrocytes do not express vimentin before they express glial fibrillary acidic protein. Second, in the reticular thalamic nucleus, the radial glial cells express glial fibrillary acidic protein; they are the only ones to do so in the thalamus during development. The glial fibrillary acidic protein-immunoreactive radial glial cells of the reticular nucleus form a rather distinct band across the developing thalamus at these early stages (E30-P1). Finally, and preceding the expression of glial fibrillary acidic protein, the radial glial cells of the reticular nucleus, unlike those in other thalamic regions, are associated closely with the expression of chondroitin sulfate proteoglycans (E20-E30). Later (after E30), the expression of the chondroitin sulfate proteoglycans in the reticular nucleus declines sharply. The significance of this finding is related to the early organization of the cortico-fugal and cortico-petal pathways.

Aging↗