Biomedical subjects

D S Zahm

Publications and source records attributed to D S Zahm.

At least 37 records · Page 2Linked to original sources

PubMed1996

The mediodorsal nucleus of the thalamus in rats--II. Behavioral and neurochemical effects of GABA agonists.

The aim of this study was to determine how GABA receptors in the mediodorsal nucleus of the thalamus in rats might contribute to the regulation of locomotor behavior. Microinjections of the GABAB and GABAA agonists, baclofen and muscimol, into the mediodorsal nucleus produced dose-dependent increases in locomotion that were blocked by co-administration of the GABAB antagonist, 2-hydroxysaclofen. Microinjection of baclofen along the midline, lateral into the ventrolateral thalamus or into the lateral ventricles produced significantly smaller dose-dependent increases in locomotion, indicating that the anatomical locus for baclofen-induced locomotion resides in the mediodorsal nucleus. The motor response elicited by microinjected baclofen was associated with a reduction in dopamine metabolism in the prefrontal cortex and an increase in metabolism in the core of the nucleus accumbens, but not in the accumbal shell or the dorsolateral striatum. These results suggest that GABAergic afferents to the mediodorsal nucleus may oppose a tonic inhibitory tone on locomotor activity. The data also suggest that the motor response produced by baclofen in the mediodorsal thalamus may arise by inhibiting the projections to the prefrontal cortex which modulate mesocorticolimbic dopamine transmission.

Animals↗

PubMed1996

Morphologically distinct subpopulations of neurotensin-immunoreactive striatal neurons observed in rat following dopamine depletions and D2 receptor blockade project to the globus pallidus.

It has been reported in previous studies that perikaryal neurotensin immunoreactivity is largely absent in the rat striatum except following striatal dopamine depletion or blockade of dopamine D2 receptors, after which, however, neurotensin immunoreactivity is elicited in at least two distinct subpopulations of striatal neurons [Zahm D.S. (1992) Neuroscience 46, 335-350]. One subpopulation of such cells (type I), prominent following D2 receptor blockade, is located mainly in the matrix compartment in the rostral, dorsomedial and ventrolateral parts of the striatum, and comprises neurons at the large end of the medium-sized spectrum that exhibit intense neurotensin immunoreactivity in perikarya and proximal dendrites, but rarely display Fos immunoreactivity [Senger B. et al. (1993) Neuroscience 57, 649-660]. A second subpopulation (type II) resides predominantly in the patch (striosome) and matrix compartments in the dorsolateral quadrant of the striatum, and is prominent following administration of reserpine. These neurons are at the small end of the medium size range and exhibit very light neurotensin immunoreactivity, with little staining of dendrites. Fos immunoreactivity is frequently co-localized in striatal neurons that exhibit a type II striatal neurotensin response [Brog J.S. and Zahm D.S. (1995) Neuroscience 65, 71-86]. In the current study, neurotensin immunoreactivity was elicited in striatal neurons by ventral mesencephalic 6-hydroxydopamine lesions or administration of reserpine or haloperidol. Irrespective of which drug was given, retrogradely transported Fluoro-Gold was prominently co-localized with neurotensin-like immunofluorescence in the perikarya of striatal neurons following injections of the retrograde tracer into the globus pallidus. Few double-labeled neurons were observed following administration of any of these drugs and injections of Fluoro-Gold into the substantia nigra. It is concluded that two subpopulations of neurotensin-immunoreactive striatal neurons project predominantly to the globus pallidus and minimally to the substantia nigra.

Animals↗

PubMed1996

Temporal dissociation of neurotensin/neuromedin N mRNA expression in topographically separate subsets of rat striatal neurons following administration of haloperidol.

The expression of the neurotensin/neuromedin N gene in the rat caudate-putamen was studied at 7 and 24 h following the administration of haloperidol using a riboprobe and non-isotopic in situ hybridization histochemistry. As has been reported by others, expression of neurotensin/neuromedin N mRNA in the dorsolateral quadrant of the caudate-putamen was undetectable in controls, robust at 7 h and minimally detectable at 24 h following haloperidol administration. In the dorsomedial and ventrolateral quadrants of the caudate-putamen, barely detectable basal expression of neurotensin/neuromedin N mRNA observed in controls was conspicuously enhanced at 24 h following administration of haloperidol both in terms of numbers of hybridized neurons, which were about 200% of control values, and the amount of chromogen accumulated over individual neurons. The data are consistent with at least two subpopulations of caudate-putamen neurons in which neurotensin/neuromedin N mRNA expression is differentially regulated in response to haloperidol administration.

Animals↗

PubMed1995

Morphometric analysis of ventral mesencephalic neurons retrogradely labeled with Fluoro-Gold following injections in the shell, core and rostral pole of the rat nucleus accumbens.

Morphologically distinct subsets of mesotelencephalic neurons were sought following retrograde transport of Fluoro-Gold from iontophoretic injections relatively restricted to the medial shell, core or rostral pole subterritories of the nucleus accumbens. The diameter and lengths of Fluoro-Gold immunolabeled dendrites of medial shell-projecting neurons were less than those of core and rostral pole-projecting neurons.

Animals↗

PubMed1995

Morphology and Fos immunoreactivity reveal two subpopulations of striatal neurotensin neurons following acute 6-hydroxydopamine lesions and reserpine administration.

It was previously reported that following striatal dopamine depletion or pharmacological blockade of dopamine neurotransmission, neurotensin immunoreactivity is elicited in at least two distinct subpopulations of striatal neurons (Neuroscience Vol. 46, pp. 335-350, 1992). Recently it was shown that Fos immunoreactivity, interpreted as an indicator of enhanced neuronal activity, is appreciably co-localized in only one of the subpopulations of neurotensin-immunoreactive neurons observed following blockade of the dopamine D2 receptor (Neuroscience Vol. 57, pp. 649-660, 1993). In the present study, similar methods were used to determine the degree of co-localization of Fos and neurotensin immunoreactivity in striatal neurons in response to the dopamine-depleting effects of 6-hydroxydopamine lesions and reserpine administration. It was observed that following these treatments, a subpopulation of neurons at the small end of the medium size range exhibited light neurotensin immunoreactivity and frequent co-localization with Fos immunoreactivity. This population was predominant after reserpine administration in the dorsolateral quadrant of the striatum. Another subpopulation comprised larger neurons that exhibited intense neurotensin immunoreactivity in perikarya and proximal processes that was rarely co-localized with Fos immunoreactivity. This type of neuron was observed following all the drug treatments but was present almost to the exclusion of the smaller type of cells three days following ventral midbrain 6-hydroxydopamine lesions, being mainly located in the dorsomedial and ventrolateral portions of the striatum. The present data support the results of the preceding studies in being consistent with the existence of two subpopulations of striatal neurons that accumulate neurotensin following dopamine depletion. The possibility is considered that one subpopulation accumulates neurotensin in response to co-ordinate increases in neuronal activity and neurotensin synthesis, and the other as a result of decreased release.

Animals↗

PubMed1995

Effects of dopamine depletion on the morphology of medium spiny neurons in the shell and core of the rat nucleus accumbens.

Nucleus accumbens receives a dense dopaminergic innervation which is important in regulating motivated states of behavior such as goal-directed actions, stimulus-reward associations and reinforcement of addictive substances. The shell and core territories of this nucleus each receive functionally and morphologically distinct dopaminergic inputs and lesions of the ascending pathways totally deprive the core but not the shell of dopaminergic fibers. Medium spiny neurons are the principal targets of dopaminergic terminals. The present study explored whether the loss of dopamine inputs can affect these neurons and whether cells in the shell and core would be equally susceptible to such a loss. Intracellular injection in fixed slices and neuronal reconstruction were used to analyze the dendritic trees of 62 neurons in the shell and core of animals that received a unilateral, chronic 6-hydroxydopamine lesion of the medial forebrain bundle. In the dopamine-depleted core, dendrites are significantly shorter (16% decrease) than in the intact core and in both the dopamine-depleted core and lateral shell, dendrites are less spiny than in respective control regions. Dopamine loss in the medial shell is associated with significantly more tortuous dendrites that are lower in spine density. However, the number of spines is not reduced which may mean that the increase recorded for segment length, although insignificant in tests, could be responsible for the change in spine density. These data suggest that the loss of dopamine can affect accumbal neuronal morphology and, moreover, can affect neuronal structures differentially in the shell and core.

Animals↗

PubMed1994

Intrathecal capsaicin enhances one-kidney renal wrap hypertension in the rat.

Afferent renal nerves (ARN) have been implicated in the development of one-kidney renal wrap (1K-WRAP) hypertension. The role of renal nerves in desoxycorticosterone acetate-salt (DOCA) hypertension, a low-renin model of hypertension, is controversial. The present study was designed to determine if spinal substance P (SP) and/or calcitonin gene-related peptide (CGRP) in ARN affects the development of 1K-WRAP or DOCA hypertension in adult rats. Selective long-term partial depletion of spinal SP and CGRP within small primary afferent nerve fibers including unmyelinated ARN was achieved by intrathecal administration of capsaicin. After capsaicin treatment, 1K-WRAP hypertension was induced by removing the right kidney and wrapping the left kidney with a figure-8 ligature. In a second group of rats, DOCA hypertension was induced by subcutaneous application of desoxycorticosterone pellets after unilateral nephrectomy. Systolic arterial pressure was monitored for 8 weeks by tail cuff plethysmography after which direct blood pressure measurement was performed followed by immunohistochemistry. Intrathecal capsaicin administration had no significant effect on SP-ir and CGRP-ir of ARN soma located within thoracic dorsal root ganglia whereas immunoreactivity against these peptides was reduced by one third to one half in the dorsal horn, indicating effective long-term spinal depletion of these neuropeptides. Intrathecal capsaicin enhanced the development of 1K-WRAP hypertension, since arterial pressure was greater in the treated group. In contrast, DOCA hypertension was unaffected by capsaicin pretreatment. Considering the neurotoxic action of capsaicin for SP-ir and CGRP-ir unmyelinated primary afferent neurons, we hypothesize that spinal SP, CGRP and/or related peptides existing in ARN and other capsaicin-sensitive unmyelinated primary afferent neurons in the lower thoracic spinal cord may ameliorate 1K-WRAP hypertension, but not DOCA hypertension.

Animals↗

PubMed1994

Immunocytochemical co-localization of substance P and calcitonin gene-related peptide in afferent renal nerve soma of the rat.

Substance P, calcitonin gene-related peptide and somatostatin immunoreactivities have been demonstrated in putative afferent renal nerve fibers in the rat. Utilizing retrograde-tracing and immunohistochemistry, we labeled afferent renal nerve soma throughout dorsal root ganglia T9 to L1. Most (85%) of afferent renal nerve perikarya were immunoreactive for calcitonin gene-related peptide, 21% had substance P immunoreactivity and none had somatostatin immunoreactivity. All renal afferents immunoreactive for substance P also contained calcitonin gene-related peptide. These results provide evidence that calcitonin gene-related peptide and substance P are present and co-localized in afferent renal nerves, and therefore, mediate transmission of afferent renal input to the spinal cord in the rat.

Amidines↗

PubMed1994

Insulin gene expression and insulin synthesis in mammalian neuronal cells.

To demonstrate the presence of de novo synthesis in central mammalian neurons, we cloned and sequenced a rabbit insulin cDNA from pancreas and used it to define sequences encoding insulin mRNA from postnatal rabbit brain. We observed transcription/elongation of nascent insulin transcripts, characterized the size of these transcripts, and localized them to specific neurons in certain catecholaminergic-rich areas of the central nervous system. RNase protection assays using a rabbit probe spanning a region from 14 bases 5' to the translation start site through all but 18 bases of the sequence encoding the A-chain of insulin showed two bands in rabbit brain RNA and only one band in pancreas. The larger band in brain was the same size as that in pancreatic RNA; the other was approximately 10 bases shorter. Because the sequence of a reverse transcription-polymerase chain reaction product from brain RNA was identical to pancreatic RNA sequence in the region corresponding to the 3' region of the probe, the smaller band in brain is most consistent with a sequence mismatch in some brain mRNA in the region corresponding to the 5'-end of the probe. In situ hybridization localized insulin mRNA to anatomical regions involved with olfaction and higher association of the limbic system. High performance liquid chromatography, radioimmunoassay, and [35S]cysteine metabolic labeling of cultured neuronal and glial cells indicated extracellular secretion of immunoprecipitable insulin by neurons only. Presence of insulin transcripts within specific neurons with extracellular secretion of the peptide suggests a specialized biological role.

Aging↗

PubMed1994

Differential foci and synaptic organization of the principal and spinal trigeminal projections to the thalamus in the rat.

The thalamus is known to receive single-whisker 'lemniscal' inputs from the trigeminal nucleus principalis (PrV) and multiwhisker 'paralemniscal' inputs from the spinal trigeminal nucleus (SpV), yet the responses of cells in the thalamic ventroposteromedial nucleus (VPM) are most similar to and contingent upon inputs from PrV. This may reflect a differential termination pattern, density and/or synaptic organization of PrV and SpV projections. This hypothesis was tested in adult rats using anterograde double-labelling with fluorescent dextrans, horseradish peroxidase (HRP) and choleragenoid, referenced against parvalbumin and calbindin immunoreactivity. The results indicated that PrV's most robust thalamic projection is to the whisker-related barreloids of VPM. The SpV had robust projections to non-barreloid thalamic regions, including the VPM 'shell' encapsulating the barreloid area, a caudal and ventral region of VPM that lacks barreloids and PrV inputs, the posterior thalamic nucleus, nucleus submedius and zona incerta. Within the barreloid portion of VPM, SpV projections were sparse relative to those from PrV, and most terminal labelling occurred in the peripheral fringes of whisker-related patches and in interbarreloid septae. Thus, PrV and SpV have largely complementary projection foci in the thalamus. Intra-axonal staining of a small sample of trigeminothalamic axons with whisker or guard hair receptive fields revealed highly localized and somatotopic terminal aggregates in VPM that spanned areas no larger than that of a single barreloid. In the electron microscopic component of this study, HRP transport to the barreloid region of VPM from left SpV and right PrV in the same cases revealed PrV terminals contacting dendrites with a broad range of minor axis diameters (mean +/- SD: 1.51 +/- 0.10 microns). SpV terminals were indistinguishable from those of PrV, but they had a disproportionate number of contacts on narrow dendrites (1.27 +/- 0.07 microns, P < 0.01). PrV endings were also more likely to contact VPM somata (11.0 +/- 4.2% of all labelled terminals) than those from SpV (3.0 +/- 1.0%, P < 0.01). Insofar as primary dendrites are thicker than distal dendrites in VPM, these data suggest a differential distribution of PrV and SpV inputs onto VPM cells that may account for their relative efficacies in dictating the responses of VPM cells to whisker stimulation. Multiwhisker receptive fields in VPM may also reflect direct transmission of convergent inputs from PrV.

Animals↗

PubMed1993

Organization of the proximal, orbital segment of the infraorbital nerve at multiple intervals after axotomy at birth: a quantitative electron microscopic study in rat.

Although much is known of the central consequences of infraorbital nerve (ION) transection at birth, little is known about the effects of this lesion on the organization of the ION itself. To advance our understanding of how deafferentation alters the developing trigeminal neuraxis, 19 newborn rats were subjected to left ION section and perfused 1, 2, 4, 7, 17, or 90 days later. Left IONs were removed in the orbit proximal to the nerve injury site, and axon numbers, types, and fasciculation patterns were assessed with light and electron microscopic methods. Complete axon counts demonstrated that the axotomized ION contained an average (+/- SD) of 13,945 +/- 10,335, 14,112 +/- 3,501, 16,531 +/- 1,904, 9,045 +/- 1,465, 7,018 +/- 4,212, and 8,672 +/- 1,030 axons at the above-listed ages, respectively. These values are well below the 33,059 axons in the normal adult ION (Jacquin et al. [1984] Brain Res. 290:131-135) and the 42,219 axons in the newborn ION (Renehan and Rhoades [1984] Brain Res. 322:369-373). The axotomized ION also contained lower than normal percentages of myelinated axons (26.7% +/- 6.3% on postnatal day 90 vs. 59.7% +/- 6.2% in normal adults). Unmyelinated fibers constituted the vast majority of the remaining fiber types; degenerating fibers never accounted for > 1.6% of all the axons. The number of fascicles making up the axotomized ION overlapped significantly with those found in the normal newborn and adult ION. We conclude that 1) extensive, though variable, axon elimination occurs proximally within one day of the lesion; 2) the 74% reduction in fiber number seen at 90 days is not reliably achieved until postnatal day 7; 3) the higher than normal proportion of unmyelinated axons in the injured ION may underly many of the known effects of neonatal ION injury on the developing whisker-barrel neuraxis; 4) gross changes in ION fasciculation patterns are not prerequisite to injury-induced pattern alterations in the developing trigeminal system.

Animals↗

PubMed1993

The patterns of afferent innervation of the core and shell in the "accumbens" part of the rat ventral striatum: immunohistochemical detection of retrogradely transported fluoro-gold.

Recent data have emphasized the neurochemically distinct nature of subterritories in the accumbens part of the rat ventral striatum termed the core, shell, and rostral pole. In order to gain a more comprehensive understanding of how afferents are distributed relative to these subterritories, immunohistochemical detection of retrogradely transported Fluoro-Gold was carried out following iontophoretic injections intended to involve selectively one of the subterritories. The data revealed that a number of cortical afferents of the medial shell and core originate in separate areas, i.e., the dorsal peduncular, infralimbic, and posterior piriform cortices (to medial shell) and the dorsal prelimbic, anterior agranular insular, anterior cingulate, and perirhinal cortices (to core). The lateral shell and rostral pole are innervated by cortical structures that also project either to the medial shell or core. The orbital, posterior agranular insular, and entorhinal cortices, hippocampus, and basal amygdala were observed to innervate the accumbens in a topographic manner. Following core injections, strong bilateral cortical labeling was observed. Few labeled cortical cells were observed contralaterally following injections in the medial shell. Intermediate numbers of labeled neurons were observed in contralateral cortices following lateral shell injections. Robust subcortical labeling in a variety of structures in the ventral forebrain, lateral hypothalamus, deep temporal lobe, and brainstem was observed after shell injections, particularly those that involved the caudal dorsomedial extremity of the shell, i.e., its "septal pole." Selective ipsilateral labeling of subcortical structures in the basal ganglia circuitry was observed following injections in the core and, to a lesser extent, lateral shell. It was concluded that a number of afferent systems exhibit varying degrees of segregation with respect to the accumbal subterritories.

Afferent Pathways↗

PubMed1993

Specificity in the efferent projections of the nucleus accumbens in the rat: comparison of the rostral pole projection patterns with those of the core and shell.

The efferent connections of the rostral pole of the rat accumbens, where distinct core and shell subterritories can not be identified, were examined with the aid of the anterogradely transported plant lectin, Phaseolus vulgaris-leucoagglutinin (PHA-L), for comparison with the previously reported projection patterns of the accumbal core and shell. Injection sites and transported PHA-L were evaluated with the aid of reference to adjacent sections processed to display substance P or calbindin 28 kD immunoreactivities, i.e., markers that demonstrate the core and shell. Lateral parts of the rostral pole gave rise to a "core-like" projection system that involved the rostroventral globus pallidus, subcommissural ventral pallidum, entopeduncular nucleus and an adjacent part of the lateral hypothalamus, lateral ventral tegmental area, dorsal pars compacta, and structures in the lateral mesencephalic tegmentum and central grey. The medial part of the rostral pole gave rise to a "shell-like" innervation of the subcommissural ventral pallidum, lateral preoptic region, lateral hypothalamus, ventral tegmental area, dorsalmost pars compacta, retrorubral field, lateral midbrain tegmentum, and central grey. In contrast to the large numbers of axon varicosities observed through the entire length of lateral hypothalamus following shell injections, dense accumulations of axon collaterals and varicosities in hypothalamus were limited to the levels of origin of the stria medullaris bundle and entopeduncular nucleus and to the posterlateral region following medial injections. The medial part of the rostral pole contributed some projections to preoptic and sublenticular regions, but not to the bed nucleus of the stria terminalis. Noteworthy concentrations of calbindin immunoreactive cells observed in the lateral rostral pole correlate with the origin of the "basal ganglia-like" projection system, provoking the speculation that ventral striatal calbindin immunoreactive cells contribute principally to basal ganglia-like projections while cells lacking calbindin immunoreactivity contribute to the innervation of hypothalamus and midbrain tegmentum.

Animals↗

PubMed1993

Subsets of neurotensin-immunoreactive neurons in the rat striatal complex following antagonism of the dopamine D2 receptor: an immunohistochemical double-labeling study using antibodies against Fos.

A study was done to determine if the Fos and neurotensin immunoreactivities elicited in the rat striatal complex by the selective dopamine D2 receptor antagonist, S(-)-eticlopride hydrochloride are co-localized in the same neurons. Following injections of eticlopride, Fos and neurotensin immunoreactivity were both non-uniformly distributed among the striatal compartments and subterritories. Fos was co-localized in a significant number of small, lightly neurotensin-immunoreactive neurons, but not in a larger subset of neurons with significantly greater median diameter that exhibited intense neurotensin immunoreactivity extending well into the dendritic arbor. It is proposed that neurotensin-immunoreactive neurons lacking Fos immunoreactivity are prominent following selective blockade of the dopamine D2 receptor and represent a subset of striatal neurotensin-immunoreactive neurons. Neurotensin-immunoreactive cells containing Fos nuclei represent a distinct subset, possibly the one that is dominant following administration of reserpine [Zahm (1992) Neuroscience 46, 335-350]. Insofar as Fos expression has been reported to accompany activation of striatonigral and striatopallidal neurons, the absence of Fos in the subset of neurotensin neurons displayed following D2 receptor blockade may be at odds with activation and perhaps is more consistent with inactivation and accompanying decreased release of neurotensin [see Frey et al. (1988) Neurochem. Int. 12, 33-38, and Bean et al. (1989) J. Neurosci. 9, 4430-4438] as a mechanism underlying the accumulation of neurotensin in that subset of striatal neurons.

Animals↗

PubMed1993

Structure-function relationships in rat brainstem subnucleus interpolaris. X. Mechanisms underlying enlarged spared whisker projections after infraorbital nerve injury at birth.

Prior studies indicate that the central projections of noninfraorbital vibrissae occupy greater than normal transverse areas in the rat trigeminal brainstem complex after infraorbital nerve section at birth. Here, we assessed the development of this phenomenon and possible underlying mechanisms. Cytochrome oxidase patches representing spared supraorbital (SO) or posteroorbital (PO) whiskers in the trigeminal subnucleus interpolaris (SpVi) were not reliably larger than those on the control side 24 hr after the infraorbital lesion. By 72 hr, SO and PO patches were 91% and 28% larger than those on the control side. Reliable increases were also observed on postnatal day 5 (PND5), PND7, and PND10 for the SO (59%, 65%, 66%) and PO (23%, 44%, 51%) patches. To test the hypothesis that central reorganization reflects the maintenance of peripheral supernumerary axons, myelinated and unmyelinated axons in SO vibrissa follicles were counted at PND0, PND7, PND17, and PND60. A corollary hypothesis, that peripheral regeneration errors result in both SO and surviving infraorbital axons, contributing to central SO patches, was tested with retrograde double-labeling methods. Both hypotheses were rejected. Thus, enlargement of SO patches is not due to either the maintenance of an immature peripheral innervation pattern, or regeneration of infraorbital axons into SO follicles. To determine if the enlargement of SO and PO patches produced by infraorbital nerve section is due to an activity-dependent competitive disadvantage imposed upon infraorbital afferents, TTX or bupivicaine was applied to the intact infraorbital nerve over the first 5-9 postnatal days. Brainstem maps developed normally and SO and PO patch areas were unaffected. Thus, impulse activity-based mechanisms do not appear to contribute to injury-induced patch enlargement. To test the hypothesis that patch enlargement is due to central collateral reorganization, intra-axonal recording and staining methods were applied to control and spared-whisker primary afferents in adult rats. Total bouton or collateral numbers did not differ in SpVi; however, arbor areas were reliably larger in experimental (14,879 +/- 350 microns 2) versus control (5527 +/- 1811 microns 2) fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗

PubMed1992

Cholecystokinin concentrations and peptide immunoreactivity in the intact and deafferented medullary dorsal horn of the rat.

To further address the hypothesis that cholecystokinin (CCK) in the medullary dorsal horn (MDH) arises from intrinsic or higher-order neurons, CCK-8-specific radioimmunoassay (RIA) and immunohistochemical (IHC) experiments were carried out in adult rats after trigeminal tractotomy. RIA of punches from deafferented superficial layers of the MDH revealed no significant change in CCK levels vs. the control right side. In this same area, IHC revealed modest reductions in CCK, gastrin, and substance P staining. Calcitonin gene-related peptide (CGRP) staining was reduced substantially. Gastrin immunoreactive cell bodies, present normally in inner lamina II, were reduced in number. RIA and IHC methods were also used to assess MDH CCK concentrations in adult rats subjected to left infraorbital nerve section at birth. The left medulla contained significantly higher levels of CCK than the control right medulla (1.27 +/- 0.19 vs. 0.97 +/- 0.11 ng/mg protein). IHC revealed a dense band of CCK-like staining in laminae I and II ipsi- and contralateral to the lesion. Thus, neonatal deafferentation elevates medullary CCK. To determine if the neonatal lesion-induced increase in medullary CCK is due to primary afferent or higher-order reorganization, RIA and IHC experiments were run after infraorbital nerve section at birth and trigeminal tractotomy in adulthood. RIA revealed no significant change in CCK levels caudal to the tractotomy, although they were higher than control levels in 9 of 12 cases. IHC revealed modest reductions in CCK, substance P, and gastrin staining that resembled the reductions observed in tractotomy-alone cases. These data suggest that 1) most MDH CCK is of non-primary afferent origin, 2) gastrin immunoreactivity in layer II probably originates in CCK-containing cells intrinsic to layer II, the expression of which is dependent upon trigeminal primary afferent input, 3) neonatal V deafferentation induces increased CCK in the superficial MDH, reflecting reorganized intrinsic or higher-order inputs, and 4) higher-order substance P in the MDH is robust.

Animals↗

PubMed1992

Patterns of glucose use after bicuculline-induced convulsions in relationship to gamma-aminobutyric acid and mu-opioid receptors in the ventral pallidum--functional markers for the ventral pallidum.

Bicuculline-induced convulsions increased glucose use throughout the brain and sharply demarcated the ventral pallidum and globus pallidus. Glucose use in the nucleus accumbens also increased after bicuculline-induced convulsions, except for a circumscribed region in the dorsomedial shell. Since the projection from the nucleus accumbens to the ventral pallidum contains gamma-aminobutyric acid (GABA) and the opioid peptide, enkephalin, the pattern of increased glucose use in the ventral pallidum and nucleus accumbens after bicuculline-induced convulsions was compared to the topography of GABAA and mu-opioid receptors. The pattern of glucose use in the nucleus accumbens and ventral pallidum resembled the topography of GABAA, but differed from that of mu-opioid receptors. Bicuculline may disinhibit GABAergic efferents to the ventral pallidum resulting in a dramatic increase in glucose use within striatopallidal synaptic terminals as well as in local terminals of the pallidal projection neurons.

Animals↗

PubMed1992

The neonatal rabbit brain glucose transporter.

The Glut 1 (Hep G2/rat brain) isoform of glucose transporter is expressed in significant amounts in adult mammalian brain. The purpose of our present study was to determine the brain cellular localization of Glut 1 during the late newborn stage of development, when brain cellular proliferation and differentiation is highly active. Employing immunohistochemistry and in-situ hybridization in 10-day-old neonatal rabbit brain sections, we undertook cellular localization of Glut 1 expression. Glut 1 protein and mRNA were mainly noted in considerable amounts within the 10-day-old brain microvasculature. Lower concentrations of Glut 1 immunoreactivity were present in certain glial cells found within the deeper cortical layers of brain. Northern blot analysis of total RNA from isolated microvasculature-enriched preparation, isolated and cultured neuronal and glial cells, whole brain and whole brain with the exclusion of microvasculature obtained from the 10-day-old, revealed the universal presence of a approximately 2.8 kb Glut 1 mRNA with the exception of the neuron-enriched cultures. We conclude that during the neonatal period, when parenchymal cellular proliferation is at a peak, Glut 1 is localized not only to the microvasculature but also to certain cells which express glial morphological characteristics. The neuronal cells either do not express Glut 1 or express minute amounts.

Animals↗