Biomedical subjects

E G Jones

Publications and source records attributed to E G Jones.

At least 55 records · Page 3Linked to original sources

PubMed1998

Changes in subcellular localization of metabotropic glutamate receptor subtypes during postnatal development of mouse thalamus.

High resolution immunoelectron microscopy was used to study subcellular localization patterns of three metabotropic glutamate receptor subtypes (mGluR1alpha, mGluR5, and mGluR2/3) during postnatal development of mouse ventral posterior (VP) thalamic nucleus. Immunoreactivity for all three mGluRs was detected from birth (postnatal day 0, P0), but mGluR1alpha showed dramatic changes in localization with age. In the first postnatal week, mGluR1alpha immunoreactivity was mainly found in proximal dendrites and somata and not usually associated with synaptic contacts. From the second postnatal week, it became concentrated in distal dendrites and preferentially associated with corticothalamic (RS) synapses. mGluR5 immunoreactivity was weaker than mGluR1alpha immunoreactivity at all postnatal ages and showed a similar change in subcellular distribution to that of mGluR1alpha. It was also localized in astrocytic processes. mGluR2/3 immunoreactivity was mainly localized in astrocytic processes surrounding neuronal somata and synapses and this pattern was consistently maintained through all postnatal ages. A small number of presynaptic axon terminals were labeled for mGluR2/3 immunoreactivity and formed asymmetrical synapses. This study demonstrates that Group I mGluR proteins (mGluR1alpha and mGluR5) become redistributed in association with the development of corticothalamic function as demonstrated physiologically, whereas Group II mGluR proteins (mGluR2/3) are mainly associated with neuroglia.

Aging↗

PubMed1998

Early region-specific gene expression during tract formation in the embryonic rat forebrain.

Expression profiles of two recently isolated cDNA fragments, M1 and M2, expressed in the medial telencephalon, were analyzed in developing rat forebrain by in situ hybridization histochemistry and correlative immunocytochemistry. M1 expression was observed in the most ventral portion of the hippocampal rudiment with a sharp dorsal boundary, from embryonic day (E) 12 onward. Its location corresponded to the fimbrial anlage. As the fimbria developed, segregated expression of M1 and neuron-specific class III beta-tubulin or GAP-43 became apparent, suggesting that part of the neuroepithelium producing fimbrial neuroglia expresses M1. M2 expression in the E12 telencephalon was confined to part of the medial cerebral wall, including the presumptive preoptic region and hippocampus, with a diffuse dorsal boundary. At the same stage, M2 expression also occurred in part of the dorsal diencephalon adjacent to the M2-positive telencephalic region, with caudal extension along the dorsal midline, and in the zona limitans intrathalamica. M2 expression domains lacked neuron-specific class III beta-tubulin immunoreactivity. During later stages, M2 expression was found in association with the corpus callosum, hippocampal commissure, fimbria, optic nerve, stria medullaris, tract of the zona limitans, and habenulopeduncular tract. In most cases, M2 expression was detected in regions corresponding to fiber tracts prior to arrival of the earliest axons, which could be detected by TAG-1- or GAP-43 immunohistochemistry. These findings suggest that specialized cell populations express M1 and/or M2 genes in paramedian regions of the forebrain in advance of developing axonal pathways and may be involved in early specification of tract location and differentiation of tract neuroglia.

Animals↗

PubMed1998

Extensive divergence and convergence in the thalamocortical projection to monkey somatosensory cortex.

This study examined the extent of thalamocortical divergence as a potential determinant of activity-dependent representational plasticity in area 3b of adult monkey somatosensory cortex. Single or paired injections of anterogradely transported tracers, of varying anteroposterior extent, were made horizontally from behind in defined parts of the body representation in the ventral posterior lateral (VPL) and/or ventral posterior medial (VPM) thalamic nuclei, and the distribution and density of labeled thalamocortical terminations were mapped in cortex. Injections of increasing size in any dimension of VPL or VPM resulted in increasing accumulation of labeled terminals within the region of projection, implying extensive convergence of individual axons. Anteroposteriorly elongated injections labeled mediolaterally extended but anteroposteriorly restricted zones in cortex. Dorsoventral placement of an injection in VPL or VPM determined anteroposterior location of labeling in cortex. Dual injections separated mediolaterally or dorsoventrally by approximately 1 mm, and in different parts of the thalamic body or head-face representation gave rise to labeled thalamocortical terminations that overlapped extensively. For injection sites at different anteroposterior levels in VPL or VPM, the area of cortical convergence was related to their extent of anteroposterior coincidence. Labeled terminations arising from injections in immediately adjacent parts of VPL and VPM did not overlap in cortex. The extent of thalamocortical divergence and convergence revealed by these experiments is greater than that predictable from labeling of single axons and is sufficiently great to account for representational plasticity that exceeds the 1.5 mm cortical "distance limit."

Animals↗

PubMed1998

GABA(B) receptor gene expression in monkey thalamus.

Expression of gamma-amino butyric acid type B (GABA[B]) receptor gene transcripts was examined in the macaque monkey thalamus by in situ hybridization, using monkey-specific cRNA probes. GABA(B) transcript expression was widespread and of much higher density in the dorsal thalamus than in the reticular nucleus and other parts of the ventral thalamus and was highest in the epithalamus. In the dorsal thalamus, highest mRNA levels were found in the anteroventral nucleus and in the parafascicular nucleus. Sensory relay nuclei showed moderate GABA(B) mRNA levels. Neurons of all sizes were labeled, suggesting expression in relay cells and interneurons, and there was no labeling of neuroglial cells. Following 10-day periods of monocular deprivation, levels of GABA(B) mRNA were decreased in the deprived magno- and parvo-cellular laminae of the dorsal lateral geniculate nuclei, indicating activity-dependent regulation. High levels of GABA(B) receptors in the dorsal thalamus are likely to reflect the high density of synaptic inputs from the reticular nucleus while low expression in the reticular nucleus implies weak, GABA(B)-mediated intrareticular inhibition.

Animals↗

PubMed1998

Cell- and lamina-specific expression and activity-dependent regulation of type II calcium/calmodulin-dependent protein kinase isoforms in monkey visual cortex.

In situ hybridization histochemistry and immunocytochemistry were used to study localization and activity-dependent regulation of alpha, beta, gamma, and delta isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII) and their mRNAs in areas 17 and 18 of normal and monocularly deprived adult macaques. CaMKII-alpha is expressed overall at levels three to four times higher than that of CaMKII-beta and at least 15 times higher than that of CaMKII-gamma and -delta. All isoforms are expressed primarily in pyramidal cells of both areas, especially those of layers II-III, IVA (in area 17), and VI, but are also expressed in nonpyramidal, non-GABAergic cells of layer IV of both areas and in interstitial neurons of the white matter. CaMKII-alpha and -beta are colocalized, suggesting the formation of heteromers. There was no evidence of expression in neuroglial cells. Each isoform has a unique pattern of laminar and sublaminar distribution, but cortical layers or sublayers enriched for one isoform do not correlate with layers receiving inputs only from isoform-specific layers of the lateral geniculate nucleus. CaMKII-alpha and -beta mRNA and protein levels in layer IVC of area 17 are subject to activity-dependent regulation, with brief periods of monocular deprivation caused by intraocular injections of tetrodotoxin leading to a 30% increase in CaMKII-alpha mRNA and a comparable decrease in CaMKII-beta mRNA in deprived ocular dominance columns, especially of layer IVCbeta. Expression in other layers and expression of CaMKII-gamma and delta were unaffected. Changes occurring in layer IVC may influence the formation of heteromers and protect supragranular layers from CaMKII-dependent plasticity in the adult.

Animals↗

PubMed1998

Cell-specific expression of type II calcium/calmodulin-dependent protein kinase isoforms and glutamate receptors in normal and visually deprived lateral geniculate nucleus of monkeys.

In situ hybridization histochemistry and immunocytochemistry were used to map distributions of cells expressing mRNAs encoding alpha, beta, gamma, and delta isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/ kainate receptor subunits, (GluR1-7), and N-methyl-D-aspartate (NMDA) receptor subunits, NR1 and NR2A-D, or stained by subunit-specific immunocytochemistry in the dorsal lateral geniculate nuclei of macaque monkeys. Relationships of specific isoforms with particular glutamate receptor types may be important elements in neural plasticity. CaMKII-alpha is expressed only by neurons in the S laminae and interlaminar plexuses of the dorsal lateral geniculate nucleus, but may form part of a more widely distributed matrix of similar cells extending from the geniculate into adjacent nuclei. CaMKII-beta, -gamma, and -delta isoforms are expressed by all neurons in principal and S laminae and interlaminar plexuses. In principal laminae, they are down-regulated by monocular deprivation lasting 8-21 days. All glutamate receptor subunits are expressed by neurons in principal and S laminae and interlaminar plexuses. The AMPA/kainate subunits, GluR1, 2, 5, and 7, are expressed at low levels, although GluR1 immunostaining appears selectively to stain interneurons. GluR3 is expressed at weak, GluR 6 at moderate and GluR 4 at high levels. NMDA subunits, NR1 and NR2A, B, and D, are expressed at moderate to low levels. GluR4, GluR6 and NMDA subunits are down-regulated by visual deprivation. CaMKII-alpha expression is unique in comparison with other CaMKII isoforms which may, therefore, have more generalized roles in cell function. The results demonstrate that all of the isoforms are associated with NMDA receptors and with AMPA receptors enriched with GluR4 subunits, which implies high calcium permeability and rapid gating.

Animals↗

PubMed1998

Viewpoint: the core and matrix of thalamic organization.

The integration of the whole cerebral cortex and thalamus during forebrain activities that underlie different states of consciousness, requires pathways for the dispersion of thalamic activity across many cortical areas. Past theories have relied on the intralaminar nuclei as the sources of diffuse thalamocortical projections that could facilitate spread of activity across the cortex. A case is made for the presence of a matrix of superficially-projecting cells, not confined to the intralaminar nuclei but extending throughout the whole thalamus. These cells are distinguished by immunoreactivity for the calcium-binding protein, D28K calbindin, are found in all thalamic nuclei of primates and have increased numbers in some nuclei. They project to superficial layers of the cerebral cortex over relatively wide areas, unconstrained by architectonic boundaries. They generally receive subcortical inputs that lack the topographic order and physiological precision of the principal sensory pathways. Superimposed upon the matrix in certain nuclei only, is a core of cells distinguished by immunoreactivity for another calcium-binding protein, parvalbumin, These project in highly ordered fashion to middle layers of the cortex in an area-specific manner. They are innervated by subcortical inputs that are topographically precise and have readily identifiable physiological properties. The parvalbumin cells form the basis for sensory and other inputs that are to be used as a basis for perception. The calbindin cells, especially when recruited by corticothalamic connections, can form a basis for the engagement of multiple cortical areas and thalamic nuclei that is essential for the binding of multiple aspects of sensory experience into a single framework of consciousness.

Animals↗

PubMed1998

Expression of alpha3, beta3 and gamma1 GABA(A) receptor subunit messenger RNAs in visual cortex and lateral geniculate nucleus of normal and monocularly deprived monkeys.

Complementary RNA probes derived from complementary DNA specifically subcloned from monkey tissue were used to localize, by in situ hybridization histochemistry, the relatively rare alpha3, beta3 and gamma1 subunit transcripts of the GABA(A) receptor in visual cortex and lateral geniculate nucleus of normal monkeys and in monkeys that had been deprived of vision in one eye. Overall, levels of alpha3, beta3 and gamma1 subunit transcripts were very low. In the primary visual cortex (area 17) they were concentrated in layers II and VI and in a stratum of white matter subjacent to layer VI. The localization and density of the three messenger RNAs closely resembled those of other rare (alpha2, alpha5 and beta1) transcripts but their distribution also overlapped that of the predominant alpha1, beta2 and gamma2 subunit transcripts. In area 18, alpha3 and beta3 transcript distribution resembled that in area 17, with the addition of a third band of hybridization in layer IV for beta3. Gamma1 subunit transcript localization in area 18 differed significantly from that in area 17, with increased expression restricted to layer IV. In the dorsal lateral geniculate nucleus, beta3 and gamma1 transcripts were expressed at low levels across all layers while alpha3 transcripts were restricted to the magnocellular layers. Following 15 and 18 day periods of monocular deprivation, induced by intravitreal injections of tetrodotoxin, levels of alpha3 receptor subunit transcripts showed modest reductions in layer VI of area 17 and in deprived geniculate laminae of adult animals. Reductions in alpha3 transcript levels were much more pronounced in layer IVCbeta of a five-month-old monkey deprived for the same time. Levels of beta3 and gamma1 transcripts were unaffected by monocular deprivation in cortex and geniculate at any age. Taken together with studies of other GABA(A) receptor transcripts, these results demonstrate the heterogeneity of GABA(A) receptor messenger RNA expression in the monkey geniculo-striate pathway and the varied response to reduced neuronal activity.

Animals↗

PubMed1998

Reciprocal up- and down-regulation of BDNF mRNA in tetanus toxin-induced epileptic focus and inhibitory surround in cerebral cortex.

Chronic focal epilepsy is associated with synaptic plasticity and growth of new connections. Brain-derived neurotrophic factor (BDNF) is associated with each of these processes in normal brain and shows acute up-regulation in models of generalized epilepsy. Here, using an experimental model of focal epilepsy, we show persistent up-regulation of BDNF mRNA, independent of that of other growth factors, in association with the development and persistence of chronic seizures. In situ hybridization histochemistry revealed that rats perfused within 2-3 days after seizure onset had widespread increases in BDNF mRNA levels in the neocortex. Rats perfused at later times, however, showed focal up-regulation of BDNF mRNA at the injection site and down-regulation in a surrounding cortical zone. Nerve growth factor and neurotrophin-3 mRNAs were not significantly altered. These reciprocal changes in BDNF gene expression in the epileptic focus and the cortical surround may contribute to plastic changes in epileptic neuronal circuits that accompany the transition from acute to chronic epilepsy. BDNF down-regulation in the surround is likely to be associated with the inhibitory surround that hampers seizure spread, but facilitates the persistence of a chronic epileptic focus.

Animals↗

PubMed1998

Progression of change in NMDA, non-NMDA, and metabotropic glutamate receptor function at the developing corticothalamic synapse.

The development of receptor function at corticothalamic synapses during the first 20 days of postnatal development is described. Whole cell excitatory postsynaptic currents (EPSCs) were evoked in relay neurons of the ventral posterior nucleus (VP) by stimulation of corticothalamic fibers in in vitro slices of mouse brain from postnatal day 1 (P1). During P1-P12, excitatory postsynaptic conductances showed strong voltage dependence at peak current and at 100 ms after the stimulus and were almost completely antagonized by -2-amino-5-phosphonopentoic acid (APV), indicating that N-methyl--aspartate (NMDA) receptor-mediated currents dominate corticothalamic EPSCs at this time. After P12, in 42% of cells, excitatory postsynaptic conductances showed no voltage-dependence at peak current but still showed voltage-dependence 100-ms poststimulus. This voltage-dependent conductance was antagonized by APV. The nonvoltage-dependent component was APV resistant, showed fast decay, and was antagonized by the nonNMDA antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). In the remaining 58% of cells after P12, excitatory postsynaptic conductances showed moderate voltage dependence at peak conductance and strong voltage dependence 100 ms after the stimulus. Analysis of EPSCs before and after APV showed a significant increase in the relative contribution of the non-NMDA conductance after the second postnatal week. From P1 to P16, there was a significant decrease in the time constant of decay of the NMDA EPSC but no change in the voltage dependence of the NMDA response. After P8, slow EPSPs, 1.5-30 s in duration and mediated by metabotropic glutamate receptors (mGluRs), could be evoked by high-frequency stimulation of corticothalamic fibers in the presence of APV and CNQX. Similar slow depolarizations could be evoked by local application of the mGluR agonist (+/-)-1-aminocyclopentane-trans-1,3-dicarboxylic acid (t-ACPD) but from P0. Both conductances were blocked by the mGluR antagonist, (RS)-alpha-methyl-4-carboxyphenylglycine. Hence functional mGluR receptors are present on VP cells from birth, but their synaptic activation at corticothalamic synapses can only be detected after P8. In voltage clamp, the extrapolated reversal potential of the t-ACPD current, with potassium gluconate-based internal solution, was +12 +/- 10 (SE) mV, and the measured reversal potential with cesium gluconate-based internal solution was 1.5 +/- 9.9 mV, suggesting that the mGluR-mediated depolarization was mediated by a nonselective cation current. Replacement of NaCl in the external solution caused the reversal potential of the current to shift to -18 +/- 2 mV, indicating that Na+ is a charge carrier in the current. The current amplitude was not reduced by application of Cs+, Ba2+, and Cd2+, indicating that the t-ACPD current was distinct from the hyperpolarization-activated cation current (IH) and distinct from certain other previously characterized mGluR-activated, nonselective cation conductances.

2-Amino-5-phosphonovalerate↗

PubMed1998

A new view of specific and nonspecific thalamocortical connections.

Past theories about the circuitry that promotes integration of the whole cerebral cortex and thalamus during forebrain activities that underlie different states of consciousness have relied on the intralaminar nuclei as the sources of diffuse thalamocortical projections that could facilitate spread of activity across many cortical areas. Evidence is presented to show the presence of a matrix of superficially projecting cells extending throughout the whole thalamus that could form a substrate for diffusion of activity across the cortex. The superficially projecting cells in monkeys are distinguished by immunoreactivity for the calcium-binding protein calbindin. They are found in all thalamic nuclei and are increased in some nuclei. They not only project to superficial layers of the cortex but do so over wide areas, unconstrained by boundaries between areas. They are innervated by subcortical inputs that lack the topographic order and physiological precision of the principal sensory pathways. Superimposed on the matrix, but only in certain nuclei, is a core of cells characterized by immunoreactivity for another calcium-binding protein, parvalbumin. These project to middle layers of the cortex in an area-specific and topographically ordered manner. They are innervated by subcortical inputs that are typically precise in having a high degree of topographic order and readily identifiable physiological properties. The parvalbumin cells provide the sensory and other inputs to the cortex that are to be used as a basis for perception. The diffusely projecting calbindin cells can form a basis for the engagement of multiple cortical areas and thalamic nuclei, especially when recruited by corticothalamic connections. Diffusion of activity across multiple areas and thalamic nuclei is essential for the binding of all aspects of sensory experience into a single framework of consciousness.

Animals↗

PubMed1997

Zif268 and Fos-like immunoreactivity in tetanus toxin-induced epilepsy: reciprocal changes in the epileptic focus and the surround.

Altered gene expression for a number of molecules has been suggested as one of the underlying mechanisms of epileptogenesis. Changes in expression of the immediate early genes, zif268 and c-fos, were investigated in chronic focal epilepsy induced by tetanus toxin (TT, 20-35 ng) injected in the rat motor cortex. Most rats injected with TT and perfused on postoperative day 5, 7 or 14 had recurrent focal seizures after a latent period of 4-13 days, and showed enhanced Zif268 immunoreactivity in a cluster of neurons at the injection site, as well as reduced Zif268 immunoreactivity in a distinct cortical zone around this cluster. C-fos or Fos-related immunoreactivity was decreased over widespread areas of frontoparietal and piriform cortex in epileptic rats, except for a focus at the injection site which, in most cases, showed increases in Fos-like immunoreactivity. Some epileptic rats showed increased Zif268 immunoreactivity in neurons of the ipsilateral ventral lateral and central lateral thalamic nuclei and increased Zif268 and Fos-like immunoreactivity in the pontine nuclei. Rats perfused before onset of seizures, showed no overt changes other than a slight decrease in Zif268 and Fos-like immunoreactivity at the injection site. The reciprocal changes in Zif268 immunoreactive neurons in the epileptic focus and the immediate surround parallel changes in gene expression for a number of molecules important in epileptogenesis and suggest a state of functional disconnection of the epileptic focus from other cortical areas that may contribute to the development and maintenance of focal epilepsy.

Animals↗

PubMed1997

Maintenance of a somatotopic cortical map in the face of diminishing thalamocortical inputs.

This study addresses the extent of divergence in the ascending somatosensory pathways of primates. Divergence of inputs from a particular body part at each successive synaptic step in these pathways results in a potential magnification of the representation of that body part in the somatosensory cortex, so that the representation can be expanded when peripheral input from other parts is lost, as in nerve lesions or amputations. Lesions of increasing size were placed in the representation of a finger in the ventral posterior thalamic nucleus (VPL) of macaque monkeys. After a survival period of 1-5 weeks, area 3b of the somatosensory cortex ipsilateral to the lesion was mapped physiologically, and the extent of the representation of the affected and adjacent fingers was determined. Lesions affecting less than 30% of the thalamic VPL nucleus were without effect upon the cortical representation of the finger whose thalamic representation was at the center of the lesion. Lesions affecting about 35% of the VPL nucleus resulted in a shrinkage of the cortical representation of the finger whose thalamic representation was lesioned, with concomitant expansion of the representations of adjacent fingers. Beyond 35-40%, the whole cortical representation of the hand became silent. These results suggest that divergence of brainstem and thalamocortical projections, although normally not expressed, are sufficiently great to maintain a representation after a major loss of inputs from the periphery. This is likely to be one mechanism of representational plasticity in the cerebral cortex.

Animals↗

PubMed1997

Tonotopic organization of auditory cortical fields delineated by parvalbumin immunoreactivity in macaque monkeys.

Tonotopic maps, obtained from single and multi-unit recordings in the primary and surrounding areas of the auditory cortex, were related to chemoarchitecture of the supratemporal plane, as delineated by immunoreactivity for parvalbumin. Neurons in the central core were sharply tuned and formed two complete tonotopic representations corresponding to the primary auditory area (AI) and the rostral (R) area. High frequencies were represented posteriorly in AI and anteriorly in R, the representation reversing in the anterior part of the core. Neurons in regions of less dense immunostaining previously described as lateral (L) and posteromedial (P-m) fields, showed broader frequency tuning. Two tonotopic representations were found in L: in an anterolateral (AL) field, corresponding to a field previously reported by others, high frequencies were represented anteriorly and low frequencies posteriorly; in a posterolateral field (PL) the trend reversed. There was a further reversal on entering P-m from the high frequency representation in PL and progressively lower frequencies tended to be represented more medially in P-m, but P-m may contain two representations reported by others. Neurons in the previously described anteromedial (A-m) and medial (M) fields of weaker immunostaining, were even more broadly tuned. A tonotopic progression from low frequency representation posteriorly to high frequency representation anteriorly was observed in the medial field. Frequency representation in A-m remains uncertain. No tonotopic representation could be demonstrated with the stimuli used in the zones of very weak parvalbumin immunostaining outside AL, PL, P-m, A-m, and M. The properties of neurons in the core and surrounding zones are likely to reflect inputs from the ventral and dorsal medial geniculate nuclei, respectively. The fields outside the core seem to be the starting points for separate streams of auditory corticocortical connections passing into association cortex.

Acoustic Stimulation↗

PubMed1997

Hand/face border as a limiting boundary in the body representation in monkey somatosensory cortex.

Horizontal intracortical connections may form one substrate for representational plasticity in somatosensory cortex. Electrophysiological mapping demonstrated the finer details of the representations of the hand, lower jaw, neck, and face in area 3b of normal macaque monkeys. Injections of two fluorescent tracers then defined the extent to which horizontal connections crossed from the face into the hand representations and vice versa in area 3b. Connections are widely distributed within cortical representations of skin areas innervated by cervical nerves or by the trigeminal nerve but do not cross a border defined by the anterior limit of the representation of skin innervated by the second cervical nerve. This border separates the representation of the muzzle, innervated only by the mandibular nerve, and the representation of the lower jaw and neck region, innervated by the second and third cervical nerves but overlapped by the mandibular nerve. Thus, the muzzle representation lacks connections with the hand and with the lower jaw and neck representations, but the representations of the hand and of the lower jaw and neck are strongly interconnected. Overlap of the hand and of the lower jaw and neck representations and of their horizontal intracortical connections may form one basis for expansions of the lower jaw representation into that of the hand when peripheral input from the hand is lost. Lack of connections with the rest of the face representation may limit this spread.

Afferent Pathways↗

PubMed1997

Differential labeling of dopamine and sigma sites by [3H]nemonapride and [3H]raclopride in postmortem human brains.

The difference between the binding of [3H]nemonapride and [3H]raclopride has been used to quantify dopamine D4 receptors in postmortem schizophrenic brain studies. Recent work, however, has suggested that at least part of the differential between [3H]nemonapride and [3H]raclopride binding may represent sigma rather than D4 receptor sites. We applied the nemonapride-raclopride subtraction method to postmortem, non-schizophrenic human striatum to examine the variation in dopaminergic receptor binding labeled by these ligands. Variation in sigma receptor binding labeled by [3H]nemonapride was studied in frontal cortex, striatum and cerebellum. Specific binding was defined by sulpiride (dopamine receptor ligand), PPAP (sigma receptor ligand) and haloperidol (mixed dopaminergic/sigma agent), respectively. Haloperidol defined a combination of sites, which were approximately the sum of the dopaminergic and sigma components defined by sulpiride and PPAP, respectively. Significant inter-individual variation in the amount of specific binding for dopaminergic and sigma receptor sites was observed. However, no significant nor consistent observation of striatal dopamine D4 receptors or D4-like binding sites was observed in the striatum even though two independent sets of tissues, with different dissections were used. The inconsistencies in some previous postmortem studies appear to be at least partially explained by the inclusion of both sigma and dopaminergic components in [3H]nemonapride binding and the inherent high inter-individual variability of the different components.

Adult↗

PubMed1997

Developmental expression of GABA(A) receptor subunit and GAD genes in mouse somatosensory barrel cortex.

In situ hybridization histochemistry with radioactive cRNA probes was used to study patterns of gene expression for alpha1, alpha2, alpha4, alpha5, beta1, beta2, and gamma2 subunit mRNAs of typeAgamma aminobutyric acid (GABA(A)) receptors and for 67-kDa glutamic acid decarboxylase (GAD67) mRNA in mouse barrel cortex during the period (postnatal days 1-12; P1-P12) when thalamocortical innervation of layer IV barrels is occurring. The alpha1, beta2, and gamma2 subunit mRNAs increased substantially with age, especially in layers V and VI, and throughout the period studied, invariably had the same laminar-specific patterns of expression. All three mRNAs were highly expressed in the dense cortical plate at P1. In layer IV after differentiation of barrels, they were expressed in cells of both barrel walls and hollows but especially in the walls. The alpha2, alpha4, alpha5, and beta1 subunit mRNAs were expressed at lower levels and had different laminar patterns of distribution; alpha2 and alpha4 showed switches between layers over time; alpha5 was invariably associated with the subplate or its derivative, beta1 with layer IV. Levels of alpha2 mRNA did not change over time; alpha4 and beta1 mRNAs increased and alpha5 decreased. GAD67 mRNA was highest in layer I at P1 and progressively increased in other layers. These results suggest that postnatal development of GABA(A) receptors is mainly directed at the production of receptors assembled from alpha1, beta2, and gamma2 subunits, with beta1 contributing in layer IV. Other subunits may be associated with receptors involved in trophic actions of GABA during development and may give GABA(A) receptor-mediated responses in the developing cortex their particular physiological profile.

Animals↗

PubMed1997

Alpha isoform of calcium-calmodulin dependent protein kinase II (CAM II kinase-alpha) restricted to excitatory synapses in the CA1 region of rat hippocampus.

Pre-embedding immunoperoxidase staining for CAM II kinase-alpha and post-embedding immunogold staining for glutamate and GABA, were used to reveal the subcellular distribution of CAM II kinase-alpha at transmitter-characterized synapses in the CA1 region of rat hippocampus. Immunoelectron microscopy showed that the majority of CAM II kinase-alpha-immunostained neuronal profiles were dendritic spines presumably derived from pyramidal cells. CAM II kinase-alpha immunoreactivity was mainly localized in postsynatic densities associated with glutamatergic axon terminals. No CAM II kinase-alpha immunoreactivity was detected in GABA-immunoreactive profiles or at GABAergic synapses. This study provides morphological evidence that CAM II kinase-alpha is involved only in excitatory neuronal transmission in the CA1 region. The enzyme is unlikely to be involved in plasticity at GABA synapses.

Animals↗