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E A Grove

Publications and source records attributed to E A Grove.

15 recordsLinked to original sources
PubMed1999

Patterning events and specification signals in the developing hippocampus.

The mouse hippocampus is an attractive model system in which to study patterning of a cortical structure. Ongoing studies indicate that hippocampal areas or fields are specified many days before birth -- possibly involving signals from within the cortical mantle. Although the hippocampal CA fields are distinguished by cytoarchitecture only after birth, molecular differences between fields appear by late gestation. Moreover, these embryonic fields are already specified to develop additional features that characterize the mature fields. The basic division of the hippocampus into fields may be specified still earlier. Thus, if medial cortical neuroepithelium is isolated in vitro early in hippocampal neurogenesis, it can autonomously generate features of a patterned hippocampus. In vivo, the spatial progression of initial field differentiation suggests that signals regulating growth and patterning could arise from sources close to the hippocampal poles. Observations of mouse mutants indicate that the cortical hem, an embryonic structure close to one pole of the hippocampus, is a source of such regulatory signals.

Age Factors↗
PubMed1998

The hem of the embryonic cerebral cortex is defined by the expression of multiple Wnt genes and is compromised in Gli3-deficient mice.

In the developing vertebrate CNS, members of the Wnt gene family are characteristically expressed at signaling centers that pattern adjacent parts of the neural tube. To identify candidate signaling centers in the telencephalon, we isolated Wnt gene fragments from cDNA derived from embryonic mouse telencephalon. In situ hybridization experiments demonstrate that one of the isolated Wnt genes, Wnt7a, is broadly expressed in the embryonic telencephalon. By contrast, three others, Wnt3a, 5a and a novel mouse Wnt gene, Wnt2b, are expressed only at the medial edge of the telencephalon, defining the hem of the cerebral cortex. The Wnt-rich cortical hem is a transient, neuron-containing, neuroepithelial structure that forms a boundary between the hippocampus and the telencephalic choroid plexus epithelium (CPe) throughout their embryonic development. Indicating a close developmental relationship between the cortical hem and the CPe, Wnt gene expression is upregulated in the cortical hem both before and just as the CPe begins to form, and persists until birth. In addition, although the cortical hem does not show features of differentiated CPe, such as expression of transthyretin mRNA, the CPe and cortical hem are linked by shared expression of members of the Bmp and Msx gene families. In the extra-toesJ (XtJ) mouse mutant, telencephalic CPe fails to develop. We show that Wnt gene expression is deficient at the cortical hem in XtJ/XtJ mice, but that the expression of other telencephalic developmental control genes, including Wnt7a, is maintained. The XtJ mutant carries a deletion in Gli3, a vertebrate homolog of the Drosophila gene cubitus interruptus (ci), which encodes a transcriptional regulator of the Drosophila Wnt gene, wingless. Our observations indicate that Gli3 participates in Wnt gene regulation in the vertebrate telencephalon, and suggest that the loss of telencephalic choroid plexus in XtJ mice is due to defects in the cortical hem that include Wnt gene misregulation.

Animals↗
PubMed1997

Early specification and autonomous development of cortical fields in the mouse hippocampus.

Studies of the specification of distinct areas in the developing cerebral cortex have until now focused mainly on neocortex. We demonstrate that the hippocampus, an archicortical structure, offers an elegant, alternative system in which to explore cortical area specification. Individual hippocampal areas, called CA fields, display striking molecular differences in maturity. We use these distinct patterns of gene expression as markers of CA field identity, and show that the two major hippocampal fields, CA1 and CA3, are specified early in hippocampal development, during the period of neurogenesis. Two field-specific markers display consistent patterns of expression from the embryo to the adult. Presumptive CA1 and CA3 fields (Pca1, Pca3) can therefore be identified between embryonic days 14.5 and 15.5 in the mouse, a week before the fields are morphologically distinct. No other individual cortical areas have been detected by gene expression as early in development. Indeed, other features that distinguish between the CA fields appear after birth, indicating that mature CA field identity is acquired over at least 3 weeks. To determine if Pca1 and Pca3 are already specified to acquire mature CA field identities, the embryonic fields were isolated from further potential specification cues by maintaining them in slice culture. CA field development proceeds in slices of the entire embryonic hippocampus. More strikingly, slices restricted to Pca1 or Pca3 alone also develop appropriate mature features of CA1 or CA3. Pca1 and Pca3 are therefore able to develop complex characteristics of mature CA field identity autonomously, that is, without contact or innervation from other fields or other parts of the brain. Because Pca1 and Pca3 can be identified before major afferents grow into the hippocampus, innervation may also be unnecessary for the initial division of the hippocampus into separate fields. Providing a clue to the source of the true specifying signals, the earliest field markers appear first at the poles of the hippocampus, then progress inwards. General hippocampal development does not follow this pronounced pattern. We suggest that the sources of signals that specify hippocampal field identity lie close to the hippocampal poles, and that the signals operate first on cells at the poles, then move inwards.

Animals↗
PubMed1993

Multiple restricted lineages in the embryonic rat cerebral cortex.

We have labelled precursor cells in the embryonic rat cerebral cortex using BAG, a retroviral vector that expresses beta-galactosidase. We had previously reported that labelled precursor cells generate clusters of labelled cells that could be classified into four types by their morphological appearance and anatomical distribution (Price and Thurlow, 1988). In this study, we have used immunohistochemistry and intracellular dye labelling to identify the cell types that make up these clusters. We discovered that clusters are almost always composed of a single cell type. In addition to clusters composed entirely of neurones, we found four different types of glial cell clusters. In the grey matter, glial clusters are composed either of protoplasmic astrocytes, or of cells that have an astrocyte morphology, but no glial filaments. In the white matter, clusters are composed of either fibrous astrocytes or oligodendocytes. Our results indicate that each of these different cortical cell types is generated from a separate population of precursor cells.

Animals↗
PubMed1992

Neuronal precursor cells in the rat hippocampal formation contribute to more than one cytoarchitectonic area.

We have tested the hypothesis that cell lineage restriction boundaries define the borders between cytoarchitectonic areas in the cerebral cortex. Clonally related cells were identified using a retroviral marking technique, and the dispersion of neuronal clones was examined with respect to the transitions between cortical areas. We chose to study the hippocampal formation because we found that clones of hippocampal neurons, unlike those in neocortex, are compact and readily identifiable in the adult and that transitions between areas in the hippocampus are sharp relative to the spread of a typical clone. We conclude, contrary to the hypothesis, that clones of neurons transgress the boundaries between areas in the hippocampal formation, that border-crossing clones are observed as frequently as would be expected if clones spread freely over the hippocampus with no constraint imposed by area borders, and that different types of pyramidal neurons, characteristic of different areas, may appear to a single clone. different areas, may appear in a single clone.

Animals↗
PubMed1990

Inhibition of protein kinase C prevents phorbol ester- but not muscarine-induced depolarizations in the rat superior cervical ganglion.

The role of protein kinase C (PKC) activation in mediating muscarinic depolarization was assessed in the rat superior cervical ganglion. Staurosporine, an inhibitor of PKC, abolished a depolarization elicited by the direct PKC activator beta-phorbol 12,13-dibutyrate, but had little effect on the response to muscarine. Thus, activation of PKC may not be an obligatory transduction step between muscarinic receptor stimulation and depolarization.

Action Potentials↗
PubMed1989

9-Amino-1,2,3,4-tetrahydroacridine (THA) blocks agonist-induced potassium conductance in rat hippocampal neurones.

The actions of 9-amino-1,2,3,4-tetrahydroacridine (THA) were studied on rat CA1 pyramidal neurones under voltage-clamp in transverse slices of hippocampus maintained in vitro. As previously reported, THA reduced the resting conductance of cells; THA also suppressed inward rectification activated by hyperpolarization by up to 75% (The dose of THA which reduced the response by 50% (IC50) was 300 microM). More sensitive to the action of THA was the outward K+ current activated in CA1 neurones by 5-HT, adenosine and baclofen. This was completely blocked by THA (IC50 = 28 microM). The cooperativity of this latter action of THA with its well-known anticholinesterase activity is discussed in relation to the therapeutic effects of THA in treating Alzheimer's disease.

Adenosine↗
PubMed1988

Neural associations of the substantia innominata in the rat: afferent connections.

The afferent connections of the substantia innominata (SI) in the rat were determined employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP), in combination with histochemical procedures to characterize the neuropil of the SI and identify cholinergic cells. Both neurochemical and connectional data establish that the SI is organized into a dorsal and a ventral division. Each of these divisions is strongly affiliated with a different region of the amygdala, and, together with its amygdalar affiliate, forms part of one of two largely distinct constellations of interconnected forebrain and brainstem cell groups. The dorsal SI receives selective innervation from the lateral part of the bed nucleus of the stria terminalis, the central and basolateral nuclei of the amygdala, the fundus of the striatum, distinctive perifornical and caudolateral zones of the lateral hypothalamus, and caudal brainstem structures including the dorsal raphe nucleus, parabrachial nucleus, and nucleus of the solitary tract. Projections preferentially directed to the ventral SI arise from the medial part of the bed nucleus of the stria terminalis, the rostral two-thirds of the medial nucleus of the amygdala, a large region of the rat amygdala that lies ventral to the central nucleus, the medial preoptic area, anterior hypothalamus, medialmost lateral hypothalamus, and the ventromedial hypothalamus. Both SI divisions appear to receive afferents from the dorsomedial and posterior hypothalamus, supramammillary region, ventral tegmental area, and the peripeduncular area of the midbrain. Projections to the SI whose selectivity was not determined originate from medial prefrontal, insular, perirhinal, and entorhinal cortex and from midline thalamic nuclei. Findings from both PHA-L and WGA-HRP experiments additionally indicate that cell groups preferentially innervating a single SI division maintain numerous projections to one another, thus forming a tightly linked assembly of structures. In the rat, cholinergic neurons that are scattered throughout the SI and in parts of the globus pallidus make up a cell population equivalent to the primate basal nucleus of Meynert (Mesulam et al.: Neuroscience 10:1185-1201, '83). PHA-L-filled axons, labelled from lectin deposits in the dorsal raphe nucleus, peripeduncular area, ventral tegmental area, or caudomedial hypothalamus were occasionally seen to approach individual cholinergic neurons int he SI, and to contact the surface of such cells with axonal varicosities (putative synaptic boutons.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways↗
PubMed1988

Efferent connections of the substantia innominata in the rat.

The efferent connections of the substantia innominata (SI) were investigated employing the anterograde axonal transport of Phaseolus vulgaris leucoagglutinin (PHA-L) and the retrograde transport of wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). The projections of the SI largely reciprocate the afferent connections described by Grove (J. Comp. Neurol. 277:315-346, '88) and thus further distinguish a dorsal and a ventral division in the SI. Efferents from both the dorsal and ventral divisions of the SI descend as far caudal as the ventral tegmental area, substantia nigra, and peripeduncular area, but projections to pontine and medullary structures appear to originate mainly from the dorsal SI. Within the amygdala and hypothalamus, which receive widespread innervation from the SI, the dorsal SI projects preferentially to the lateral part of the bed nucleus of the stria terminalis; the lateral, basolateral, and central nuclei of the amygdala; the lateral preoptic area; paraventricular nucleus of the hypothalamus; and certain parts of the lateral hypothalamus, prominently including the perifornical and caudolateral zones described previously. The ventral SI projects more heavily to the medial part of the bed nucleus of the stria terminalis; the anterior amygdaloid area; a ventromedial amygdaloid region that includes but is not limited to the medial nucleus; the lateral and medial preoptic areas; and the anterior hypothalamus. Modest projections reach the lateral hypothalamus, with at least a slight preference for the medial part of the region, and the ventromedial and arcuate hypothalamic nuclei. Both SI divisions appear to innervate the dorsomedial and posterior hypothalamus and the supramammillary region. In the thalamus, the subparafascicular, gustatory, and midline nuclei receive a light innervation from the SI, which projects more densely to the medial part of the mediodorsal nucleus and the reticular nucleus. Cortical efferents from at least the midrostrocaudal part of the SI are distributed primarily in piriform, infralimbic, prelimbic, anterior cingulate, granular and agranular insular, perirhinal, and entorhinal cortices as well as in the main and accessory olfactory bulbs. The cells of origin for many projections arising from the SI were identified as cholinergic or noncholinergic by combining the retrograde transport of WGA-HRP with histochemical and immunohistochemical procedures to demonstrate acetylcholinesterase activity or choline acetyltransferase immunoreactivity. Most of the descending efferents of the SI appear to arise primarily or exclusively from noncholinergic cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Changes in helper and suppressor T lymphocytes following radiotherapy for breast cancer.

Changes in total lymphocyte, T lymphocyte, T helper and T suppressor lymphocyte numbers were studied in 22 patients with breast cancer before and after radiotherapy. T lymphocyte subsets were measured using monoclonal antibodies and fluorescence microscopy. After treatment the total lymphocyte count fell significantly and was still reduced 9 months later, but the proportion of cells labelled as T lymphocytes was unchanged during this period. The helper-suppressor ratio, which was within the normal range before radiotherapy, was significantly reduced at 3 months and 9 months after. Following treatment both T helper and T suppressor cell numbers were significantly reduced. T helper cell numbers remained reduced throughout the study period but T suppressor cell numbers showed a recovery to normal values 9 months after radiotherapy.

Breast Neoplasms↗
PubMed1986

Light microscopic evidence of striatal input to intrapallidal neurons of cholinergic cell group Ch4 in the rat: a study employing the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L).

Injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) were placed in various striatal loci in the rat. Within the globus pallidus, PHA-L-filled striatofugal axons were seen to approach cholinergic neurons, identified with either acetylcholinesterase histochemistry or choline acetyltransferase immunohistochemistry, and, apparently, to contact the surface of such cells with axonal varicosities. Since these varicosities are thought to mark the sites of synaptic terminals, such juxtapositions provide strong light-microscopic evidence that intrapallidal cholinergic neurons in the rat receive a direct innervation from the striatum and are integrated into the circuitry of the basal ganglia.

Acetylcholinesterase↗
PubMed1985

Efferent connections of the ventral pallidum: evidence of a dual striato pallidofugal pathway.

Previous histological and histochemical studies have provided evidence that the globus pallidus (external pallidal segment) as conventionally delineated in the rat extends ventrally and rostrally beneath the transverse limb of the anterior commissure, invading the olfactory tubercle with its most ventral ramifications. This infracommissural subdivision of the globus pallidus or ventral pallidum (VP) is most selectively identified by being pervaded by a dense plexus of substance-P-positive striatofugal fibers; the extent of this plexus indicates that the VP behind the anterior commissure continues dorsally over some distance into the anteroventromedial part of the generally recognized (supracommissural) globus pallidus; the adjoining anterodorsolateral pallidal region, here named dorsal pallidum (DP), receives only few substance-P-positive fibers, but contains a dense plexus of enkephalin-positive striatal afferents that also pervades VP. Available autoradiographic data indicate that VP and DP receive their striatal innervation from two different subdivisions of the striatum: whereas VP is innervated by a large, anteroventromedial striatal region receiving substantial inputs from a variety of limbic and limbic-system-associated structures (and therefore called "limbic striatum"), DP receives its striatal input from an anterodorsolateral striatal sector receiving only sparse limbic afferents ("nonlimbic" striatum) but instead heavily innervated by the sensorimotor cortex. The present autoradiographic study has produced evidence that this dichotomy in the striatopallidal projection is to a large extent continued beyond the globus pallidus: whereas the efferents of DP were traced to the subthalamic nucleus and substantia nigra, those of VP were found to involve not only the subthalamic nucleus and substantia nigra but also the frontocingulate (and adjoining medial sensorimotor) cortex, the amygdala, lateral habenular and mediodorsal thalamic nucleus, hypothalamus, ventral tegmental area, and tegmental regions farther caudal and dorsal in the midbrain. These findings indicate that the ventral pallidum can convey striatopallidal outflow of limbic antecedents not only into extrapyramidal circuits but also back into the circuitry of the limbic system.

Acetylcholinesterase↗
PubMed1984

Investigation of the reported protective effect of cycloheximide on memory.

Many findings support the hypothesis that formation of long-term memory requires synthesis of proteins in the nervous system close to the time of learning. This hypothesis has been challenged recently by reports that the protein synthesis inhibitor cycloheximide (CYC) injected 2 hr prior to passive avoidance training in mice or rats attenuated the memory impairment induced by a usually amnestic dose of CYC administered 30 min pretraining. To investigate the reports of a "protective" effect of the prior injection, we attempted to replicate them and test their generality. For replication we administered either paired injections of CYC--120 mg/kg 2 hr prior to training and 30 mg/kg 30 min prior to training--or single injections of CYC (either 120 mg/kg or 30 mg/kg) 30 min pretraining and tested for retention of the passive avoidance habit either 1 or 7 days later. No attenuation of amnesia was observed at 1 day tests. Attenuation of amnesia following the double injection of CYC was observed at 7 day tests. When another protein synthesis inhibitor, anisomycin, was used in the same experimental design, there was no "protective" effect; two injections of anisomycin produced greater memory impairment for the passive avoidance habit than did the single low dose. Also, for active avoidance training, two successive injections of CYC caused significantly greater amnesia than did a single dose; this is the opposite of a "protective" effect. We suggest that the reported "protective" effect of CYC on memory is an as yet unexplained phenomenon that does not generalize to other antibiotic drugs and is specific to the passive avoidance task.

Animals↗
PubMedDate not supplied

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Occupational Therapy↗