Biomedical subjects

A J McDonald

Publications and source records attributed to A J McDonald.

At least 19 recordsLinked to original sources

PubMed1997

Calbindin-D28k immunoreactivity in the rat amygdala.

Calbindin-D28k (CB) is a calcium-binding protein whose exact function has yet to be elucidated. Because CB is contained in distinct cell types in the nervous system, it is a valuable marker for distinguishing specific nuclear subdivisions and neuronal populations. In the present study, immunohistochemical methods were used to localize CB in the rat amygdala. A subpopulation of nonpyramidal neurons in all nuclei of the basolateral amygdala (ABL) exhibited intense CB immunoreactivity (CB-ir). CB-positive puncta resembling axon terminals were observed surrounding pyramidal perikarya in the ABL. Pyramidal neurons in caudal and lateral portions of the ABL exhibited moderate CB-ir. Intensely stained nonpyramidal neurons resembling those of the ABL were also seen in the cortical nuclei, periamygdaloid cortex, and nucleus of the lateral olfactory tract; these nuclei also contained variable numbers of moderately stained pyramidal cells. Numerous CB-positive neurons were observed in all subdivisions of the medial nucleus. The posterodorsal subdivision of the medial nucleus exhibited a centrally located island of small CB-negative neurons and three cell-dense clusters of CB-positive neurons. The distribution of CB-ir in the central nuclear complex was very heterogeneous. The intermediate subdivision of the central nuclear complex exhibited the most robust staining, whereas the lateral subdivision contained relatively few CB-positive cells. Dorsal and ventral portions of the lateral capsular subdivision of the central nuclear complex could be readily distinguished on the basis of differing levels of CB-ir. These results indicate that CB is localized in discrete cell types and nuclear subdivisions in the rat amygdala and suggest that CB immunohistochemistry is a useful technique for identifying specific structural components in this brain region.

Amygdala↗

PubMed1996

Localization of AMPA glutamate receptor subunits in subpopulations of non-pyramidal neurons in the rat basolateral amygdala.

A two-color immunoperoxidase technique was used to investigate the localization of GluR1 and GluR2/3 alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) glutamate receptor subunits in subpopulations of non-pyramidal neurons in the rat basolateral amygdala. Antibodies to neuropeptide Y (NPY), vasoactive intestinal peptide (VIP), and calcium binding proteins were used to mark three distinct subsets of non-pyramidal cells. Only non-pyramidal neurons containing the calcium binding proteins parvalbumin (PV) and calbindin D-28k (CB) exhibited robust GluR1-like immunoreactivity (GluR1-ir). Light GluR1-ir was observed in some neurons with NPY-ir and VIP-ir, as well as in some pyramidal cells. Only pyramidal cells exhibited robust GluR2/3-ir. No significant amount of GluR2/3-ir was seen in any of the three main classes of non-pyramidal cells. These findings indicate that in the rat basolateral amygdala GluR2/3-ir is found primarily in pyramidal neurons whereas GluR1-ir is found mainly in non-pyramidal neurons that contain PV or CB.

Amygdala↗

PubMed1996

Immunohistochemical localization of the beta 2 and beta 3 subunits of the GABAA receptor in the basolateral amygdala of the rat and monkey.

The basolateral amygdala has a strong intrinsic inhibitory system mediated by GABAA receptors and is the main site of the anxiolytic actions of benzodiazepines. In an effort to identify the anatomical substrates for these transmitter and drug actions, immunohistochemical techniques were used to analyse the neuronal localization of the beta 2 and beta 3 receptor subunits of the GABAA-benzodiazepine receptor complex in the rat and monkey basolateral amygdala. The overall pattern of GABAA-benzodiazepine receptor immunoreactivity was very similar in both species. The density of the immunoreactivity in the neuropil varied in different nuclei of the basolateral amygdaloid complex. In both species the neuropil of the lateral nucleus exhibited the most robust staining. Immunoreactivity was also seen in neuronal perikarya and dendrites where it was localized to the cytoplasm and/or surface membrane. The cell type with the strongest immunoreactivity was a subpopulation of small non-pyramidal neurons that had numerous thin dendrites. Other larger non-pyramidal neurons were also stained. Pyramidal neurons in the rat and monkey basolateral amygdala exhibited light to moderate perikaryal staining that varied in different nuclei. The results of this study indicate that the pattern of GABAA-benzodiazepine receptor immunoreactivity in the neuropil of the rat and monkey basolateral amygdala closely resembled the distribution of benzodiazepine receptors localized in previous radioligand autoradiographic studies. The finding of intense immunoreactivity in subpopulations of non-pyramidal neurons suggests the existence of disinhibitory mechanisms which may be important for the activation of basolateral amygdaloid projection neurons.

Amygdala↗

PubMed1995

Synaptology of prefrontal cortical projections to the basolateral amygdala: an electron microscopic study in the rat.

Prefrontal projections to the magnocellular basal amygdaloid nucleus (Bmg) of the rat were investigated using Phaseolus vulgaris leucoagglutinin (PHA-L) as an anterograde tracer. Electron microscopic examination revealed that most axon terminals in Bmg labeled by PHA-L injections into the prelimbic area contained round synaptic vesicles and made asymmetric synapses. The great majority of labeled terminals (93%) made synaptic contact with dendritic spines; a few contacts (7%) were seen with thin dendrites. These findings indicate that the main postsynaptic targets of PFC afferents to Bmg are spiny pyramidal neurons, the projection neurons of the basolateral amygdala. The morphology of the synapses suggests that they are excitatory.

Amygdala↗

PubMed1995

Neuropeptide Y and somatostatin-like immunoreactivity in neurons of the monkey amygdala.

Neurons in the monkey amygdala exhibiting neuropeptide Y-like immunoreactivity and somatostatin-like immunoreactivity were identified using an avidin-biotin immunohistochemical technique. Differential co-existence of the two peptides was demonstrated using two-color immunoperoxidase and adjacent section methods. Numerous neuropeptide Y-positive neurons were observed in the basolateral and superficial amygdaloid nuclei. A moderate number of neuropeptide Y-positive neurons was seen in the medial subdivision of the central nucleus, but only a few neurons were observed in the lateral subdivision. Numerous somatostatin-positive neurons were stained in all major amygdaloid nuclei and always outnumbered neuropeptide Y-positive cells. All amygdaloid nuclei contained numerous peptide-positive fibers whose density varied depending on the nucleus. Approximately 90% of neuropeptide Y-positive neurons also exhibited somatostatin-like immunoreactivity. The percentage of somatostatin-positive neurons that exhibited neuropeptide-Y immunoreactivity varied in different nuclei. In the superficial amygdaloid nuclei, medial subdivision of the central nucleus and most portions of the basolateral nuclei the predominant cell type stained with both the neuropeptide Y and somatostatin antibodies was a spine-sparse non-pyramidal neuron. In the dorsal portion of the lateral nucleus, however, most peptide-positive neurons had spiny dendrites. Only the cell bodies and proximal dendrites of somatostatin-positive neurons in the lateral subdivision of the central nucleus were immunostained. This study demonstrates that specific cell populations in the primate amygdala contain neuropeptide Y, somatostatin or both peptides. Most peptide-positive neurons in the basolateral and superficial amygdaloid nuclei appear to be local circuit neurons that contribute to the dense plexus of peptide-positive axons in these regions. The finding of neurons with spiny dendrites in the dorsal part of the lateral nucleus suggests that these cells may be functionally different from peptide-positive neurons in other portions of the basolateral amygdala. The lateral subdivision of the central nucleus is distinguished from other amygdaloid nuclei by containing a large population of somatostatin-positive neurons that do not exhibit neuropeptide Y immunoreactivity.

Amygdala↗

PubMed1994

Neuronal localization of glutamate receptor subunits in the basolateral amygdala.

Antibodies to the NMDAR1 glutamate receptor subunit and the GluR1 and GluR2/3 subunits of the AMPA glutamate receptor were used to localize these receptor components in the basolateral amygdala (ABL) of the rat and monkey. A similar localization pattern was observed in both species. Pyramidal neurons exhibited high levels of NMDAR1 and GluR2/3 immunoreactivity (ir), but low levels of GluR1-ir. Some non-pyramidal cells exhibited high levels of NMDAR1-ir or GluR1-ir, but none exhibited significant levels of GluR2/3-ir. This differential localization of receptor subunits suggests that glutamate receptors will exhibit specific functional properties in distinct subpopulations of ABL neurons.

Amygdala↗

PubMed1994

Calretinin immunoreactive neurons in the basolateral amygdala of the rat and monkey.

The calcium-binding protein calretinin was localized in the basolateral amygdala (BLA) of the rat and monkey using immunohistochemical techniques. In both species the predominant cell type exhibiting calretinin-like immunoreactivity (CR-ir) was a small non-pyramidal neuron with a bipolar or bitufted dendritic arborization pattern. Some pyramidal neurons also exhibited light CR-ir. In the monkey there was an additional population of large moderately-stained neurons with well-stained dendrites. These results indicate that calretinin is found in specific cell types in BLA. The small non-pyramidal CR-ir neurons are morphologically similar to BLA neurons that exhibit immunoreactivity for vasoactive intestinal polypeptide (VIP). These CR-ir neurons in BLA closely resemble the small bipolar CR-ir neurons of the cerebral cortex.

Amygdala↗

PubMed1994

A sexually dimorphic population of CRF neurons in the medial preoptic area.

The neuropeptide corticotropin-releasing factor (CRF) is thought to mediate the induction of a constellation of behavioral, endocrine, and autonomic responses which are important for an animal's adaptation to stressful events. We have found that the anteroventral periventricular preoptic nucleus (AVPv) and medial preoptic nucleus (MPN) of colchicine-injected female rats contained numerous intensely stained CRF-immunoreactive neurons. The AVPv/MPN in males contained very few CRF-immunoreactive neurons per section, even in colchicine-injected animals. This sexually dimorphic population of CRF-immunoreactive neurons in the AVPv may play some role in the sex-related differences in hormonal responses to stress and/or in the control of female reproductive events.

Animals↗

PubMed1993

Immunocytochemical staining of neuropeptide Y (NPY) in the insular lobe of the monkey: a light microscopic study.

Neuropeptide Y (NPY) has been detected immunocytochemically in cerebral cortex and subcortical white matter of the primate frontal, parietal, temporal, and occipital lobes. Because little is known about NPY in the primate insular lobe and because peptides play an important role in normal neuronal functioning and alterations in brain peptides are associated with certain neurological diseases, we studied the presence, distribution, and structural characteristics of NPY-immunostained elements at the light microscopic level in the insula of Macaca fascicularis. We used free-floating sections, rabbit anti-porcine NPY serum, and the avidin and biotinylated peroxidase complex technique. Neuropeptide Y-immunostained neurons were demonstrated in layers II, III, and V/VI, and in the adjoining subcortical white matter. Immunostaining was localized to neuronal somata, neuronal processes, and a delicate plexus in the neuropil. The majority of NPY-immunostained neurons were non-pyramidal, had round somata 10-20 microns in major transverse diameter, and two or three neuronal processes. Computer-aided quantitative analysis of the length, breadth, and area of NPY-stained neurons was performed. Our findings are consistent with observations by others on the presence, laminar distribution, and structural characteristics of NPY-immunostained elements at the light microscopic level in other cerebral lobes of non-human primates.

Animals↗

PubMed1993

Corticoamygdaloid and corticocortical projections of the rat temporal cortex: a Phaseolus vulgaris leucoagglutinin study.

The projections of the rat temporal cortex to the amygdala and cerebral cortex were studied using the sensitive anterograde tracer, Phaseolus vulgaris leucoagglutinin. These studies revealed that the core of temporal area 1 had no projections to the amygdala but did send efferents to several cortical fields that projected to the amygdala, including temporal area 2, temporal area 3, the lateral occipital area 2, and a cortical zone along the dorsal, rostral and caudal borders of temporal area 1 ("Tel fringe"). The temporal area 1 fringe cortex had light projections to the amygdala that were confined to the dorsolateral subdivision of the lateral amygdaloid nucleus. Temporal area 2 and the caudal portion of temporal area 3 had projections to both the dorsolateral and ventromedial subdivisions of the lateral nucleus; the projection from temporal area 2 targeted mainly the ventromedial subdivision, whereas the projection from the caudal portion of temporal area 3 terminated primarily in the dorsolateral subdivision. The rostral portion of temporal area 3 had projections to both subdivisions of the lateral nucleus and to the basal magnocellular nucleus. Temporal areas 2 and 3 also had light projections to the lateral capsular subdivision of the central amygdaloid nucleus. Temporal cortical areas exhibited extensive reciprocal connections with each other. Temporal areas with amygdaloid projections also had extensive projections to the perirhinal cortex. The results of the present investigation, in conjunction with other studies of temporal cortical connections, suggest that all temporal regions projecting to the amygdala are multimodal sensory areas. The core of temporal area 1, which is probably the primary auditory area, apparently has no direct projections to the amygdala. The differential projections of different temporal areas to the amygdala suggests the existence of several distinct multimodal pathways arranged in a parallel configuration.

Amygdala↗

PubMed1993

Localization of GABA-like immunoreactivity in the monkey amygdala.

Neurons exhibiting GABA-like immunoreactivity were identified in the monkey amygdala using an avidin-biotin immunohistochemical technique. The pattern of GABA immunoreactivity was very similar in the basolateral and superficial amygdaloid nuclei. In these regions GABA-positive cells were nonpyramidal neurons that were often arranged in clusters or curvilinear rows. These GABA-positive nonpyramidal neurons constituted about 25% of the total neuronal population of the basolateral and superficial amygdaloid nuclei. Numerous GABA-positive puncta resembling axon terminals were observed both in the neuropil and encapsulating the perikarya of GABA-negative pyramidal cells. The pattern of GABA-like immunoreactivity was different in the central and medial amygdaloid nuclei. These regions contained a very dense array of GABA-positive puncta. There were numerous GABA-positive neurons in the lateral subdivision of the central nucleus and fewer cells in the medial nucleus and medial subdivision of the central nucleus. Many immunoreactive puncta were observed contacting the perikarya and dendrites of GABA-positive cells in these regions. The intercalated nuclei consisted of numerous, small, GABA-positive neurons and a few, larger, GABA-negative cells. Both cell types were contacted by GABA-positive puncta. This study indicates that neuronal subpopulations in each of the amygdaloid nuclei of the monkey are GABAergic. The pattern of immunoreactivity varies in different amygdaloid regions and is very similar to that described in the rat. Certain aspects of the functional organization of this rich GABAergic circuitry can be elucidated by correlating the findings of the present investigation with previous anatomical, physiological, and pharmacological studies of the amygdala.

Amygdala↗

PubMed1993

Identification of putative nitric oxide producing neurons in the rat amygdala using NADPH-diaphorase histochemistry.

Putative nitric oxide-containing neurons in the rat amygdala were studied using reduced nicotinamide adenine dinucleotide phosphate diaphorase histochemistry. All nuclei of the amygdala contained subpopulations of diaphorase-positive neurons, but the staining intensity of different subpopulations varied. Intensely stained neurons exhibited labeling of the cell body and the entire dendritic arborization. The lateral nucleus had the greatest concentration of intensely labeled cells. Many intensely labeled neurons were located along nuclear boundaries and fiber bundles. In addition to neuronal staining, there was a differential staining of the neuropil in different amygdaloid nuclei. In the basolateral and cortical nuclei the diaphorase-positive cells were non-pyramidal neurons that resembled those containing somatostatin and neuropeptide Y. The distribution and neuronal morphology of labeled neurons in the central nucleus and anterior amygdaloid area suggests that diaphorase-positive cells in these areas may be cholinergic. Recent studies have shown that the enzyme responsible for neuronal diaphorase activity is actually the synthetic enzyme for the newly discovered neurotransmitter nitric oxide. Since there is evidence that nitric oxide plays an important role in excitotoxic neuronal degeneration, the neurons identified in the present study may be involved in degenerative diseases of the amygdala.

Amygdala↗

PubMed1993

Oral labetalol versus oral nifedipine in hypertensive urgencies in the ED.

Therapy in hypertensive urgencies is debated and complicated by the side effects of available agents. In a prospective, randomized, open labeled study, the use of oral labetalol, an alpha- and beta-adrenergic blocker, with oral nifedipine in hypertensive urgencies in the emergency department was compared. Patients with diastolic blood pressures (DBP) of more than 120 mm Hg without criteria for a hypertensive emergency were eligible. The drugs were given in a loading manner with doses and timing based on their respective pharmacokinetics until a DBP of 110 mm Hg or lower was obtained or 4 hours had passed. Either an initial labetalol dose of 200 mg and a repeat dose of 100 to 200 mg at 2 hours, depending on the DBP or nifedipine, 10-mg bite and swallow every hour up to a total dose of 20 mg were given. Ten patients were enrolled into each study group. A 100% response rate was defined as a DBP of 110 mm Hg or less was observed for nifedipine and an 80% response rate for labetalol (P > .2) was observed. The mean time to control was 67.5 minutes for labetalol and 60.0 minutes for nifedipine (P > .2). The pretreatment pressure for labetalol was 195/127 mm Hg and for nifedipine was 198/128 mm Hg (P > .2), which decreased to a posttreatment pressure for labetalol of 154/100 mm Hg and for nifedipine of 163/100 mm Hg (P > .2). The mean decrease in systolic (SBP)/DBP was 42.6/26.5 mm Hg with labetalol and 34.9/28.4 mm Hg for nifedipine (P > .2). No significant side effects occurred with either drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

PubMed1992

The inferior colliculus: calbindin and parvalbumin immunoreactivity in neural grafts.

The inferior colliculus was selected as a brain stem site for study of neural grafting and identification of calcium binding proteins. Unilateral ablation sites of eight midbrain inferior colliculus in adult Long-Evans rats were implanted with E17-18 caudal tectum. After 2 to 9 months animals were sacrificed and sections reacted using antibodies for calbindin and parvalbumin. The central nucleus of normal inferior colliculus shows high density of neuronal and fiber staining for parvalbumin. Typical graft cores had similar staining distributions including discoid and stellate neuron populations. Graft cores showed low densities of reactivity for calbindin comparable to central nucleus. In surrounding graft regions there was substantive-neuronal and fiber labeling for calbindin and parvalbumin including stellate neuron populations normally found in the dorsal and lateral nuclei of inferior colliculus. These results demonstrate that the expression of calcium binding proteins in tectal grafts resembles that of inferior colliculus.

Animals↗

PubMed1992

Projection neurons of the basolateral amygdala: a correlative Golgi and retrograde tract tracing study.

This study analyzed the projection neurons of the anterior subdivision of the rat basolateral amygdaloid nucleus (BLa) by correlating the morphology of Golgi-stained neurons with the morphology of neurons that were retrogradely labeled by injections into the main terminal fields of BLa. In each animal multiple injections of horseradish peroxidase (HRP) and wheat germ agglutinin-conjugated HRP were made into the prefrontal cortex and rostral striatum. These injections labeled approximately 85% of BLa neurons. The great majority of labeled neurons were the same shape and relative size as the pyramidal (class I) neurons described in previous Golgi studies. The unlabeled neurons appeared to correspond to the nonpyramidal (class II and class III) neurons described in Golgi studies. Thus this investigation provides experimental evidence that the pyramidal neurons are the main projection neurons of BL, whereas most of the nonpyramidal cells are local circuit neurons.

Amygdala↗

PubMed1992

Biocytin injections produce selective neuronal labeling in the rat CNS.

Large injections of biocytin into the lateral ventricle or brain resulted in the labeling of particular neuronal subpopulations in the rat CNS. Localization was accomplished using the avidin-biotin-peroxidase technique. In many cases the staining of neurons was totally complete and resembled that obtained with the Golgi technique. Regions containing labeled cells included the olfactory bulb, cerebral cortex, hippocampus, amygdala, striatum, hypothalamus, superior and inferior colliculi, cerebellar cortex, and dorsal horn of the spinal cord. Only particular cell types were labeled in each of these regions. The results of this study suggest that there is selective uptake and/or retention of biocytin, or a biotinylated metabolite of biocytin, by subpopulations of CNS neurons.

Animals↗

PubMed1992

Neuroanatomical labeling with biocytin: a review.

Recent studies have shown that biocytin may have multiple applications in neuroanatomical studies. Biocytin may be injected into the brain by iontophoresis or by pressure injection methods, and localized in tissue sections using avidin-conjugated labels. It is taken up by neurons and rapidly transported down axons in an anterograde fashion. Axons are completely labeled in a Golgi-like manner and can be examined at both light and electron microscopic levels. Biocytin can also be used in retrograde tract tracing experiments, although in some cases it appears that fibers must be damaged to produce such labeling. Retrogradely labeled cells may be completely labeled, resembling neurons stained with the Golgi technique. Individual neurons can also be labeled in a Golgi-like manner by uptake of biocytin from the extracellular space. Thus, it appears that biocytin is an especially versatile marker for neuroanatomical investigations.

Animals↗

PubMed1991

Organization of amygdaloid projections to the prefrontal cortex and associated striatum in the rat.

The organization of connections between the amygdala, prefrontal cortex and striatum was studied using anterograde and retrograde tract tracing techniques in the rat. The anterograde transport of Phaseolus vulgaris leucoagglutinin and wheat germ agglutinin conjugated to horseradish peroxidase was used to examine the striatal projections of the prefrontal cortex. These studies revealed that the prelimbic area of the medial prefrontal cortex projects mainly to the medial part of the striatum, whereas the dorsal agranular insular area of the lateral prefrontal cortex projects mainly to the ventrolateral part of the striatum. The organization of amygdaloid projections to the prefrontal cortex and its associated portions of the striatum was investigated using the fluorescence retrograde tract tracing technique. Different color fluorescent dyes, True Blue and Diamidino Yellow, were injected into the prefrontal cortex and striatum. These studies demonstrated that medial portions of the basolateral nucleus, and adjacent portions of the lateral, basomedial and amygdalo-hippocampal nuclei, project to both the medial prefrontal cortex and its associated medial striatal region. The rostral pole and lateral portions of the basolateral nucleus project to both the lateral prefrontal cortex and its associated lateral striatal region. Many neurons in the basolateral amygdaloid nucleus, and to a lesser extent other amygdaloid nuclei, were double-labeled in these experiments, indicating that these cells send collaterals to both the prefrontal cortex and striatum. These findings indicate that discrete areas of the amygdala, and in some cases individual amygdaloid neurons, can modulate information processing in the first two links of distinct cortico-striato-pallidal systems arising in the medial and lateral prefrontal cortex.

Afferent Pathways↗