Biomedical subjects

G Paxinos

Publications and source records attributed to G Paxinos.

At least 19 recordsLinked to original sources

PubMed2006

Development of the human nucleus of the solitary tract: a cyto- and chemoarchitectural study.

The present study investigated the prenatal development of the cyto- and chemoarchitecture of the human nucleus of the solitary tract from 9 to 35 weeks, by using Nissl staining and immunoreactivity to calbindin, calretinin, tyrosine hydroxylase and GAP-43. The nucleus began to gain heterogeneity and show different subnuclei as early as 13 weeks, and approached cytoarchitectural maturation from 21 to 25 weeks. The subnuclear division pattern observed in the fetal nucleus of the solitary tract at 25 weeks was very similar to that of the adult. Neurons immunoreactive to calbindin first appeared in the medial gastrointestinal area of the nucleus at 13 weeks, particularly within a putative gelatinosus subnucleus, while calretinin immunoreactivity during fetal life suggested the possible presence of a central subnucleus. Tyrosine hydroxylase immunoreactive neurons were seen in the medial subdivisions of the nucleus of the solitary tract as early as 13 weeks, but the population continued to increase until 25 weeks. Strong GAP-43 immunoreactivity was also present in the nucleus of the solitary tract at 13 weeks, especially in the dorsolateral and commissural subnuclei, while at 21 weeks there was a significant decline of GAP-43 expression. Results from the chemoarchitectural study showed that the human nucleus of the solitary tract expressed various neurochemical substances at an early developmental age (13 weeks), even before cellular and neuropil maturation was fully attained. Expression of these factors may play an important role in establishment and integration of viscerosensory function in the nucleus.

Aborted Fetus↗

PubMed2004

Central vagal sensory and motor connections: human embryonic and fetal development.

The embryonic and fetal development of the nuclear components and pathways of vagal sensorimotor circuits in the human has been studied using Nissl staining and carbocyanine dye tracing techniques. Eight fetal brains ranging from 8 to 28 weeks of development had DiI (1,1'-dioctadecyl-3,3,3',3' tetramethylindocarbocyanine perchlorate) inserted into either the thoracic vagus nerve at the level of the sternal angle (two specimens of 8 and 9 weeks of gestation) or into vagal rootlets at the surface of the medulla (at all other ages), while a further five were used for study of cytoarchitectural development. The first central labeling resulting from peripheral application of DiI to the thoracic vagus nerve was seen at 8 weeks. By 9 weeks, labeled bipolar cells at the ventricular surface around the sulcus limitans (sl) were seen after DiI application to the thoracic vagus nerve. Subnuclear organization as revealed by both Nissl staining and carbocyanine dye tracing was found to be advanced at a relatively early fetal age, with afferent segregation in the medial Sol apparent at 13 weeks and subnuclear organization of efferent magnocellular divisions of dorsal motor nucleus of vagus nerve noticeable at the same stage. The results of the present study also confirm that vagal afferents are distributed to the dorsomedial subnuclei of the human nucleus of the solitary tract, with particular concentrations of afferent axons in the gelatinosus subnucleus. These vagal afferents appeared to have a restricted zone of termination from quite early in development (13 weeks) suggesting that there is no initial exuberance in the termination field of vagal afferents in the developing human nucleus of the solitary tract. On the other hand, the first suggestion of afferents invading 10N from the medial Sol was not seen until 20 weeks and was not well developed until 24 weeks, suggesting that direct monosynaptic connections between the sensory and effector components of the vagal sensorimotor complex do not develop until this age.

Carbocyanines↗

PubMed2004

In vitro autoradiographic localization of calcitonin and amylin binding sites in monkey brain.

Calcitonin (CT) and amylin are related peptides with potent central actions, including suppression of appetite and gastric acid secretion. Little is known about the distribution and binding characteristics of amylin receptors in species other than rat; therefore, in this study, by using in vitro autoradiography, we have mapped the distribution of 125I-rat amylin binding sites in the monkey brain and compared this distribution to that of binding sites for 125I-salmon CT (125I-sCT). Highest densities of 125I-amylin binding were in the hypothalamus, including the arcuate nucleus and parts of the ventromedial hypothalamic nuclei, and the solitary nucleus. Rostrally, moderate to high density binding was present in parts of the preoptic area, bed nucleus of the stria terminalis, amygdala and accumbens nucleus (Acb). Caudally, binding of amylin was more restricted, with moderate to high density binding present only in dorsal raphe, and area postrema. The primary visual cortex displayed strong and periodic CT binding in layer 4. The subcortical pattern of distribution of amylin and CT receptors in the monkey was similar to that seen previously in the rat, although the relative densities of binding to different brain structures were not always conserved. As with rat, monkey amylin receptors were a subset of the sites labeled with 125I-sCT. Analysis of receptor specificity indicated a greater relative potency of CT peptides in competing for 125I-amylin binding in monkey, when compared to rat, while, there was a decrease in the relative potency of CT gene-related peptides, potentially due to differences the level of receptor activity modifying proteins (RAMPs) in monkey versus rat brain. Amylin receptors in primates are likely to perform a similar role to those in rats; however, the interaction of the receptors with related peptides may differ.

Amyloid↗

PubMed2003

The anatomy of the cerebral cortex of the echidna (Tachyglossus aculeatus).

The cerebral cortex of the echidna is notable for its extensive folding and the positioning of major functional areas towards its caudal extremity. The gyrification of the echidna cortex is comparable in magnitude to prosimians and cortical thickness and neuronal density are similar to that seen in rodents and carnivores. On the other hand, many pyramidal neurons in the cerebral cortex of the echidna are atypical with inverted somata and short or branching apical dendrites. All other broad classes of neurons noted in therian cortex are also present in the echidna, suggesting that the major classes of cortical neurons evolved prior to the divergence of proto- and eutherian lineages. Dendritic spine density on dendrites of echidna pyramidal neurons in somatosensory cortex and apical dendrites of motor cortex pyramidal neurons is lower than that found in eutheria. On the other hand, synaptic morphology, density and distribution in somatosensory cortex are similar to that in eutheria. In summary, although the echidna cerebral cortex displays some structural features, which may limit its functional capacities (e.g. lower spine density on pyramidal neurons), in most structural parameters (e.g. gyrification, cortical area and thickness, neuronal density and types, synaptic morphology and density), it is comparable to eutheria.

Animals↗

PubMed2000

The distribution of the neurokinin B receptor in the human and rat hypothalamus.

The neurokinin B receptor (NK3) is an element of the hypothalamic neuronal circuitry regulating blood pressure in rats. The present study used immunohistochemistry to reveal the distribution of NK3 in the human hypothalamus. The strongest NK3-like immunoreactivity in the human hypothalamus was found in neurons of the paraventricular nucleus, specifically in the parvicellular and posterior paraventricular subnuclei. Another prominent population of NK3-positive cells in the human hypothalamus was found in the perifornical nucleus. The present study also showed two previously unreported populations of NK3-positive neurons in the rat periventricular nucleus and medial magnocellular paraventricular subnucleus. It is concluded that there is a large degree of similarity in the distribution of NK3 in the human and rat hypothalamus.

Adult↗

PubMed2000

Organization of the human paraventricular hypothalamic nucleus.

The cyto- and chemoarchitecture of the human paraventricular hypothalamic nucleus (Pa) was studied with the aid of three-dimensional computer reconstruction. The adult human Pa is a vertically elongated structure that abuts the wall of the third ventricle (3V) medially and is indented dorsolaterally by the descending fornix. Chemoarchitecture revealed the following five subnuclei in the human Pa. The most prominent of these is the magnocellular subnucleus (PaM) occupying the ventrolateral quadrant of the Pa and comprised of a concentration of large arginin-vasopressin (AVP)- and acetylcholinesterase (AChE)-positive cells, and small calbindin (Cb)-positive neurons. Rostrally, the PaM is succeeded by the small anterior parvicellular subnucleus (PaAP), which contains small AChE-, AVP- and tyrosin hydroxylase (TH)-positive cells. Dorsal to the PaM is found the dorsal subnucleus (PaD), containing large spindle-shaped TH-, oxytocin (OXY)-, and AChE-positive cells, as well as a population of small Cb-positive neurons. Abutting the wall of the 3V and medial to PaM and PaD is the parvicellular subnucleus (PaP). The PaP contains small cells immunoreactive for corticotropin-releasing factor (CRF), neuromedin K receptor (NK3), and nonphosphorylated neurofilament protein (SMI32). The posterior subnucleus (PaPo) is situated posterior to the descending column of the fornix; it replaces all above-mentioned subdivisions caudally, and is a chemoarchitectonic amalgam that includes dispersed large AChE-, OXY-, AVP- and TH-positive cells, as well as small NK3-, CRF-, SMI32- and Cb-immunoreactive neurons. The present findings suggest that the human PaM and PaD are homologues to the magnocellular subnuclei of the rat Pa, whereas the human PaP and PaPo correspond to the rat medial parvicellular and posterior subnuclei, respectively.

Acetylcholinesterase↗

PubMed2000

Architectonic analysis of the human retrosplenial cortex.

The architecture of the macaque retrosplenial cortex, including its posteroventral extension around and below the splenium of the corpus callosum, was recently characterized (Morris et al. [1999a] Eur. J. Neurosci. 11:2506-2518.). This analysis was made possible by sectioning the posterior cingulate gyrus radially, i.e., in planes that were orthogonal to its line of curvature and that, therefore, preserved the laminar organization of this region. The aim of the present study was to examine the architecture and the limits of the human retrosplenial cortex. Cross sections through the entire posterior cingulate gyrus were obtained by applying the sectioning technique developed in the monkey, so that an explicit comparison could be made between the architecture of the human and the monkey retrosplenial cortex. The present analysis revealed that, as is the case in the macaque brain, the human retrosplenial cortex is composed of granular areas 29a-c and d, and dysgranular/agranular area 30. The human retrosplenial cortex, like that of the macaque monkey, runs, as an arch, around the splenium of the corpus callosum. In the macaque brain, the retrosplenial cortex remains buried within the callosal sulcus throughout its entire course around the splenium. In the human brain, however, the posteroventral segment of the retrosplenial cortex extends on the medial wall of the cerebral hemisphere to encompass most of the cortical region commonly referred to as the "isthmus of the cingulate gyrus."

Adult↗

PubMed2000

Conditioned changes in ultrasonic vocalizations to an aversive olfactory stimulus are lateralized in 6-day-old rats.

Using a soft rubber plug to block airflow in one naris, Kucharski, Johanson, and Hall (1986) found that some forms of olfactory memory (e.g., odor preferences) were lateralized in young rats while other forms (e.g., conditioned activation and mouthing) were not. The present experiments extended that research by showing that conditioned increases in ultrasonic vocalizations were also lateralized. That is, when exposed to an odor that was previously paired with footshock, 6-day-old rats significantly increased their rate of vocalizing. This response only occurred, however, when the naris open at training was also open at test. The use of the developing rat as a natural split-brain preparation appears to be an effective procedure with which to broaden current approaches to the analysis of learning, memory, and emotion.

Age Factors↗

PubMed2000

Distribution of angiotensin IV binding sites (AT4 receptor) in the human forebrain, midbrain and pons as visualised by in vitro receptor autoradiography.

Angiotensin IV and other AT4 receptor agonists, improve memory retention and retrieval in the passive avoidance and swim maze learning paradigms. Angiotensin IV binding sites (also known as the AT4 receptors) are widely distributed in guinea pig and monkey (Macaca fascicularis) brains where high densities of the binding sites have been detected in the hippocampus, neocortex and motor nuclei. However, the distribution of the binding sites in the human brain is not known. We have recently localised the angiotensin IV binding sites (AT4 receptors) in post-mortem human brain using iodinated Nle-angiotensin IV, a higher affinity and more stable analogue of angiotensin IV. This radioligand bound with relatively high affinity and specificity to angiotensin IV binding sites. In competition studies on consecutive sections through the prefrontal cortex and claustrum, angiotensin IV, Nle-angiotensin IV and LVV-hemorphin 7 competed for the binding of 125I[Nle]-angiotensin IV with nanomolar affinities. Angiotensin II and the AT1 and AT2 receptor antagonists were ineffective in competing for the binding at concentrations of up to 10 microM. We found high densities of 125I[Nle]-angiotensin IV binding sites throughout the cerebral cortex including the insular, entorhinal, prefrontal and cingulate cortices. Very high densities of the binding sites were observed in the claustrum, choroid plexus, hippocampus and pontine nucleus. Some thalamic nuclei displayed high densities of binding including the anteroprincipal, ventroanterior, anteromedial, medial dorsal and ventrolateral nuclei. The caudate nucleus, putamen, many amygdaloid nuclei and the red nucleus all displayed moderate densities of binding with a higher level detected in the substantia nigra pars compacta. In the hypothalamus, high densities binding sites were found in the ventromedial nucleus with lower levels in the dorsomedial and paraventricular nuclei. The distribution of 125I[Nle]-angiotensin IV binding sites in the human brain is similar to that found in other species and supports multiple roles for the binding sites in the central nervous system, including facilitation of memory retention and retrieval.

Aged↗

PubMed2000

Selective right parietal lobe activation during mental rotation: a parametric PET study.

Regional cerebral blood flow (rCBF) was measured with PET in seven healthy subjects while they carried out a mental rotation task in which they decided whether alphanumeric characters presented in different orientations were in their canonical form or mirror-reversed. Consistent with previous findings, subjects took proportionally longer to respond as characters were rotated further from the upright, indicating that they were mentally rotating the characters to the upright position before making a decision. We used a parametric design in which we varied the mental rotation demands in an incremental fashion while keeping all other aspects of the task constant. In four different scanning conditions, 10, 40, 70 or 100% of the stimuli presented during the scan required mental rotation while the rest were upright. The statistical parametric mapping technique was used to identify areas where changes in rCBF were correlated with the rotational demands of the task. Significant activation was found in only one area located in the right posterior parietal lobe, centred on the intraparietal sulcus (Brodmann area 7). The experimental literature on monkeys and humans suggests that this area is involved in a variety of spatial transformations. Our results contribute evidence that such transformations are recruited during mental rotation and add to a body of evidence which suggests that the right posterior parietal lobe is important for carrying out visuospatial transformations.

Adult↗

PubMed2000

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing.

Aging↗

PubMed1998

EphA4 (Sek1) receptor tyrosine kinase is required for the development of the corticospinal tract.

Members of the Eph family of tyrosine kinase receptors have been implicated in the regulation of developmental processes and, in particular, axon guidance in the developing nervous system. The function of the EphA4 (Sek1) receptor was explored through creation of a null mutant mouse. Mice with a null mutation in the EphA4 gene are viable and fertile but have a gross motor dysfunction, which is evidenced by a loss of coordination of limb movement and a resultant hopping, kangaroo-like gait. Consistent with the observed phenotype, anatomical studies and anterograde tracing experiments reveal major disruptions of the corticospinal tract within the medulla and spinal cord in the null mutant animals. These results demonstrate a critical role for EphA4 in establishing the corticospinal projection.

Animals↗

PubMed1998

Regional distribution of low affinity kainate receptors in brain of Macaca fascicularis determined by autoradiography using [3H](2S,4R)-4-methylglutamate.

Binding of [3H](2S,4R)-4-methylglutamate, a novel low affinity kainate receptor agonist, was studied in brain sections of a Macaca fascicularis monkey. In cerebellar sections, [3H](2S,4R)-4-methylglutamate bound to a single population of sites (KD = 20 nM) and was inhibited by various glutamate receptor ligands: kainate > 6-cyano-7-nitroquinoxaline-2,3-dione > L-glutamate >> AMPA. (S)-5-lodowillardiine and (RS)-2-amino-3-(3-hydroxy-5-tert-butylisoxazol-4-yl)propanoic acid (ATPA), drugs selective for the GluR5 subunit, displaced 50% and 40% of binding, respectively. Autoradiography revealed topographic binding of [3H](2S,4R)-4-methylglutamate. Binding in cortex was highest in layer 5 and restricted to CA2/3 in hippocampus. Levels of binding were high in septum and hypothalamus. Moderate densities of binding were found in caudate-putamen, cerebellar granular layer, nucleus tractus solitarius, cuneate nucleus and area postrema. Binding in spinal cord was concentrated in dorsal horn. [3H](2S,4R)-4-Methylglutamate shows differential binding throughout primate brain and is a valuable new ligand for low affinity kainate receptors.

Animals↗

PubMed1998

Autoradiographic localisation of substance P (NK1) receptors in human primary visual cortex.

This study utilised autoradiography to examine [125I]-Bolton Hunter substance P (BHSP) binding in postmortem human visual cortex. In the primary visual area, layers I-III, IVC and VI exhibited low levels of BHSP binding, while high levels were observed in layers IVB and V. Because cells in layers IVB and V are known to be involved in processing direction-specific stimuli, it is possible that SP plays a role in modulating this visual process.

Adult↗

PubMed1998

Long-term effect of VVI pacing on atrial and ventricular function in patients with sick sinus syndrome.

We conducted a prospective, 6-month echocardiographic study on the effect of VVI pacing on left atrial and ventricular function and dimensions in patients with sick sinus syndrome. Thirty-nine patients (23 women and 16 men, aged 71 +/- 9.2 years; 30 in sinus rhythm and 9 in atrial fibrillation) who had a VVI pacemaker implanted because of sick sinus syndrome were recruited in the study. In 26 patients who presented with and remained in sinus rhythm, paced left ventricular ejection fraction and stroke volume were significantly decreased (71.4% +/- 11.8% to 67.0% +/- 13.6%, and 73.9 +/- 29.0 cm3 to 66.3 +/- 21.1 cm3, respectively, P < 0.001 for both), whereas the paced diastolic dimension of the left atrium was significantly increased (3.2 +/- 0.7 cm to 3.7 +/- 0.9 cm, P < 0.001) at 6 months as compared with preimplantation. In nine patients with atrial fibrillation at implantation paced left ventricular ejection fraction at follow-up was significantly decreased (67.7% +/- 10.1% to 64.2% +/- 10.6%, P =0.003), but paced stroke volume and left atrial diastolic dimension were not significantly changed (75.1 +/- 25.6 cm3 to 79.0 +/- 22.7 cm3, and 4.3 +/- 1.2 cm to 4.6 +/- 1.5 cm, P = NS for both) at follow-up. Cessation of pacing and restoration of sinus rhythm in 21 patients at follow-up did not result in any significant change of ejection fraction (67.5% +/- 10.2% ti 67.6% +/- 9.7%, P = NS) whereas stroke volume was increased (59.1 +/- 19.6 cm3 to 69.1 +/- 22.3 cm3, P < 0.0001) in comparison with paced values. However, compared with preimplantation values, ejection fraction was significantly decreased (70.4% +/- 10.0% to 67.6% +/- 9.7%, P = 0.001), whereas stroke volume was not significantly changed (68.4 +/- 22.3 cm3 to 69.1 +/- 22.3 cm3, P = NS) during sinus rhythm at follow-up. In 14 of those patients, discontinuation of pacing resulted in a significant increase of left atrial fractional shortening (8.1% +/- 1.7% to 20.1% +/- 4.3%, P < 0.001) and significant increase of left atrial diastolic dimension compared with paced and preimplantation levels (3.8 +/- 0.7 cm vs 3.6 +/- 0.7 cm and 3.0 +/- 0.5 cm, respectively, P < 0.001). Long-term VVI pacing in patients with sick sinus syndrome results in increase of the left ventricular end-systolic dimension and permanent reduction of the left ventricular ejection fraction. In the left atrium, VVI pacing causes an immediate reduction of the fractional shortening as well as long-term increase of the diastolic dimension.

Aged↗

PubMed1997

Distribution of bradykinin B2 receptors in sheep brain and spinal cord visualized by in vitro autoradiography.

Bradykinin B2 receptors were localized in the sheep brain and spinal cord by quantitative in vitro autoradiography using a radiolabelled and specific bradykinin B2 receptor antagonist analogue, 3-4-hydroxyphenyl-propionyl-D-Arg0-[Hyp3,Thi5,D-Tic 7,Oic8]bradykinin, (HPP-HOE 140). This radioligand displays high affinity and specificity for bradykinin B2 receptors. The respective K(i) values of 0.32, 1.37 and 156 nM were obtained for bradykinin, HOE140 and D-Arg[Hyp3,D-Phe7,Leu8]bradykinin competing for radioligand binding to lamina II of sheep spinal cord sections. Using this radioligand, we have demonstrated the distribution of bradykinin B2 receptors in many brain regions which have not been previously reported. The highest density of bradykinin B2 receptors occur in the pleoglial periaqueductal gray, oculomotor and trochlear nuclei and the circumventricular organs. Moderate densities of receptors occur in the substantia nigra, particularly the reticular part, the posterior thalamic and subthalamic nuclei, zona incerta, the red and pontine nuclei, some of the pretectal nuclei and in discrete layers of the superior colliculus. In the hindbrain, moderate levels of bradykinin B2 receptor binding occur in the nucleus of the solitary tract, and in spinal trigeminal, inferior olivary, cuneate and vestibular nuclei. Laminae II, X and dorsal root ganglia display the most striking binding densities in the spinal cord, while the remainder of the dorsal and ventral horn display a low and diffuse density of binding. Bradykinin B2 receptors are extensively distributed throughout the sheep brain and spinal cord, not only to sensory areas but also to areas involved in motor activity.

Animals↗

PubMed1997

Fos-like immunoreactivity in locus coeruleus after classical conditioning of the rabbit's nictitating membrane response.

We investigated the changes in Fos-like immunoreactivity in the locus coeruleus (LC) after classical conditioning of the rabbit's nictitating membrane. Specifically, we compared unpaired versus paired presentations of a tone conditioned stimulus (CS) and a tactile unconditioned stimulus (US; near the eye). After two training sessions, only paired presentations resulted in acquisition of a conditioned response. This was associated with comparatively less LC Fos expression than with unpaired presentations. Similar observations have been reported for the ventrolateral medulla which is a major source of afferents to LC. The present results are consistent with a role of LC in attention and learning: activity increases as the animal attends to the CS and US. When the relationship between CS and US has been established, LC activity decreases.

Animals↗

PubMed1997

Conditioned fear to context is associated with increased Fos expression in the caudal ventrolateral region of the midbrain periaqueductal gray.

Immunohistochemical detection of Fos was used to determine which regions of the periaqueductal gray are activated during conditioned fear to a context in the rat. More specifically, the aim of the study was to test the role of its lateral and ventrolateral columns in freezing behaviour during fear. Conditioned fear was evoked by re-exposing rats to the same footshock chamber in which they had received footshocks 4 h earlier. Conditioned Re-exposed rats were compared to Not Conditioned Re-exposed and Conditioned Not Re-exposed rats. Freezing was observed in the Conditioned-Re-exposed group only. It was associated with an overall increase in Fos expression in the entire periaqueductal gray that was significantly greater than in the two other groups. The largest and most significant increase in Fos immunoreactivity was found in the ventrolateral column (especially in its caudal part), whereas only a moderate increase was found in the lateral column. The present results argue in favour of the ventrolateral column as the region of the periaqueductal gray that is preferentially involved in expression of conditioned fear. As previous lesion studies suggested, the ventrolateral periaqueductal gray may play a role in mediating the immobility component of freezing induced by fear. Other lines of evidence suggest that it may also play a role in mediating the quiescence immobility associated with deep pain. We propose that the ventrolateral column of the periaqueductal gray acts as an integrating centre mediating behavioural inhibition.

Animals↗