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S L Erickson

Publications and source records attributed to S L Erickson.

13 recordsLinked to original sources

Dopamine innervation of the monkey mediodorsal thalamus: Location of projection neurons and ultrastructural characteristics of axon terminals.

Dopamine (DA) axons and receptors have recently been identified in the primate thalamus, including the mediodorsal thalamic nucleus (MD). In order to determine whether the DA innervation of the primate MD shares the anatomical features of the mesocortical or nigrostriatal DA projections, we performed tract-tracing and immunocytochemistry studies in macaque monkeys (Macaca fascicularis) to identify the location of the DA neurons that project to MD and immuno-electron microscopy to determine the distribution of the dopamine transporter (DAT) in axons within the MD. Similar to the mesocortical projection, retrogradely-labeled, tyrosine hydroxylase-containing neurons were present in dorsal tier ventral mesencephalic nuclei, such as the ventral tegmental area and the dorsal portion of the substantia nigra pars compacta. In contrast, no dual-labeled neurons were present in the ventral tier nuclei, the primary origin of the nigrostriatal DA pathway. In addition, like the DA projection to the prefrontal cortex, DAT immunoreactivity was predominantly localized to the pre-terminal portion of axons in the MD, and was infrequently found in association with synaptic vesicles, in contrast to nigrostriatal DA axons. These findings indicate that the DA projection to the MD shares anatomical features with the mesocortical DA system, suggesting that the functional properties of DA neurotransmission in the MD might be more similar to those in the cortex than in the striatum.

Animals↗

Subcortical afferents to the lateral mediodorsal thalamus in cynomolgus monkeys.

The mediodorsal (MD) nucleus of the thalamus has long been known to provide the principal source of subcortical input to the primate prefrontal cortex, as well as to other areas of the frontal lobe that are thought to contribute to higher-order cognitive functions. In this study, we used injections of retrograde tracers in the lateral portion of the monkey MD to assess the locations of labeled cells in subcortical structures. Three main patterns were identified in the distribution of subcortical connections. We found that the claustrum, superior colliculus and ventral midbrain regions were heavily labeled in the cases with injections in caudoventral MD. In these cases, labeled cells were also found in either the periaqueductal gray or zona incerta, depending on the specific case. In one case with an injection in anterodorsal MD, labeled cells were most numerous in the structures of the ventral midbrain, especially the ventral tegmental area. Finally, the claustrum and superior colliculus contained the largest percentage of labeled subcortical cells in cases with injections in ventrolateral MD. These three patterns of subcortical label corresponded to three equally distinctive trends in the distribution of MD connections with the cortex in these same cases [J Comp Neurol 473 (2004) 107]. Very few labeled cells were found in other areas such as the amygdala, globus pallidus and deep cerebellar nuclei, suggesting that pathways leading from these structures to dorsolateral and dorsomedial frontal cortices are not likely to include the lateral divisions of MD. In concert, these findings show that particular locales within lateral MD receive distinct profiles of subcortical afferents, and project into specific neocortical domains, suggesting that these different sites within lateral MD may participate in functionally distinct circuits of information processing.

Afferent Pathways↗

Effects of in vivo heregulin beta1 treatment in wild-type and ErbB gene-targeted mice depend on receptor levels and pregnancy.

Mice heterozygous (+/-) for either heregulin (HRG), ErbB2, or ErbB3 were created by gene targeting, resulting in the loss of one functional gene copy and an associated decrease in targeted protein. We examined the in vivo activity of recombinant HRG peptide, rHRG beta1 (amino acids 177 to 241), in the three heterozygous mouse lines and in wild-type (WT) mice, both pregnant and nonpregnant. Nonpregnant WT and HRG(+/-) mice of both sexes were sensitive to rHRG beta1 treatment as evidenced by a high mortality rate associated with abdominal enlargement and parietal cell loss. However, pregnant WT mice and ErbB2 and ErbB3 heterozygous mice treated with rHRG beta1 were less affected, with significantly lower mortality rates and a less severe abdominal phenotype. Histological analysis revealed extensive breast ductal hyperplasia in females of all genotypes after rHRG beta1 treatment. Hyperplasia of other epithelial tissues such as the pancreas and intestine and the growth of cardiac nerve bundles were also observed, independent of sex.

Animals↗

Dopamine innervation of monkey entorhinal cortex: postsynaptic targets of tyrosine hydroxylase-immunoreactive terminals.

Dopamine (DA) has been demonstrated to play an important role in regulating cortical activity in both neocortical and periallocortical regions. However, marked differences between these two types of cortices in the laminar pattern of DA axons, the types and distribution of DA receptors, and the postnatal development of the DA innervation suggest that DA may have region-specific effects. Such regional specialization may also include the types of cortical cells apposed to DA terminals. In neocortical regions, such as the prefrontal and motor cortices, the majority of structures apposed to DA terminals appear to be the dendritic spines and shafts of pyramidal cells, and a minority are dendrites immunoreactive for gamma-amino butyric acid (GABA). However, the identity of the neural elements apposed to DA terminals in the entorhinal cortex, a periallocortical region, is unknown. In this study, we used immunocytochemical techniques and antibodies against tyrosine hydroxylase (TH) and GABA, visualized with preembedding immunoperoxidase and immunogold-silver labels, respectively, to examine DA terminals and their targets with electron microscopy. In the superficial layers of the monkey entorhinal cortex, TH-immunoreactive (IR) terminals varied greatly in size and formed thin, symmetric synapses. The majority of dendritic structures apposed to these TH-terminals were not GABA-IR, and included both dendritic shafts (64%) and spines (14%). A minority (22%) of the apposed dendrites were GABA-IR. A similar distribution of targets was observed for the subset of TH-IR terminals with identifiable synaptic specializations. In addition, the proportions of GABA-labeled and unlabeled dendrites apposed to TH terminals did not differ from those previously reported for monkey prefrontal cortex. These findings indicate that DA terminals provide direct input to both excitatory and inhibitory cells in the monkey entorhinal cortex and suggest that the effects of DA are mediated through a set of targets that are common to both neo- and periallocortex.

Animals↗

ErbB3 is required for normal cerebellar and cardiac development: a comparison with ErbB2-and heregulin-deficient mice.

Heregulins bind directly to ErbB3 and ErbB4 receptors, leading to multiple dimerization possibilities including heterodimerization with the ErbB2 receptor. We have generated ErbB3-, ErbB2- and heregulin-deficient mice to assess their roles in development and differentiation. Heregulin(-/-) and ErbB2(-/-) embryos died on E10.5 due to a lack of cardiac ventricular myocyte differentiation; ErbB3(-/-) embryos survived until E13.5 exhibiting cardiac cushion abnormalities leading to blood reflux through defective valves. In ErbB3(-/-) embryos, the midbrain/hindbrain region was strikingly affected, with little differentiation of the cerebellar plate. Cranial ganglia defects, while present in all three nulls, were less severe in ErbB3(-/-) embryos. The cranial ganglia defects, along with a dramatic reduction in Schwann cells, enteric ganglia and adrenal chromaffin cells, suggests a generalized effect on the neural crest. Numerous organs, including the stomach and pancreas also exhibited anomalous development.

Adrenal Glands↗

Activation times for "emergency backup" programs.

A bench study was performed on 42 different pulse generators (PGs) to evaluate the time required to actuate and "emergency backup" (EBU) program. PGs were programmed to loss of capture before the EBU programming key was activated. Activation times for the EBU pause were measured on an ECG strip from the first noncaptured beat to the first recaptured beat while the total pause was measured between the two captured beats. Each test was performed five times. Special features for temporary threshold testing were also evaluated. Mean activation times for EBU pauses ranged from 1.46-11.90 seconds with total pauses of 2.18-12.94 seconds. Significant differences were observed for EBU activation times from the same PG but utilizing older and newer generation programmers, e.g., 10.90 (old) versus 4.54 seconds (new) for a mean EBU pause. Extreme variations existed in EBU activation times for programmers with multiple "EBU keys" for the same PG, e.g., 12.94 versus 4.96 seconds for the mean total pause. The special features for temporary threshold testing resulted in mean EBU pauses measuring 0.62-2.88 seconds and mean total pauses of 1.21-3.76 seconds. The special features were significantly faster than manual activation of the "EBU key" for regaining capture with few exceptions. Activation times were complicated by multiple programmers for the same PG and several "EBU keys" on the same programmer.

Electrocardiography↗

No output or runaway?

A 75-year-old male was implanted with a Telectronics Meta DDDR model 1250 pacemaker 47 months ago. The patient was evaluated in-office for symptomatic complaints of dizziness, palpitations, and "too slow or too fast" pulse rates. Upon examination, the device displayed sudden no output manifestations for which the device had been recalled. However, the device further displayed erratic paced rates to 200 ppm, switching between VVIR and DDDR modes. To the best of our knowledge, this is a previously unreported manifestation in this recalled device and needs to be addressed due to its potentially hazardous patient effects.

Aged↗

A verified report of spurious programming: a case study.

A case of unintentional misprogramming is described in which a DDDR pacemaker, programmed to the VVIR mode, reverted to the originally programmed parameters and mode. The misprogramming requires that a particular sequence of steps be followed and has been verified by the manufacturer. This misprogramming may be clinically significant and can be reproduced in an entire family of current pacemakers based on the same software platform.

Aged↗

Decreased sensitivity to tumour-necrosis factor but normal T-cell development in TNF receptor-2-deficient mice.

Tumour necrosis factor (TNF) elicits multiple biological effects through two distinct cell surface receptors, TNF-R1 (p55) and TNF-R2 (p75). Most TNF-mediated biological responses, such as cell death, gene induction, antiviral activity and cytokine production, have been attributed to TNF-R1 (refs 1-5). Gene targeting of this receptor confirms its role in the lethality attributable to low doses of lipopolysaccharide after sensitization with D-galactosamine; surprisingly, the toxicity of high doses of lipopolysaccharide was unaffected. The function of TNF-R2 is less well understood, although there are data supporting a role in T-cell development and the proliferation of cytotoxic T lymphocytes. To clarify the physiological role of TNF-R2, we have generated mice deficient in this receptor by gene targeting. The TNF-R2-/- mice show normal T-cell development and activity, but we find that they have increased resistance to TNF-induced death. Additionally, such mice injected subcutaneously with TNF show a dramatic decrease in tissue necrosis, indicating that this receptor plays a role in the necrotic effects of TNF.

Animals↗

Analysis of the effectiveness of in-office and transtelephonic follow-up in terms of pacemaker system complications.

A study was undertaken to determine the most effective method of pacemaker follow-up in terms of the total number of complications detected and yield per follow-up in single and dual chamber pacing systems. The analysis involved 9,786 patient records from 635 patients. The records were reviewed with respect to method of follow-up, number of chambers paced, and complications detected. Complications included: oversensing, undersensing, noncapture, pocket and diaphragmatic stimulation, pacemaker mediated tachycardia, crosstalk, pulse generator malfunction, lead malfunction, infection/erosion, premature end of service, exit block, and other miscellaneous problems. Eight thousand two hundred eighty-eight of the 9,786 follow-ups were performed in the office while 1,498 were transtelephonic. Single chamber pacing systems were implanted in 329 patients and 306 were dual chamber systems. A total of 599 complications were detected. Analysis yielded a per patient complication rate of 5.1% (single chamber) and 8.4% (dual chamber) for in-office follow-up. This compared to a transtelephonic follow-up per patient complication rate of only 0.3% (single chamber) and 1.0% (dual chamber). In-office pacemaker follow-up is significantly more effective (P < 0.001) than transtelephonic follow-up in detecting both single and dual chamber pacemaker system complications.

Equipment Failure↗

Prevalence of hepatitis B virus infection in Tonga: identifying high risk groups for immunization with hepatitis B vaccine.

A serological survey for evidence of hepatitis B virus (HBV) infection was conducted in the Kingdom of Tonga as the first step in developing a strategy for an immunization programme. There were 414 individuals from the general population plus 137 pregnant women included in the survey. HBsAg was found in 20% of the general population and 88% had one or more serologic markers of HBV infection. In the 5-9 year age group, 80% of the children had one or more markers of HBV, and in the 10-19 year age group, the prevalence was 96.4%, indicating that most transmission of HBV in the Tongans studied occurs in the young. Of the pregnant women studied, 15% were positive for HBsAg, and 57% of those positive for HBsAg were also positive for HBeAg. Evidence of delta virus infection was not found in any of 82 HBsAg positive sera tested. Surveillance data suggested that significant serious sequelae to HBV infection (cirrhosis and primary hepatocellular carcinoma) also occur in Tonga. Immunization of infants and children is the most effective strategy for reducing or eliminating HBV infection and its sequelae in developing countries like Tonga.

Adolescent↗

Postnatal development of tyrosine hydroxylase- and dopamine transporter-immunoreactive axons in monkey rostral entorhinal cortex.

Dopamine afferents from the mesencephalon appear to play a critical role in the normal development and cognitive functions of multiple areas of the primate cerebral cortex. In some regions, such as the prefrontal and motor cortices, dopamine innervation changes substantially during postnatal development. However, little is known about the postnatal maturation of dopamine afferents to the primate rostral entorhinal cortex, a periallocortical region that receives a dense dopamine innervation in adults. In this study, we used immunocytochemical techniques and antibodies against tyrosine hydroxylase and the dopamine transporter to examine the postnatal development of dopamine axons in the rostral subdivision of macaque monkey entorhinal cortex. Within animals, the axons labeled with each antibody did not differ in overall density or laminar distribution. Across development, the density of dopamine axons in layers I and VI did not change appreciably. In contrast, the density of labeled axons in layer III significantly increased by a factor of three between birth and 5-7 months of age. The timing of this change differs substantially from that observed in prefrontal cortex, where peak dopamine innervation occurs between 2 and 3 years of age. These findings, in concert with other data, suggest that developmental changes in the dopamine innervation of cortical regions may parallel the functional maturation of those areas.

Aging↗