5-HT-immunoreactive fibers in the trigeminal nuclear complex of the rat

Summary The distribution of serotonin immunoreactive (5-HT-IR) fibers in the trigeminal nuclear complex of the rat was mapped. In the sensory nuclei, innervation appeared to be dense in areas primarily related to nociceptive afferent activity, and sparse in areas primarily related to nonnociceptive afferent activity. Specifically, the marginal and gelatinosa layers of the spinal subnucleus caudalis contained many 5-HT-IR fibers while few labeled fibers were seen in the magnocellular portion of subnucleus caudalis or in the principal sensory nucleus. The spinal subnuclei oralis and interpolaris were sparsely innervated except for a few areas which contained more 5-HT-IR fibers. The motor nucleus contained as many immunoreactive fibers as the subnucleus caudalis, although fibers in the motor nucleus were thicker and varicosities more irregularly spaced than in caudalis.This research was supported by grant BNS-79-06474 from the National Science Foundation awarded to Efrain Azmitia     

Novel actions of inverse agonists on 5-HT2C receptor systems

In cell systems where ligand-independent receptor activity is optimized (such as when receptors are overexpressed or mutated), acute treatment with inverse agonists reduces basal effector activity whereas prolonged exposure leads to sensitization of receptor systems and receptor up-regulation. Few studies, however, have reported effects of inverse agonists in systems where nonmutated receptors are expressed at relatively low density. Here, we investigated the effects of inverse agonists at human serotonin (5-HT)2C receptors expressed stably in Chinese hamster ovary cells ( approximately 250 fmol/mg protein). In these cells, there is no receptor reserve for 5-HT and 5-HT2C inverse agonists did not reduce basal inositol phosphate (IP) accumulation nor arachidonic acid (AA) release but behaved as simple competitive antagonists, suggesting that these receptors are not overexpressed. Prolonged treatment (24 h) with inverse agonists enhanced selectively 5-HT2C-mediated IP accumulation but not AA release. The enhancing effect occurred within 4 h of treatment, reversed within 3 to 4 h (after 24-h treatment), and could be blocked with neutral antagonists or weak positive agonists. The enhanced responsiveness was not due to receptor up-regulation but may involve changes in the expression of the G protein, Galphaq/11 and possibly Galpha12 and Galpha13. Interestingly, 24-h exposure to inverse agonists acting at 5-HT2C receptors also selectively enhanced IP accumulation, but not AA release, elicited by activation of endogenous purinergic receptors. These data suggest that actions of inverse agonists may be mediated through effects on receptor systems that are not direct targets for these drugs.     

Purification and sequencing of neuropeptides contained in neuron R15 of Aplysia californica.

R15 is a large identified neuron present in the abdominal ganglion of the mollusc Aplysia. Previous studies have indicated that this neuron may play a role in water balance and possibly renovascular functions. A peptidic factor contained in the neuron R15 has been shown to increase the water content of Aplysia. To determine the structure of the peptides contained in R15, we purified the extracts of 820 R15 cells by means of two steps of reverse-phase HPLC. The purification yielded a number of peptides, only one of which, R15 alpha 1, resulted in water uptake when injected into animals. Determination of the amino acid content and sequence analysis of the R15 alpha 1 peptide demonstrated that this peptide contains 38 residues, including two cysteines. The peptide failed to react with iodoacetate, indicating that the two cysteines are connected by a disulfide bridge. To confirm the assigned structure, the peptide was synthesized with a disulfide bridge. The chromatographic properties and bioactivity of the synthetic material were identical to those of the native peptide. Several other R15 peptides were inactive in the bioassay for water uptake. The sequence of one of these peptides (R15 beta) was determined, and it was established that the peptide contains 28 residues. Amino acid analysis of three other peaks was performed. One of these peaks contained a peptide (R15 beta f) whose amino acid composition suggests that it is a fragment of the R15 beta peptide. The other two peaks contained peptides with identical amino acid compositions, suggesting that they are variants of a single peptide (R15 gamma). The amino acid sequences of all the peptides identified in neuron R15 correspond to stretches of a polyprotein encoded by a recently sequenced R15 cDNA.     

Inhibition of afferent transmission in the feeding circuitry of aplysia: persistence can be as important as size

We are studying afferent transmission from a mechanoafferent, B21, to a follower, B8. During motor programs, afferent transmission is regulated so that it does not always occur. Afferent transmission is eliminated when spike propagation in B21 fails, i.e., when spike initiation is inhibited in one output region-B21's lateral process. Spike initiation in the lateral process is inhibited by the B52 and B4/5 cells. Individual B52 and B4/5-induced inhibitory postsynaptic potentials (IPSPs) in B21 differ. For example, the peak amplitude of a B4/5-induced IPSP is four times the amplitude of a B52 IPSP. Nevertheless, when interneurons fire in bursts at physiological (i.e., low) frequencies, afferent transmission is most effectively reduced by B52. Although individual B52-induced IPSPs are small, they have a long time constant and summate at low firing frequencies. Once IPSPs summate, they effectively block afferent transmission. In contrast, individual B4/5-induced IPSPs have a relatively short time constant and do not summate at low frequencies. B52 and B4/5 therefore differ in that once synaptic input from B52 becomes effective, afferent transmission is continuously inhibited. In contrast, periods of B4/5-induced inhibition are interspersed with relatively long intervals in which inhibition does not occur. Consequently, the probability that afferent transmission will be inhibited is low. In conclusion, it is widely recognized that afferent transmission can be regulated by synaptic input. Our experiments are, however, unusual in that they relate specific characteristics of postsynaptic potentials to functional inhibition. In particular we demonstrate the potential importance of the IPSP time constant.     

U.S. military officer participation in the Centers for Disease Control and Prevention's Epidemic Intelligence Service (1951-2001)

The Epidemic Intelligence Service (EIS) was created in 1951 to provide epidemiologists to investigate natural and intentional disease epidemics. From an initial class of 23 U.S. citizens, the program has evolved into a globally recognized, hands-on learning experience, accepting approximately 65 to 75 new officers each year. The first U.S. military epidemic intelligence service officer (EISO) was accepted into the program in 1994. Since that time, 12 such officers have completed, or have begun, EIS training. They have comprised 2.1% of all EISOs from 1994 to 2001 and 0.47% of all EISOs. This total has included nine Air Force veterinarians, one Army veterinarian, one Army physician, and one Navy physician. Each military EISO had the opportunity to lead investigations of significant public health events (e.g., Ebola, monkeypox, malaria, Nipah virus, West Nile fever, and anthrax outbreaks). All graduates from the military returned to active duty assignments in operational medical units, research institutes, or the intelligence community.     

Localization of responses in the somatosensory thalamus of the rat

In the monkey and cat electrophysiological studies have indicated that unit response characteristics can be correlated with anatomical divisions in the somatosensory thalamus. In the rat, however, one study has suggested that the ventrobasal (VB) and posterior (PO) complexes are not functionally distinct [7]. In the present study, therefore, an attempt was made to correlate anatomical localization and unit response characteristics in the rat. We found that in the VB complex, units responding to light touch (LT) were more common than in the PO complex (45% vs. 9%), while in the PO complex, nociceptive units were more numerous than in the VB complex (55% vs. 38%). In the VB complex LT units had a somatotopic organization; in the PO complex they did not. Within the VB complex all LT units in the ventral posteromedial nucleus had receptive fields on the head; most ventral posterolateral nucleus LT units had receptive fields on the body. These results indicate that a correlation between unit response characteristics and localization does exist in the rat.