Separate serotonin and dopamine receptors modulate the duration of post-tetanic potentiation at an aplysia synapse without affecting other aspects of synaptic transmission

We have studied the effect of the biogenic amines, serotonin and dopamine, on post-tetanic potentiation (PTP) at an identified synapse in the abdominal ganglion of Aplysia californica. We found that: (1) 10(-7) M perfused serotonin doubles the rate constant of decay of PTP. The effect is specific in that neither the size of the non-potentiated (isolated) EPSP nor the amplitude of PTP is affected. As reported previously, higher doses of serotonin will also increase the amplitude of PTP and decrease the size of the isolated EPSP; (2) 5 X 10(-7) M dopamine in the perfusate increases the rate constant of decay of PTP by about 50%. The effect is also specific in that neither PTP amplitude nor the size of the isolated EPSP is affected; (3) SQ10,631, a serotonin antagonist, blocks the effect of perfused serotonin on PTP decay rate. It does not antagonize the dopamine effect. SQ10,631 also slows the endogenous decay of PTP in some preparations which exhibit an unusually fast PTP decay rate, suggesting a naturally occurring source of serotonin within the ganglion capable of affecting the rate constant of PTP decay; (4) (+)-butaclamol, a dopamine antagonist, blocks the effect of dopamine on the rate constant of PTP decay, whereas (-)-butaclamol has little effect. Butaclamol does not block the effect of serotonin on the rate constant of PTP decay; (5) phosphodiesterase inhibitors potentiate the effect of serotonin on the rate constant of PTP decay, and cyclic AMP analogues mimic the effect of the biogenic amines, suggesting that the aminergic modulation of the rate of decay of PTP is coupled with activation of adenylate cyclase and accumulation of cyclic AMP; and (6) the evidence presented is consistent with the hypothesis that serotonin and dopamine are capable of specifically modifying the rate of change in the efficacy of transmitter release which underlies PTP. It also suggests that the two biogenic amines operate separately and in parallel via presynaptic receptor mechanisms.     

Are “Physiological” and “Psychological” Addiction Really Different? Well,No! … um,er, Yes?

The distinction often made between psychological and physiological addiction is a form of mind-body dualism. Therefore, it is a false distinction. However, this does not imply that behavioral and autonomic symptoms of addiction have the same brain substrates. In fact, they likely do not, although there is some overlap.     

New simplified radio-opaque injection technique for visualization of rat arteries

We have developed a new and simplified injection technique based on a mixture of latex and lead oxide. This injection technique is unique in its possession of both color and radio-opacity. We have developed and refined this methodology in rats, and have demonstrated it to possess superior qualities of injectability. Depiction of small vessels is highly detailed both radiographically and grossly. MICROSURGERY 17;321–323 1996 © 1997 Wiley-Liss, Inc.     

Voluntary Control of Pulse Transmission Time to the Ear

Two experiments involving voluntary control of pulse transmission time (PTT) to the ear were performed. In Experiment I (within-subject, 3 sessions), 12 male subjects attempting to control PTT with feedback showed significant bidirectional PTT changes in the target directions accompanied by parallel changes in pre-ejection period (PEP). There was no evidence of concomitant changes in respiration rate or general somatic activity. PTT control deteriorated across sessions. In Experiment II (between-subjects, 3 sessions), 10 male subjects attempting to decrease PTT with feedback produced significant PTT decreases accompanied by PEP decreases. There was marginal evidence of increases in respiration rate but no changes in general somatic activity in this condition. Five subjects attempting to increase PTT with feedback and 5 subjects attempting bidirectional PTT control without feedback showed no significant changes in PTT or PEP. The results from these experiments indicate that subjects demonstrate a modest degree of control over PTT to the ear when provided with feedback. This control of PTT is accompanied by parallel changes in PEP but is relatively free of somatic and respiratory concomitance.     

Characterization and prevalence of PITX2 microdeletions and mutations in Axenfeld-Rieger malformations

PURPOSE: Mutations of the homeodomain protein PITX2 produce Axenfeld-Rieger (AR) malformations of the anterior chamber, an autosomal dominant disorder accompanied by a 50% risk of glaucoma. Twenty-nine mutations of PITX2 have been described, with a mutational prevalence estimated between 10% and 60% in AR. In the current study, the possible role of altered PITX2 gene dosage in the etiology of AR was investigated. Gross gene deletions and duplications should alter PITX2 activity analogously to hypomorphic and hypermorphic mutations, respectively. METHODS: Sixty-four patients with AR, iridogoniodysgenesis (IGD), iris hypoplasia (IH), or anterior segment dysgenesis (ASD) were screened for PITX2 mutations by sequencing. PITX2 gene dosage was concurrently examined in these patients by real-time quantitative PCR. Microsatellite markers were used to map 4q25 microdeletions at a contig scale, as well as for haplotype analysis in an extended AR kindred. An additional 27 patients with other assorted ocular phenotypes were evaluated by similar methods, amounting to a total of 91 cases analyzed. RESULTS: Three novel mutations of PITX2 (4.7%) were identified among 64 patients with AR, IGD, IH, or ASD. Deletions of PITX2 were as frequent as mutations in our sample. Chromosome 4q25 microdeletions were physically mapped relative to several microsatellite markers in each patient. Cosegregation of AR and a PITX2 deletion was demonstrated in an extended kindred. CONCLUSIONS: Point mutations and gross deletions of PITX2 appear to produce an equivalent haploinsufficiency phenotype. Quantitative PCR is an efficient means of detecting causative PITX2 deletions in patients with AR and may increase the detection rate at this locus.     

Effect of RES `Blockade' on antibody-formation: I. Suppressed cellular and humoral haemolysin responses in mice injected with carbon particles

Antibody formation to sheep erythrocytes, as detected both at the cellular and humoral level, was suppressed in adult mice after reticulo-endothelial cell (RES) blockade induced by intraperitoneal injection of colloidal carbon. Fewer antibody plaque-forming cells (PFC) appeared in spleens of carbon pretreated mice as compared to normal controls following intraperitoneal immunization with sheep erythrocytes. The day of peak antibody response was the same, however, for both control and carbon treated animals.

There was no compensatory increase in the number of PFCs in other lymphoid organs of carbon treated animals. Similarly, carbon inoculation had no detectable effect on the number of `background' PFCs in the spleens of unstimulated mice.

The time of injection of carbon in relation to time of immunization influenced the effect since injection of carbon 24–48 hours prior to RBC injection resulted in maximum immunosuppression. Injection of carbon 4–5 days before red blood cells resulted in only partial immunosuppression. Treatment with carbon 1–2 weeks prior to immunization had no detectable effect. Similarly, injection of carbon 1 or 2 days after immunization had little or no effect on the peak plaque response.

The decrease in the amount of serum antibody to sheep red blood cells in carbon treated mice was not as marked as that which occurred on the individual cell level. However, most of the antibody in the sera of carbon treated animals was susceptible to 2-mercaptoethanol, even 1 or 2 weeks after immunization. On the other hand, serum antibody from control mice was mainly 2-mercaptoethanol sensitive only during the first week after immunization.

Immunosuppression seemed to be related to a direct effect of carbon since the supernatant fluid obtained from carbon suspensions was not suppressive. Also, washed or dialysed carbon preparations were just as effective as the original preparation in suppressing antibody responses.

     

Human conditioned compensatory response to alcohol cues: Initial evidence

Alcohol cues elicited a conditioned autonomic response that was opposite in direction to the effect of alcohol. Normal male social drinkers given placebo following four alcohol conditioning sessions showed a compensatory response consisting of decreased pulse transit time, vasomotor activity, and finger temperature. This pilot research supports the application of a classical conditioning model to human alcohol problems.     

Single pedicle microvascular transfers of the serratus anterior and latissimus dorsi muscles in rats

In the rat, the serratus anterior and latissimus dorsi muscles receive axial vascular pedicles from the thoracodorsal artery. This anatomy was confirmed by dissections, and 10 microvascular transfers of the latissimus-serratus flap on a common pedicle were performed with a 90% success rate. The flaps had an average weight of 1.8 g. This flap is a reliable small animal model for microvascular muscle transplants and contains sufficient tissue to be used in multiple biochemical assays.     

Microvascular transplant of the gastrocnemius muscle in rats

The rat gastrocnemius muscle can serve as a vascularized, innervated muscle transplant model. To establish the anatomic and technical details of this model, we performed ten gastrocnemius transplants and collected data on muscle weight, dimension, and vessel caliber from each muscle. The muscle, consisting of medial and lateral heads, is supplied by pairs of sural vessels averaging 0.2 mm in diameter. These vessels, however, can be taken in continuity with the femoral vessels (averaging 1.0–1.6 mm in diameter), which are used for transplantation. The muscles weighed an average of 2.8 g, and the average pedicle length was 24 mm. Eight of ten transplanted muscles were viable with intact circulation at 72 hr. The gastrocnemius transplant was technically reliable, and the muscle bulk and contour could allow biochemical and functional studies. Donor site morbidity limits this model to transplantation Studies. © 1993 Wiley-Liss Inc.