Morphine and ACTH1–24: correlative behavioral excitations following microinjections in rat periaqueductal gray

Rats implanted with bilateral cannulas in the periaqueductal gray exhibited similar behavioral excitations following microinjections of morphine sulphate and ACTH_1–24. Injections were more effective when the sites were located within rather than below the periaqueductal gray. Analgesia was observed following morphine but not ACTH microinjection. These results confirm that morphine exerts a dual action, inhibitory (i.e. analgesic) and excitatory, with ACTH mimicking only the latter action.     

The midbrain central gray substance as a highly sensitive neural structure for the production of ultrasonic vocalization in the rat

To test whether there were any functional differences between the central gray substance (PVG) and other neural structures for the production of ultrasonic vocalization in the rat, an electrical stimulation experiment was systematically undertaken in diencephalic and mesencephalic tegmental regions. The sound production sensitivity to electrical stimulation was the highest in PVG. This suggested that the periventricular fiber system of Schu¨tz's bundle might be a possible neural structure underlying sound emission in the rat.     

Hypothalamic hamartoma,gelastic epilepsy,precocious puberty--a diffuse cerebral dysgenesis

Childhood epileptic syndrome characterized by early onset gelastic seizures, hypothalamic hamartoma and precocious puberty is well recognized though rare. We report association of agenesis of corpus callosum, Dandy–Walker complex and heterotopic gray matter with this childhood epileptic syndrome which is hitherto an unreported association. The child showed a satisfactory response to gonadotropin releasing hormone agonist.     

In vivo magnetic resonance imaging of the human cervical spinal cord at 3 Tesla

PURPOSE: To demonstrate the feasibility of obtaining high-quality magnetic resonance (MR) images of the human cervical spinal cord in vivo at a magnetic field strength of 3 T and to optimize the signal contrast between gray matter, white matter, and cerebrospinal fluid (CSF) on 2D gradient recalled echo (GRE) images of the cervical spinal cord. MATERIALS AND METHODS: Using a custom-built, anatomically molded radio frequency (RF) surface coil, the repetition time and flip angle of a 2D GRE sequence were systematically varied in five volunteers to assess tissue contrast in the cervical spinal cord. RESULTS: The 2D GRE parameters for an optimal balance between gray-white matter and CSF-white matter contrast at 3 T were determined to be a time-to-repetition (TR) of 2000 msec and a flip angle of 45 degrees, with the constant short time-to-echo (TE) of 12 msec used in this study. Excellent tissue contrast and visualization of the internal anatomy of the spinal cord was demonstrated reproducibly in eight subjects using these optimal parameters. CONCLUSION: This study demonstrates that imaging the cervical spinal cord and delineating internal spinal cord structures such as gray and white matter is feasible at 3 T.     

On serotonin and experimental anxiety

Abstract Background. This review describes the development of a research line on the role of serotonin (5-HT) in experimental anxiety that was initiated in 1969, in the laboratory founded by P.B. Dews, W.H. Morse and R.T. Kelleher at the Harvard Medical School, and has evolved until this date. Results. Initially, it was found that two non-selective 5-HT receptor antagonists released punished responding in pigeons with a magnitude comparable to that of benzodiazepine anxiolytics. This result was one of the key evidences that led to the concept that 5-HT enhanced anxiety by acting both in the forebrain and in the periaqueductal gray matter (PAG). Further evidence supported this hypothesis regarding the forebrain, but results with electrical stimulation and intracerebral drug injection into the PAG indicated that 5-HT inhibited aversive behavior evoked from this area. As a result, it has been suggested that 5-HT has a dual role in the regulation of defense, namely enhancing learned responses to potential or distal threat through actions in the forebrain while inhibiting unconditioned responses to proximal threat by acting on the PAG. The former would be related to generalized anxiety and the latter to panic disorder. To test this hypothesis, a new animal model, named the elevated T-maze, has been designed. It consists of one arm enclosed by walls that is perpendicular to two open arms elevated from the floor. The same rat performs two tasks, namely inhibitory avoidance of the elevated open arms, representing conditioned anxiety and one-way escape from one of the open arms, representative of unconditioned fear. Conclusion. The differential effects of drugs acting on 5-HT observed in the two tasks of the ETM generally support the hypothesis under scrutiny. Electronic Publication     

Ethanol withdrawal results in aberrant membrane properties and synaptic responses in periaqueductal gray neurons associated with seizure susceptibility

The midbrain periaqueductal gray (PAG) is implicated as a component of the neuronal network for ethanol withdrawal (ETX) seizures and in other forms of audiogenic seizure (AGS) in rats. Previous in vivo experiments suggest that neurons in the ventrolateral PAG (VL PAG) are required for generation of the clonic and tonic seizure behaviors of AGS. During these seizures, PAG neuronal firing rates increase markedly, but the intracellular events, contributing to this phenomenon, have not been characterized. In the present in vitro study, intracellular current-clamp recordings were obtained from 115 control VL PAG neurons and 71 neurons during ETX. The amount of depolarizing current that needed to be injected into ETX neurons in order to generate an action potential (AP) (N=40) was significantly less than control (N=52). ETX also yielded a significant leftward shift in the frequency-current curve of VL PAG neurons. VL PAG neurons during ETX had significantly enhanced spike firing tendencies, but the firing pattern was similar in ETX and control. ETX significantly increased the incidence of spontaneous APs and the frequency of firing above those in control. A number of cellular properties [e.g. resting membrane potential (RMP), amplitude of AP, AP width at half-height, input resistance and time constant] did not differ significantly between ETX and control neurons. The current-voltage (I-V) relationships of the ETX and control VL PAG neurons were nearly linear between RMP and 80 mV more negative than RMP, whereas the I-V relation was non-linear beyond this range. Stimulation in the dorsolateral PAG in either ETX or control neurons evoked a fast excitatory postsynaptic potential (EPSP) and a slow inhibitory postsynaptic potential (IPSP). The stimulus intensities required to evoke EPSPs were significantly lower than control in neurons during ETX. Epileptiform firing was observed commonly (20%) during ETX but was never seen in control rats. Paired-pulse responses evoked paired-pulse inhibition in approximately 80% of VL PAG neurons from control rats (N=38), which was significantly above the incidence (12%) of this pattern during ETX (N=25). Paired-pulse facilitation was significantly more common (88%) in VL PAG neurons (N=25) during ETX compared to approximately 20% in controls (N=38). These aberrant membrane and synaptic properties provide direct evidence regarding the basis of the hyperexcitability observed in VL PAG neurons in vivo that contribute to propagation mechanisms of clonic and tonic convulsions, occurring during ETX.     

Complement activated C4d immunoreactive oligodendrocytes delineate small cortical plaques in multiple sclerosis

C4d-immunoreactive complement-activated oligodendrocytes (C4d-CAOs) have been described in several neurodegenerative diseases but have not been studied in multiple sclerosis (MS). Here we report that such CAOs delineate miniature MS plaques of 300-500 mum diameter. They are devoid of myelin and are surrounded by a rim of activated microglia intermingled with the C4d-CAOs. Although C4d-immunostained periaxonal oligodendroglial processes are often swollen, the axons of passage appear undamaged and extend through the demyelinated plaque area. No immunostaining with other components of the complement cascade (C1q-C9) was observed in association with these miniature plaques. However, in large MS lesions, C1q-C9 immunoreactive fibers were present, indicating complete activation of the complement cascade in these more developed lesions. It is possible that the miniature plaques, bordered by C4d-CAOs, represent the earliest stage of plaque development, preceding even the larger, transient plaques frequently observed in serial MRI studies. The association of CAOs with miniature areas of demyelination suggests a direct attack on oligodendroglial cells by the early complement components as an initiating event in MS. Incomplete complement activation indicates that this step may be reversible, whereas full and persistent activation as observed in large MS lesions may lead to death of oligodendroglia with permanent axonal damage.     

Sensory,hormonal, and neural control of maternal aggression in laboratory rodents

Parental animals of many rodent species display fierce and persistent aggression toward unfamiliar conspecifics that appears to protect their often altricial and defenseless young. We herein review studies of the sensory, hormonal, neuroanatomical, and neurochemical mechanisms underlying maternal aggression in laboratory rodents. The relationship between maternal aggression and fearfulness or anxiety is also discussed.     

Variation of micronucleated erythrocytes in peripheral blood of Sciurus aureogaster in relation to age: an increment of micronucleated polychromatic erythrocytes after the administration of colchicine

In some species, in which the human is included, the influence of age in the variation in the number of micronucleated erythrocytes (MNE) is known. In the present work we show how the process of aging influences the number of spontaneous MNE in the gray squirrel (Sciurus aureogaster). Because of the difficulty of knowing the age of each animal, 69 animals were weighed at their arrival to the laboratory and at the start of sample taking, with the supposition that the heaviest animals were the oldest and those with the lightest weight were the youngest. The major number of MNE was found in the younger animals, whereas the adults displayed less MNE (P < 0.0001). A group of 11 animals were sampled every 15 days over a period of 6 months, and the number of MNE were found to decrease with an increment in the weight in conformity with the time elapsed. These results showed that in the gray squirrel, the number of spontaneous MNE in peripheral blood depend on age. An additional interesting datum about the increment of MNE after the administration of colchicine is shown.     

Quantitative 1H-MRS of healthy human cortex, hippocampus, and thalamus: metabolite concentrations, quantification precision, and reproducibility

PURPOSE: To evaluate metabolite concentrations in cortical gray matter, hippocampus, and thalamus of healthy adults, and to investigate precision and reproducibility of quantitative proton magnetic resonance spectroscopy (1H-MRS) in these gray matter regions. MATERIALS AND METHODS: Quantitative single-voxel short echo-time spectra were obtained from healthy human cortex, hippocampus, and thalamus. Subjects were examined twice. Metabolite concentrations, quantification precision, and reproducibility were determined. RESULTS: There were no significant differences between test and retest measurements. Regional differences were observed with respect to metabolite concentrations, quantification precision, and reproducibility. Quantification precision and reproducibility of N-acetylaspartate and N-acetyl aspartylglutamate (tNAA), creatine and phosphocreatine (tCr), choline-containing compounds (Cho), and myo-inositol (myo-Ins), were better than those of glutamate (Glu) and glutamine (Gln). Generally, precision and reproducibility were better in cortex than in hippocampus or thalamus. The quantification precision was shown to correlate both with reproducibility and spectral linewidth. CONCLUSION: The reliability of quantitative MRS depends on the metabolite concerned, its concentration, and on the brain area studied. Moreover, the quantification precision of a metabolite in a single spectrum appears to be a reliable measure for its reproducibility in a longitudinal study.