Isolation of Lautropia mirabilis from oral cavities of human immunodeficiency virus-infected children.

Lautropia mirabilis, a pleomorphic, motile, gram-negative coccus, has been isolated from the oral cavities of 32 of 60 (53.3%) children infected with human immunodeficiency virus (HIV) and 3 of 25 (12.0%) HIV-uninfected controls; the association of L. mirabilis isolation with HIV infection is significant (P < 0.001). All children in the study, both HIV-infected children and controls, were born to HIV-infected mothers. The presence of this bacterium was not associated with clinical disease in these children. The HIV-infected children with L. mirabilis did not differ from the HIV-infected children without L. mirabilis in immunological status, clinical status, or systemic medications. The role of HIV infection itself or concomitant factors in the establishment of L. mirabilis in the oral cavity remains to be elucidated.

Molluscan memory of injury: evolutionary insights into chronic pain and neurological disorders.

Molluscan preparations have yielded seminal discoveries in neuroscience, but the experimental advantages of this group have not, until now, been complemented by adequate molecular or genomic information for comparisons to genetically defined model organisms in other phyla. The recent sequencing of the transcriptome and genome of Aplysia californica, however, will enable extensive comparative studies at the molecular level. Among other benefits, this will bring the power of individually identifiable and manipulable neurons to bear upon questions of cellular function for evolutionarily conserved genes associated with clinically important neural dysfunction. Because of the slower rate of gene evolution in this molluscan lineage, more homologs of genes associated with human disease are present in Aplysia than in leading model organisms from Arthropoda (Drosophila) or Nematoda (Caenorhabditis elegans). Research has hardly begun in molluscs on the cellular functions of gene products that in humans are associated with neurological diseases. On the other hand, much is known about molecular and cellular mechanisms of long-term neuronal plasticity. Persistent nociceptive sensitization of nociceptors in Aplysia displays many functional similarities to alterations in mammalian nociceptors associated with the clinical problem of chronic pain. Moreover, in Aplysia and mammals the same cell signaling pathways trigger persistent enhancement of excitability and synaptic transmission following noxious stimulation, and these highly conserved pathways are also used to induce memory traces in neural circuits of diverse species. This functional and molecular overlap in distantly related lineages and neuronal types supports the proposal that fundamental plasticity mechanisms important for memory, chronic pain, and other lasting alterations evolved from adaptive responses to peripheral injury in the earliest neurons. Molluscan preparations should become increasingly useful for comparative studies across phyla that can provide insight into cellular functions of clinically important genes.

ANALYSIS OF SEROTONERGIC MODULATION OF NEURONS INVOLVED IN TWO DEFENSIVE BEHAVIORS IN APLYSIA CALIFORNICA (CYCLIC-AMP, AROUSAL, CALCIUM, POTASSIUM)

Sensitization is a simple form of learning which refers to an enhancement of a behavioral response resulting from an exposure to a novel stimulus. While sensitization is found throughout the animal world, little is known regarding the underlying neural mechanisms. By taking advantage of the simple nervous system of the marine mollusc Aplysia, I have begun to examine the cellular and molecular mechanisms underlying this simple form of learning. In an attempt to determine the generality of the mechanisms of neuromodulation underlying sensitization, I have investigated and compared the modulation of neurons involved in two defensive behaviors in Aplysia, the defensive inking response and defensive tail withdrawal.^ The motor neurons that produce the defensive release of ink receive a slow decreased conductance excitatory postsynaptic potential (EPSP) in response to sensitizing stimuli. Using electrophysiological techniques, it was found that serotonin (5-HT) mimicked the physiologically produced slow EPSP. 5-HT produced its response through a reduction in a voltage-independent conductance to K('+). The 5-HT sensitive K('+) conductance of the ink motor neurons was separate from the fast K('+), delayed K('+), and Ca('2+)-activated K('+) conductances found in these and other molluscan neurons. 5-HT was shown to produce a decrease in K('+) conductance in the ink motor neurons through an elevation of cellular cAMP.^ The mechanosensory neurons that participate in the defensive tail withdrawal response are also modulated by sensitizing stimuli through the action of 5-HT. Using electrophysiological techniques, it was found that 5-HT modulated the tail sensory neurons through a reduction in a voltage-dependent conductance to K('+). The serotonin-sensitive K('+) conductance was found to be largely a Ca('2+)-activated K('+) conductance. Much like the ink motor neurons, 5-HT produced its modulation through an elevation of cellular cAMP. While the actual K('+) conductance modulated by 5-HT in these two classes of neurons differs, the following generalizations can be made: (1) the effects of sensitizing stimuli are mimicked by 5-HT, (2) 5-HT produces its effect through an elevation of cellular cAMP, and (3) the conductance to K('+) is modulated by 5-HT. ^