Biomedical subjects

David L Paul

Publications and source records attributed to David L Paul.

24 records · Page 2Linked to original sources

PubMed2003

Beyond the gap: functions of unpaired connexon channels.

Gap junctions consist of intercellular channels that connect the cytoplasm of adjacent cells directly and allow the exchange of small molecules. These channels are unique in that they span two plasma membranes--the more orthodox ion or ligand-gated channels span only one. Each cell contributes half of the intercellular channel, and each half is known as a connexon or hemichannel. Recent studies indicate that connexons are also active in single plasma membranes and that they might be essential in intercellular signalling beyond their incorporation into gap junctions.

Animals↗

PubMed2002

Rhythmicity without synchrony in the electrically uncoupled inferior olive.

Neurons of the inferior olivary nucleus (IO) form the climbing fibers that excite Purkinje cells of the cerebellar cortex. IO neurons are electrically coupled through gap junctions, and they generate synchronous, subthreshold oscillations of membrane potential at approximately 5-10 Hz. Experimental and theoretical studies have suggested that both the rhythmicity and synchrony of IO neurons require electrical coupling. We recorded from pairs of IO neurons in slices of mouse brainstem in vitro. Most pairs of neurons from wild-type (WT) mice were electrically coupled, but coupling was rare and weak between neurons of knock-out (KO) mice for connexin36, a neuronal gap junction protein. IO cells in both WT and KO mice generated rhythmic membrane fluctuations of similar frequency and amplitude. Oscillations in neighboring pairs of WT neurons were strongly synchronized, whereas the oscillations of KO pairs were uncorrelated. Spontaneous oscillations in KO neurons were not blocked by tetrodotoxin. Spontaneously oscillating neurons of both WT and KO mice generated occasional action potentials in phase with their membrane rhythms, but only the action potentials of WT neuron pairs were synchronous. Harmaline, a beta-carboline derivative thought to induce tremor by facilitating rhythmogenesis in the IO, was injected systemically into WT and KO mice. Harmaline-induced tremors were robust and indistinguishable in the two genotypes, suggesting that gap junction-mediated synchrony does not play a role in harmaline-induced tremor. We conclude that electrical coupling is not necessary for the generation of spontaneous subthreshold oscillations in single IO neurons, but that coupling can serve to synchronize rhythmic activity among IO neurons.

Action Potentials↗

PubMed2002

Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina.

To examine the functions of electrical synapses in the transmission of signals from rod photoreceptors to ganglion cells, we generated connexin36 knockout mice. Reporter expression indicated that connexin36 was present in multiple retinal neurons including rod photoreceptors, cone bipolar cells, and AII amacrine cells. Disruption of electrical synapses between adjacent AIIs and between AIIs and ON cone bipolars was demonstrated by intracellular injection of Neurobiotin. In addition, extracellular recording in the knockout revealed the complete elimination of rod-mediated, on-center responses at the ganglion cell level. These data represent direct proof that electrical synapses are critical for the propagation of rod signals across the mammalian retina, and they demonstrate the existence of multiple rod pathways, each of which is dependent on electrical synapses.

Alkaline Phosphatase↗

PubMed2002

Connexin29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems.

Although both Schwann cells and oligodendrocytes express connexin32 (Cx32), the loss of this connexin causes demyelination only in the PNS. To determine whether oligodendrocytes might express another connexin that can function in place of Cx32, we searched for novel CNS-specific connexins using reverse transcriptase-PCR and degenerate primers. We identified Cx29, whose transcript was restricted to brain, spinal cord, and sciatic nerve. Developmental expression of Cx29 mRNA in the CNS paralleled that of other myelin-related mRNAs, including Cx32. In the CNS, Cx29 antibodies labeled the internodal and juxtaparanodal regions of small myelin sheaths, whereas Cx32 staining was restricted to large myelinated fibers. In the PNS, Cx29 expression preceded that of Cx32 and declined to lower levels than Cx32 in adulthood. In adult sciatic nerve, Cx29 was primarily localized to the innermost aspects of the myelin sheath, the paranode, the juxtaparanode, and the inner mesaxon. Cx29 displayed a striking coincidence with Kv1.2 K(+) channels, which are localized in the axonal membrane. Both Cx29 and Cx32 were found in the incisures. Cx29 expressed in N2A cells did not induce intercellular conductances but did participate in the formation of active channels when coexpressed with Cx32. Together, these data show that Cx29 and Cx32 are expressed by myelinating glial cells with distinct distributions.

Animals↗

PubMed2002

Xwnt-2 (Xwnt-2b) is maternally expressed in Xenopus oocytes and embryos.

Xwnt-2 (formerly Xwnt-2b) is a member of the Xwnt-8 class of axis-inducing Wnts. Its zygotic expression is at the prosencephalic-mesencephalic border of the early tadpole brain and above the heart primordium [Mech. Dev. 63 (1997) 199]. Here, we report that Xwnt-2 has an earlier, maternal pattern of expression. It is detected in the oocyte, egg and the developing embryo. Studies of the spatial localization of maternal Xwnt-2 show transcripts in both vegetal and animal blastomeres with enrichment in the animal hemisphere. The identification of maternal Xwnt-2 raises questions about possible roles of dorsalizing Xwnts in axial patterning of the Xenopus embryo.

Animals↗

PubMed2002

Electrical synapses in the thalamic reticular nucleus.

Neurons of the thalamic reticular nucleus (TRN) provide inhibitory input to thalamic relay cells and generate synchronized activity during sleep and seizures. It is widely assumed that TRN cells interact only via chemical synaptic connections. However, we show that many neighboring pairs of TRN neurons in rats and mice are electrically coupled. In paired-cell recordings, electrical synapses were able to mediate close correlations between action potentials when the coupling was strong; they could modulate burst-firing states even when the coupling strength was more modest. Electrical synapses between TRN neurons were absent in mice with a null mutation for the connexin36 (Cx36) gene. Surprisingly, inhibitory chemical synaptic connections between pairs of neurons were not observed, although strong extracellular stimuli could evoke inhibition in single TRN neurons. We conclude that Cx36-dependent gap junctions play an important role in the regulation of neural firing patterns within the TRN. When combined with recent observations from the cerebral cortex, our results imply that electrical synapses are a common mechanism for generating synchrony within networks of inhibitory neurons in the mammalian forebrain.

Action Potentials↗