One major issue has dominated

One major issue has dominated studies of the nematode connectome: its reproducibility. The difficulties that had to be surmounted just to assemble a complete wiring diagram precluded comparisons of the complete wiring from several different animals. Instead the earliest adult hermaphrodite wiring diagram came from a composite study that cobbled together partial wiring from 5 different animals, including a male individual for portions of the posterior nerve cords [5]. Later we compared the data for three adult hermaphrodite tails to demonstrate that a modest level of variability existed even in animals that were genetically identical [9]. As newer technologies have allowed one to compare the size and number of individual contacts for single neuron–neuron pairings, it Stiripentol sale has become clear that variation is real, and that some chemical synapses show significant differences between animals and over time during development and aging [38], [39]. These techniques have not yet been extended to measurements of GJ variability in C. elegans, but we anticipate that variation does occur. In another invertebrate with a standard set of identified neurons, the crab stomatogastric ganglion, the same basic behaviors can be generated by widely different connectome solutions among those elements [40]. Where GJs lie in parallel to chemical synaptic circuits, GJs can offer the means to modulate net output of the circuit in order to produce a stable predictable outcome [41]. Alternately, some evidence suggests that chemical synapses in the male tail modulate electrical coupling [23]. As yet we do not know enough about the physiology of the C. elegans connectome to conclude exactly how electrical circuitry works here, including the details of modulatory mechanisms. Another major concern has been that connectome studies neglect the importance for non-synaptic interactions such as the influence of neuropeptides [42], [43], [44], [51]. There is no doubt that physical wiring diagrams omit the sources and receptors for neuromodulators. In the nematode, secreted signals could connect neurons that lie far apart anatomically. Virtually all C. elegans neurons lie adjacent to a fluid space called the pseudocoelom, which is known to act as a highway for secreted extracellular signals [15]. Be that as it may, the chemical and electrical connections of the nematode connectome are becoming much better described, as envisioned by Sydney Brenner. There is a current push to uncover neurotransmitters utilized by each neuron [45], [46], and at each chemical synapse. Others are using vital dyes to observe patterns of calcium flashes within all neurons in the behaving animal [47]. Optogenetics also offers the chance to manipulate individual neurons or synapses within the system. By perturbing the connectome, one should be able to further document the importance of individual synapses during behavior [48], [49]. Combining these features with an improved description of all synapses will advance our understanding of how neurons and muscles interact to produce individual steps in behavior. It is now clear that GJs play a major role here.
Acknowledgements I thank Scott Emmons and Steven Cook for discussions on connectome details, and Chris Crocker for help on all Figures. DHH is supported by NIH OD 010943.
Introduction The ovary is the female reproductive organ responsible for the production of both the female gamete, the oocyte, and two major female sex hormones, 17β-estradiol (E2) and progesterone (P4). During embryonic development, oocytes are formed from primordial germ cells and eventually become surrounded by squamous granulosa cells in a follicular structure, termed primordial. The oocyte number encased in primordial follicles is finite at birth and oocytes remain arrested in the diplotene stage of meiosis until ovulation, or they degenerate through atresia [1]. Once the pool of primordial follicles has been depleted, either naturally or chemically-induced, ovarian senescence occurs which is termed as menopause in humans [1]. Premature ovarian failure is defined as ovarian senescence prior to age 40 and affects approximately 1% of women, with often unknown etiology [2].