Models of utricular bouton afferents: role of afferent-hair cell connectivity in determining spike train regularity

Vestibular bouton afferent terminals in turtle utricle can be categorized into four types depending on their location and terminal arbor structure: lateral extrastriolar (LES), striolar, juxtastriolar, and medial extrastriolar (MES). The terminal arbors of these afferents differ in surface area, total length, collecting area, number of boutons, number of bouton contacts per hair cell, and axon diameter (Huwe JA, Logan CJ, Williams B, Rowe MH, Peterson EH. J Neurophysiol 113: 2420–2433, 2015). To understand how differences in terminal morphology and the resulting hair cell inputs might affect afferent response properties, we modeled representative afferents from each region, using reconstructed bouton afferents. Collecting area and hair cell density were used to estimate hair cell-to-afferent convergence. Nonmorphological features were held constant to isolate effects of afferent structure and connectivity. The models suggest that all four bouton afferent types are electrotonically compact and that excitatory postsynaptic potentials are two to four times larger in MES afferents than in other afferents, making MES afferents more responsive to low input levels. The models also predict that MES and LES terminal structures permit higher spontaneous firing rates than those in striola and juxtastriola. We found that differences in spike train regularity are not a consequence of differences in peripheral terminal structure, per se, but that a higher proportion of multiple contacts between afferents and individual hair cells increases afferent firing irregularity. The prediction that afferents having primarily one bouton contact per hair cell will fire more regularly than afferents making multiple bouton contacts per hair cell has implications for spike train regularity in dimorphic and calyx afferents. NEW & NOTEWORTHY Bouton afferents in different regions of turtle utricle have very different morphologies and afferent-hair cell connectivities. Highly detailed computational modeling provides insights into how morphology impacts excitability and also reveals a new explanation for spike train irregularity based on relative numbers of multiple bouton contacts per hair cell. This mechanism is independent of other proposed mechanisms for spike train irregularity based on ionic conductances and can explain irregularity in dimorphic units and calyx endings.

VEGF preconditioning leads to stem cell remodeling and attenuates age-related decay of adult hippocampal neurogenesis

Several factors are known to enhance adult hippocampal neurogenesis but a factor capable of inducing a long-lasting neurogenic enhancement that attenuates age-related neurogenic decay has not been described. Here, we studied hippocampal neurogenesis following conditional VEGF induction in the adult brain and showed that a short episode of VEGF exposure withdrawn shortly after the generation of durable new vessels (but not under conditions where newly made vessels failed to persist) is sufficient for neurogenesis to proceed at a markedly elevated level for many months later. Continual neurogenic increase over several months was not accompanied by accelerated exhaustion of the neuronal stem cell (NSC) reserve, thereby allowing neurogenesis to proceed at a markedly elevated rate also in old mice. Neurogenic enhancement by VEGF preconditioning was, in part, attributed to rescue of age-related NSC quiescence. Remarkably, VEGF caused extensive NSC remodelling manifested in transition of the enigmatic NSC terminal arbor onto long cytoplasmic processes engaging with and spreading over even remote blood vessels, a configuration reminiscent of early postnatal “juvenile” NSCs. Together, these findings suggest that VEGF preconditioning might be harnessed for long-term neurogenic enhancement despite continued exposure to an “aged” systemic milieu.

Projections of single retinal ganglion cells to the visual centers: An intracellular staining study in a plethodontid salamander

The projection specificity of retinal ganglion cells and the morphology of their terminals were studied in the plethodontid salamander Plethodon jordani. In an in vitro approach, ganglion cells were stained with biocytin and reconstructed by means of light microscopy. Single retinal ganglion cells often have multiple terminal structures in the thalamus, pretectum, and tectum. The projection pattern in the diencephalic neuropils is related to the depth of the terminal arbor within the tectal fiber layer. Terminal arbors in the tectum differ in location, size, and branching pattern. The following types could be distinguished: The most superficial of the optic terminals in layer 1 are relatively small with a diameter of about 100 μm. With the exception of a few varicosities (beads) in the pretectal neuropils, their stem axons have no further collaterals or terminal arbors in the diencephalic neuropils. Intermediate terminals in layer 2 fan out to form a dense plexus with a medio-lateral extent of 180 μm on average. Some terminals in this layer show obvious antenna-like fibers reaching toward the surface of the tectum. The axons of layer 2 projecting neurons have additional collaterals and terminal arbors in the thalamus and pretectum. The deep layer 3 terminals spread out over a diameter of 400 μm on average and their degree of branching is moderate. The axons of layer 3 projecting ganglion cells have dense additional terminal arbors in the thalamus and pretectum. The deepest retinal terminals in the tectum are found within the predominantly efferent fiber layers. This type consists of an unbranched, but beaded axon which runs rostro-caudally with several bends and loops. The stem axon has an additional very dense terminal arborization in the neuropil of the nucleus Bellonci pars medialis and additional sparse collaterals in the pretectal area.

Competition and cooperation among receptor tyrosine phosphatases control motoneuron growth cone guidance in Drosophila

The neural receptor tyrosine phosphatases DPTP69D, DPTP99A and DLAR are involved in motor axon guidance in the Drosophila embryo. Here we analyze the requirements for these three phosphatases in growth cone guidance decisions along the ISN and SNb motor pathways. Any one of the three suffices for the progression of ISN pioneer growth cones beyond their first intermediate target in the dorsal muscle field. DLAR or DPTP69D can facilitate outgrowth beyond a second intermediate target, and DLAR is uniquely required for formation of a normal terminal arbor. A different pattern of partial redundancy among the three phosphatases is observed for the SNb pathway. Any one of the three suffices to allow SNb axons to leave the common ISN pathway at the exit junction. When DLAR is not expressed, however, SNb axons sometimes bypass their ventrolateral muscle targets after leaving the common pathway, instead growing out as a separate bundle adjacent to the ISN. This abnormal guidance decision can be completely suppressed by also removing DPTP99A, suggesting that DLAR turns off or counteracts a DPTP99A signal that favors the bypass axon trajectory. Our results show that the relationships among the tyrosine phosphatases are complex and dependent on cellular context. At growth cone choice points along one nerve, two phosphatases cooperate, while along another nerve these same phosphatases can act in opposition to one another.

Qualitative and quantitative features of axons projecting from caudal to rostral inferior temporal cortex of squirrel monkeys

On the basis of cortical and subcortical connections and architectonics, inferior temporal (IT) cortex of squirrel monkeys consists of a caudal region, ITC, with dorsal (ITCd) and ventral (ITCv) subdivisions; a rostral region, ITR; and possibly a third region intermediate to ITC and ITR, IT1 (Weller & Steele, 1992; Steele & Weller, 1993). The present study qualitatively and quantitatively examined the terminal arborizations of 26 axons in ITR and IT1 labeled by injections of biocytin or, in one case, horseradish peroxidase, in ITCv. The majority of axons gave rise to a single terminal arbor, with a small number branching into two overlapping or nearby arbors. Presumptive terminal specializations consisted of rounded, bead-like swellings, most often located en passant. All axons terminated in layer 4 of cortex, and most had additional terminations in layers 3 and 5. The total extent of each axon's terminal arbor was 125–750 μm dorsoventrally (mean = 360.6 μm) and 150–725 μm anteroposteriorly (mean = 328.1 μm; all values uncorrected for shrinkage). In most axons, especially those with larger terminal fields, boutons were not uniformly distributed, but formed 2–4 clumps (mean = 2.2), with a mean width of 149 μm, separated by narrower regions of fewer boutons. Based on a cluster analysis of characteristics of the 26 axons, axons projecting from caudal (ITCv) to rostral (ITR or IT1) IT cortex of squirrel monkeys comprised three groups that we called Type I, Type II, and Type III. Type I axons, the smallest in areal extent of terminal arbor, terminated predominantly in dorsal ITR. Type III axons, largest in areal extent, and Type II axons, intermediate in areal extent, terminated in ventral ITR and throughout IT1. The three classes of axons may correspond to different types of visual information entering rostral IT cortex. The clumping of boutons suggests that individual axons terminate in limited patches within their terminal fields.