Duncan B. Leitch

Neuron densities vary across and within cortical areas in primates

The numbers and proportion of neurons in areas and regions of cortex were determined for a single cortical hemisphere from two prosimian galagos, one New World owl monkey, one Old World macaque monkey, and one baboon. The results suggest that there is a common plan of cortical organization across the species examined here and also differences that suggest greater specializations in the Old World monkeys. In all primates examined, primary visual cortex (V1) was the most neuron-dense cortical area and the secondary visual areas had higher-than-average densities. Primary auditory and somatosensory areas tended to have high densities in the Old World macaque and baboon. Neuronal density varies less across cortical areas in prosimian galagos than in the Old World monkeys. Thus, cortical architecture varies greatly within and across primate species, but cell density is greater in cortex devoted to the early stages of sensory processing.

Manganese Exposure is Cytotoxic and Alters Dopaminergic and GABAergic Neurons within the Basal Ganglia

Manganese is an essential nutrient, integral to proper metabolism of amino acids, proteins and lipids. Excessive environmental exposure to manganese can produce extrapyramidal symptoms similar to those observed in Parkinson’s disease (PD). We used in vivo and in vitro models to examine cellular and circuitry alterations induced by manganese exposure. Primary mesencephalic cultures were treated with 10–800 μM manganese chloride which resulted in dramatic changes in the neuronal cytoskeleton even at subtoxic concentrations. Using cultures from mice with red fluorescent protein driven by the tyrosine hydroxylase (TH) promoter, we found that dopaminergic neurons were more susceptible to manganese toxicity. To understand the vulnerability of dopaminergic cells to chronic manganese exposure, mice were given i.p. injections of MnCl2 for 30 days. We observed a 20% reduction in TH‐positive neurons in the substantia nigra pars compacta (SNpc) following manganese treatment. Quantification of Nissl bodies revealed a widespread reduction in SNpc cell numbers. Other areas of the basal ganglia were also altered by manganese as evidenced by the loss of glutamic acid decarboxylase 67 in the striatum. These studies suggest that acute manganese exposure induces cytoskeletal dysfunction prior to degeneration and that chronic manganese exposure results in neurochemical dysfunction with overlapping features to PD.

Cellular scaling rules of insectivore brains

Insectivores represent extremes in mammalian body size and brain size, retaining various “primitive” morphological characteristics, and some species of Insectivora are thought to share similarities with small-bodied ancestral eutherians. This raises the possibility that insectivore brains differ from other taxa, including rodents and primates, in cellular scaling properties. Here we examine the cellular scaling rules for insectivore brains and demonstrate that insectivore scaling rules overlap somewhat with those for rodents and primates such that the insectivore cortex shares scaling rules with rodents (increasing faster in size than in numbers of neurons), but the insectivore cerebellum shares scaling rules with primates (increasing isometrically). Brain structures pooled as “remaining areas” appear to scale similarly across all three mammalian orders with respect to numbers of neurons, and the numbers of non-neurons appear to scale similarly across all brain structures for all three orders. Therefore, common scaling rules exist, to different extents, between insectivore, rodent, and primate brain regions, and it is hypothesized that insectivores represent the common aspects of each order. The olfactory bulbs of insectivores, however, offer a noteworthy exception in that neuronal density increases linearly with increasing structure mass. This implies that the average neuronal cell size decreases with increasing olfactory bulb mass in order to accommodate greater neuronal density, and represents the first documentation of a brain structure gaining neurons at a greater rate than mass. This might allow insectivore brains to concentrate more neurons within the olfactory bulbs without a prohibitively large and metabolically costly increase in structure mass.

Enterochromaffin Cells Are Gut Chemosensors that Couple to Sensory Neural Pathways

Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principal site for detecting such agents, but precisely how it communicates with neural elements is poorly understood. Serotonergic enterochromaffin (EC) cells are proposed to fulfill this role by acting as chemosensors, but understanding how these rare and unique cell types transduce chemosensory information to the nervous system has been hampered by their paucity and inaccessibility to single-cell measurements. Here, we circumvent this limitation by exploiting cultured intestinal organoids together with single-cell measurements to elucidate intrinsic biophysical, pharmacological, and genetic properties of EC cells. We show that EC cells express specific chemosensory receptors, are electrically excitable, and modulate serotonin-sensitive primary afferent nerve fibers via synaptic connections, enabling them to detect and transduce environmental, metabolic, and homeostatic information from the gut directly to the nervous system.

The Star-Nosed Mole Reveals Clues to the Molecular Basis of Mammalian Touch

Little is known about the molecular mechanisms underlying mammalian touch transduction. To identify novel candidate transducers, we examined the molecular and cellular basis of touch in one of the most sensitive tactile organs in the animal kingdom, the star of the star-nosed mole. Our findings demonstrate that the trigeminal ganglia innervating the star are enriched in tactile-sensitive neurons, resulting in a higher proportion of light touch fibers and lower proportion of nociceptors compared to the dorsal root ganglia innervating the rest of the body. We exploit this difference using transcriptome analysis of the star-nosed mole sensory ganglia to identify novel candidate mammalian touch and pain transducers. The most enriched candidates are also expressed in mouse somatosesensory ganglia, suggesting they may mediate transduction in diverse species and are not unique to moles. These findings highlight the utility of examining diverse and specialized species to address fundamental questions in mammalian biology.

Molecular basis of ancestral vertebrate electroreception

Elasmobranch fishes, including sharks, rays, and skates, use specialized electrosensory organs called ampullae of Lorenzini to detect extremely small changes in environmental electric fields. Electrosensory cells within these ampullae can discriminate and respond to minute changes in environmental voltage gradients through an unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and the big conductance calcium-activated potassium (BK) channel are preferentially expressed by electrosensory cells in little skate (Leucoraja erinacea) and functionally couple to mediate electrosensory cell membrane voltage oscillations, which are important for the detection of specific, weak electrical signals. Both channels exhibit unique properties compared with their mammalian orthologues that support electrosensory functions: structural adaptations in CaV1.3 mediate a low-voltage threshold for activation, and alterations in BK support specifically tuned voltage oscillations. These findings reveal a molecular basis of electroreception and demonstrate how discrete evolutionary changes in ion channel structure facilitate sensory adaptation.

Function of the appendages in tentacled snakes (Erpeton tentaculatus)

SUMMARY We investigated the function of the tentacles in aquatic, piscivorous tentacled snakes (Erpeton tentaculatus) by examining anatomy, peripheral innervation, and the response properties of primary afferents. We also investigated visual and somatosensory responses in the optic tectum and documented predatory strikes to visual stimuli and under infrared illumination. Our results show the tentacles are sensitive mechanoreceptors that respond to water movements. They are innervated by rami of the maxillary and ophthalmic branches of the trigeminal nerve and contain a dense array of fine terminal neurites that cross the interior of the tentacle orthogonal to its long axis. The optic tectum contained a retinotopic map of contralateral receptive fields with superior fields represented dorsally in the tectum, inferior fields represented laterally, nasal fields represented rostrally, and temporal fields represented caudally. Large somatosensory receptive fields were identified in deeper layers of the tectum and were in approximate register with overlying visual fields. Tentacled snakes struck accurately at a simulated digital fish, indicating that visual cues are sufficient to guide strikes, but they also captured fish under infrared illumination, suggesting water movements alone could be used to localize prey. We conclude the tentacles are mechanosensors that are used to detect fish position based on water movements and that visual and mechanosensory cues may be integrated in the tectum to enhance localization when visual cues are reduced.

A Star in the Brainstem Reveals the First Step of Cortical Magnification

A fundamental question in the neurosciences is how central nervous system (CNS) space is allocated to different sensory inputs. Yet it is difficult to measure innervation density and corresponding representational areas in the CNS of most species. These measurements can be made in star-nosed moles (Condylura cristata) because the cortical representation of nasal rays is visible in flattened sections and afferents from each ray can be counted. Here we used electrophysiological recordings combined with sections of the brainstem to identify a large, visible star representation in the principal sensory nucleus (PrV). PrV was greatly expanded and bulged out of the brainstem rostrally to partially invade the trigeminal nerve. The star representation was a distinct PrV subnucleus containing 11 modules, each representing one of the nasal rays. The 11 PrV ray representations were reconstructed to obtain volumes and the largest module corresponded to ray 11, the moles tactile fovea. These measures were compared to fiber counts and primary cortical areas from a previous investigation. PrV ray volumes were closely correlated with the number of afferents from each ray, but afferents from the behaviorally most important, 11th ray were preferentially over-represented. This over-representation at the brainstem level was much less than at the cortical level. Our results indicate that PrV provides the first step in magnifying CNS representations of important afferents, but additional magnification occurs at higher levels. The early development of the 11th, foveal appendage could provide a mechanism for the most important afferents to capture the most CNS space.

Organization of the spinal trigeminal nucleus in Star-Nosed Moles

Somatosensory inputs from the face project to multiple regions of the trigeminal nuclear complex in the brainstem. In mice and rats, three subdivisions contain visible representations of the mystacial vibrissae, the principal sensory nucleus, spinal trigeminal subnucleus interpolaris, and subnucleus caudalis. These regions are considered important for touch with high spatial acuity, active touch, and pain and temperature sensation, respectively. Like mice and rats, the star‐nosed mole (Condylura cristata) is a somatosensory specialist. Given the visible star pattern in preparations of the star‐nosed mole cortex and the principal sensory nucleus, we hypothesized there were star patterns in the spinal trigeminal nucleus subnuclei interpolaris and caudalis. In sections processed for cytochrome oxidase, we found star‐like segmentation consisting of lightly stained septa separating darkly stained patches in subnucleus interpolaris (juvenile tissue) and subnucleus caudalis (juvenile and adult tissue). Subnucleus caudalis represented the face in a three‐dimensional map, with the most anterior part of the face represented more rostrally than posterior parts of the face. Multiunit electrophysiological mapping was used to map the ipsilateral face. Ray‐specific receptive fields in adults matched the CO segmentation. The mean areas of multiunit receptive fields in subnucleus interpolaris and caudalis were larger than previously mapped receptive fields in the moles principal sensory nucleus. The proportion of tissue devoted to each rays representation differed between the subnucleus interpolaris and the principal sensory nucleus. Our finding that different trigeminal brainstem maps can exaggerate different parts of the face could provide new insights for the roles of these different somatosensory stations. J. Comp. Neurol. 522:3335–3350, 2014.

Barrelettes without Barrels in the American Water Shrew

Water shrews (Sorex palustris) depend heavily on their elaborate whiskers to navigate their environment and locate prey. They have small eyes and ears with correspondingly small optic and auditory nerves. Previous investigations have shown that water shrew neocortex is dominated by large representations of the whiskers in primary and secondary somatosensory cortex (S1 and S2). Flattened sections of juvenile cortex processed for cytochrome oxidase revealed clear borders of the whisker pad representation in S1, but no cortical barrels. We were therefore surprised to discover prominent barrelettes in brainstem of juvenile water shrews in the present investigation. These distinctive modules were found in the principal trigeminal nucleus (PrV), and in two of the three spinal trigeminal subnuclei (interpolaris – SpVi and caudalis – SpVc). Analysis of the shrews whisker pad revealed the likely relationship between whiskers and barrelettes. Barrelettes persisted in adult water shrew PrV, but barrels were also absent from adult cortex. Thus in contrast to mice and rats, which have obvious barrels in primary somatosensory cortex and less clear barrelettes in the principal nucleus, water shrews have clear barrelettes in the brainstem and no barrels in the neocortex. These results highlight the diverse ways that similar mechanoreceptors can be represented in the central nervous systems of different species.