Summary Dietary, microbial, and inflammatory factors modulate the gut-brain axis and influence physiological processes ranging from metabolism to cognition. The gut epithelium is a principle 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 serotoninsensitive 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 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.cell density | cortex | isotropic fractionator | neuron number T he basic building blocks of information-processing circuits, the neurons and nonneuron cells of the cerebral cortex, have never been quantified in relation to identified cortical areas and regions across the entire cortical sheet. Several studies have reported total numbers of cells and neurons for the entire cortex (1-4). These reports are useful for examining cortical scaling principles across species, but because the cerebral cortex is such a heterogeneous structure with multiple parallel sensory and motor processing systems, whole-cortex cell number data have limited utility for understanding cortical information-processing circuits. Studies that have analyzed the cellular composition of particular cortical areas generally focused on a single cortical area or examined a limited number of areas. These studies (e.g., ref. 5) provide valuable comparative data, and a recent review thoughtfully considers differences between species (6). However, a global examination of the cellular composition of the cortical expanse with attention to cortical areas is clearly lacking in the published literature. A cellular and neuronal density map of the cortex of a number of species of primates and other mammals would contribute to interpretations of neuroimaging data in clinical and in cognitive neuroscience experimental settings. The density map also would improve our knowledge of processing circuits in the cortex and provide a foundation on which to build a cortical connection map (7) and on which to base neural network models of cortical function. The data presented here begin to fill this gap in our knowledge of cellular distribution patterns in the cortex.Although it seems obvious that areas and regions of the cortex vary in neuronal densities according to information-processing demands, there currently is little data on cell numbers and distribution across the cortex within and across species. Small data sets examining a few cortical areas often have generated erroneous conclusions. For example, results from one study are pervasive...

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.

2) receptive fields, often from a single ISO, were recorded from the premaxilla, the rostral dentary, the gingivae and the distal digits. These responded to a median threshold of 0.08mN. The less densely innervated caudal margins of the jaws had larger receptive fields (>100mm 2 ) and higher thresholds (13.725mN). Rapidly adapting, slowly adapting type I and slowly adapting type II responses were identified based on neuronal responses. Several rapidly adapting units responded maximally to vibrations at 20-35Hz, consistent with reports of the ISOsʼ role in detecting prey-generated water surface ripples. Despite crocodiliansʼ armored bodies, the ISOs imparted a mechanical sensitivity exceeding that of primate fingertips. We conclude that crocodilian ISOs have diverse functions, including detection of water movements, indicating when to bite based on direct contact of pursued prey, and fine tactile discrimination of items held in the jaws. Supplementary material available online at

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 are able to discriminate and respond to minute changes in environmental voltage gradients through an as-yet unknown mechanism. Here we show that the voltage-gated calcium channel CaV1.3 and 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 in the detection of specific, weak electrical signals. Both channels exhibit unique properties compared with their mammalian orthologues to support electrosensory functions: structural adaptations in CaV1.3 mediate a low voltage threshold for activation, while 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.

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.

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.

Ancient cartilaginous vertebrates, such as sharks, skates, and rays, possess specialized electrosensory organs that detect weak electric fields and relay this information to the central nervous system1–4. Sharks exploit this sensory modality for predation, whereas skates may also use it to detect signals from conspecifics5. Here we analyze shark and skate electrosensory cells to ask if discrete physiological properties could contribute to behaviorally-relevant sensory tuning. We show that sharks and skates use a similar low threshold voltage-gated calcium channel to initiate cellular activity but employ distinct potassium channels to modulate this activity. Electrosensory cells from sharks express specially adapted voltage-gated potassium channels that support large, repetitive membrane voltage spikes capable of driving near-maximal vesicular release from elaborate ribbon synapses. In contrast, skates use a calcium-activated potassium channel to produce small, tunable membrane voltage oscillations that elicit stimulus-dependent vesicular release. We propose that these sensory adaptations support amplified indiscriminate signal detection in sharks versus selective frequency detection in skates, potentially reflecting the electroreceptive requirements of these elasmobranch species. Our findings demonstrate how sensory systems adapt to suit an animal’s lifestyle or environmental niche through discrete molecular and biophysical modifications.