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Native lotus (Nelumbo nucifera G.) seed starch (LSS) was single- and dual-modified by heat-moisture treatment (HMT), ultrasonication (US), HMT followed by the US (HMT-US), and the US followed by HMT (US-HMT). The modified lotus seed starch (LSS) was evaluated for its physicochemical, pasting, thermal, and rheological properties and in vitro digestibility. All treatments decreased the swelling power (10.52-14.0 g/g), solubility (12.20-15.95 %), and amylose content (23.71-25.67 %) except for ultrasonication (17.67 g/g, 17.90 %, 29.09 %, respectively) when compared with native LSS (15.05 g/g, 16.12 %, 27.12 %, respectively). According to the rheological study, G' (1665-4004 Pa) was greater than G″ (119-308 Pa) for all LSS gel samples demonstrating their elastic character. Moreover, gelatinization enthalpy (17.56-16.05 J/g) increased in all treatments compared to native LSS (15.38 J/g). Ultrasonication treatment improved the thermal stability of LSS. The digestibility results showed that dual modification using HMT and US significantly enhanced resistant starch (RS) and reduced slowly digestible starch (SDS) in LSS. Cracks were observed on the surface of the modified LSS granules. Peak viscosity decreased in all modified starches except for ultrasonication, suggesting their resistance to shear-thinning during cooking, making them ideal weaning food components. The results obtained after different modifications in this study could be a useful ready reference to select appropriate modification treatments to produce modified LSS with desired properties depending on their end-use., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

The potential of alkali-assist photocatalytic (AAP) pretreatment to overcome the recalcitrant nature of lignocellulose biomass, i.e. rice straw (RS), was investigated in the present study. Box-Behenken Design (BBD) using standard response surface methodology (RSM) approach was considered to obtain optimal conditions for maximum delignification. The model was designed with three variables: alkali concentration (NaOH, 0-3% w/v), photocatalyst (TiO 2 NPs (titania nanoparticles), 0-1 g/L) and pretreatment time (30-240 min). The availability of cellulose was increased by 96.73%, while the concentration of lignin and hemicellulose decreased by 73.89%, and 71.79%, respectively, at a combination of 1.5% NaOH, 0.5 g/L TiO 2 NPs and 135 min pretreatment time. The structural and morphological alterations in the RS were assessed via Fourier Transform Infrared spectroscopy (FTIR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) both before and after AAP pretreatment. The FTIR measurement indicated that the original RS included a significant quantity of lignin, which was eliminated after the pretreatment procedure. The XRD pattern demonstrates that cellulose crystallinity is significantly affected by the pretreatment. The SEM analysis revealed structural distortion and surface porosity from the pretreatment procedure., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Microplastics, which have a diameter of less than 5 mm, are becoming an increasingly prevalent contaminant in terrestrial and aquatic ecosystems due to the dramatic increase in plastic production to 390.7 million tonnes in 2021. Among all the plastics produced since 1950, nearly 80% ended up in the environment or landfills and eventually reached the oceans. Currently, 82-358 trillion plastic particles, equivalent to 1.1-4.9 million tonnes by weight, are floating on the ocean's surface. The interactions between microorganisms and microplastics have led to the transportation of other associated pollutants to higher trophic levels of the food chain, where microplastics eventually reach plants, animals, and top predators. This review paper focuses on the interactions and origins of microplastics in diverse environmental compartments that involve terrestrial and aquatic food chains. The present review study also critically discusses the toxicity potential of microplastics in the food chain. This systematic review critically identified 206 publications from 2010 to 2022, specifically reported on microplastic transport and ecotoxicological impact in aquatic and terrestrial food chains. Based on the ScienceDirect database, the total number of studies with "microplastic" as the keyword in their title increased from 75 to 4813 between 2010 and 2022. Furthermore, various contaminants are discussed, including how microplastics act as a vector to reach organisms after ingestion. This review paper would provide useful perspectives in comprehending the possible effects of microplastics and associated contaminants from primary producers to the highest trophic level (i.e. human health)., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: Drug-induced liver injury (DILI) is the most challenging and thought-provoking liver problem for hepatologists owing to unregulated medication usage in medical practices, nutritional supplements, and botanicals. Due to underreporting, analysis, and identification issues, clinically evaluated medication hepatotoxicity is prevalent yet hard to quantify., Purpose: This review's primary objective is to thoroughly compare pharmaceutical drugs and herbal compounds that have undergone clinical trials, focusing on their metabolic mechanisms contributing to the onset of liver illnesses and their hepatoprotective effects., Methods: The data was gathered from several online sources, such as PubMed, Scopus, Google Scholar, and Web of Science, using appropriate keywords., Results: The prevalence of conventional and herbal medicine is rising. A comprehensive understanding of the metabolic mechanism is necessary to mitigate the hepatotoxicity induced by drugs and facilitate the incorporation or substitution of herbal medicine instead of pharmaceuticals. Moreover, pre-clinical pharmacological research has the potential to facilitate the development of natural products as therapeutic agents, displaying promising possibilities for their eventual clinical implementation., Conclusions: Acetaminophen, isoniazid, rifampicin, diclofenac, and pyrogallol have been identified as the most often reported synthetic drugs that produce hepatotoxicity by oxidative stress, inflammation, apoptosis, and fibrosis during the last several decades. Due to their ability to downregulate many factors (such as cytokines) and activate several enzyme/enzyme systems, herbal substances (such as Gingko biloba extract, curcumin, resveratrol, and silymarin) provide superior protection against harmful mechanisms which induce hepatotoxicity with fewer adverse effects than their synthetic counterparts., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Lotus (Nelumbo nucifera G.) rhizomes are an under-utilized and sustainable starch source that constitutes up to 20 % starch. The review mainly focused on the extraction methods of starch, the chemical composition of LRS, and techno-functional characteristics such as swelling power, solubility, in vitro digestibility, pasting property, and gelatinization is highlighted in LRS review. Lotus rhizome starch (LRS) is also used as a water retention agent, thickening, gelling, stabilizing, and filling in food and non-food applications. Native starch has limited functional characteristics in food applications so by modifying the starch, functional characteristics are enhanced. Single and dual treatment processes are available to enhance microstructural properties, resistant starch, techno-functional, morphological, and, film-forming properties. Compared with other starch sources, there is a lack of systematic information on the LRS. Many industries are interested in developing food products based on starch such as nanoparticles, hydrogels, edible films, and many others. Additionally, there are several recommendations to improve the applications in the food industry. Finally, we provide an outlook on the future possibility of LRS., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Depleting fossil fuels and net carbon emissions associated with their burning have driven the need to find alternative energy sources. Biofuels are near-perfect candidates for alternative energy sources as they are renewable and account for no net CO 2 emissions. However, biofuel production must overcome various challenges to compete with conventional fuels. Conventional methods for bioconversion of biomass to biofuel include chemical, thermochemical, and biological processes. Substrate selection and processing, low yield, and total cost of production are some of the main issues associated with biofuel generation. Recently, the uses of nanotechnology and nanoparticles have been explored to improve the biofuel production processes because of their high adsorption, high reactivity, and catalytic properties. The role of these nanoscale particles and nanocatalysts in biomass conversion and their effect on biofuel production processes and yield are discussed in the present article. The applicability of nanotechnology in production processes of biobutanol, bioethanol, biodiesel, biohydrogen, and biogas under biorefinery approach are presented. Different types of nanoparticles, and their function in the bioprocess, such as electron transfer, pretreatment, hydrolysis, microalgae cultivation, lipid extraction, dark and photo fermentation, immobilization, and suppression of inhibitory compounds, are also highlighted. Finally, the current and potential applications of nanotechnology in biorefineries are also discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

There is a significant concern about the accessibility of uncontaminated and safe drinking water, a fundamental necessity for human beings. This concern is attributed to the toxic micropollutants from several emission sources, including industrial toxins, agricultural runoff, wastewater discharges, sewer overflows, landfills, algal blooms and microbiota. Emerging micropollutants (EMs) encompass a broad spectrum of compounds, including pharmaceutically active chemicals, personal care products, pesticides, industrial chemicals, steroid hormones, toxic nanomaterials, microplastics, heavy metals, and microorganisms. The pervasive and enduring nature of EMs has resulted in a detrimental impact on global urban water systems. Of late, these contaminants are receiving more attention due to their inherent potential to generate environmental toxicity and adverse health effects on humans and aquatic life. Although little progress has been made in discovering removal methodologies for EMs, a basic categorization procedure is required to identify and restrict the EMs to tackle the problem of these emerging contaminants. The present review paper provides a crude classification of EMs and their associated negative impact on aquatic life. Furthermore, it delves into various nanotechnology-based approaches as effective solutions to address the challenge of removing EMs from water, thereby ensuring potable drinking water. To conclude, this review paper addresses the challenges associated with the commercialization of nanomaterial, such as toxicity, high cost, inadequate government policies, and incompatibility with the present water purification system and recommends crucial directions for further research that should be pursued., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Biochar, a promising carbon-rich and carbon-negative material, can control water pollution, harness the synergy of sustainable development goals, and achieve circular economy. This study examined the performance feasibility of treating fluoride-contaminated surface and groundwater using raw and modified biochar synthesized from agricultural waste rice husk as problem-fixing renewable carbon-neutral material. Physicochemical characterizations of raw/modified biochars were investigated using FESEM-EDAX, FTIR, XRD, BET, CHSN, VSM, pH pzc , Zeta potential, and particle size analysis were analyzed to identify the surface morphology, functional groups, structural, and electrokinetic behavior. In fluoride (F-) cycling, performance feasibility was tested at various governing factors, contact time (0-120 min), initial F- levels (10-50 mg L -1 ), biochar dose (0.1-0.5 g L -1 ), pH (2-9), salt strengths (0-50 mM), temperatures (301-328 K), and various co-occurring ions. Results revealed that activated magnetic biochar (AMB) possessed higher adsorption capacity than raw biochar (RB) and activated biochar (AB) at pH 7. The results indicated that maximum F- removal (98.13%) was achieved using AMB at pH 7 for 10 mg L -1 . Electrostatic attraction, ion exchange, pore fillings, and surface complexation govern F- removal mechanisms. Pseudo-second-order and Freundlich were the best fit kinetic and isotherm for F- sorption, respectively. Increased biochar dose drives an increase in active sites due to F- level gradient and mass transfer between biochar-fluoride interactions, which reported maximum mass transfer for AMB than RB and AB. Fluoride adsorption using AMB could be described through chemisorption processes at room temperature (301 K), though endothermic sorption follows the physisorption process. Fluoride removal efficiency reduced, from 67.70% to 53.23%, with increased salt concentrations from 0 to 50 mM NaCl solutions, respectively, due to increased hydrodynamic diameter. Biochar was used to treat natural fluoride-contaminated surface and groundwater in real-world problem-solving measures, showed removal efficiency of 91.20% and 95.61%, respectively, for 10 mg L -1 F- contamination, and has been performed multiple times after systematic adsorption-desorption experiments. Lastly, techno-economic analysis was analyzed for biochar synthesis and F- treatment performance costs. Overall, our results revealed worth output and concluded with recommendations for future research on F- adsorption using biochar., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Despite of our growing understanding of microplastic's implications, research on the effects of fibrous microplastic (FMPs) on the environment is still in its infancy. Some scientists have hypothesized the possibility of natural textile fibres, which may act as one of the emerging environmental pollutants prevalent among microplastic pollutants in the environment. Therefore, this review aims to critically evaluate the toxic effects of emerging FMPs, the presence, and sources of FMPs in the environment, identification and analytical techniques, and the potential impact or toxicity of the FMPs on the environment and human health. About175 publications (2011-2023) based on FMPs were identified and critically reviewed for transportation, analysis and ecotoxicological behaviours of FMPs in the environment. Textile industries, wastewater treatment plants, and household washing of clothes are significant sources of FMPs. In addition, various characterization techniques (e.g., FTIR, SEM, RAMAN, TGA, microscope, and X-Ray Fluorescence Spectroscopy) commonly used for the identification and analysis of FMPs are also discussed, which justifies the novelty aspects of this review. FMPs are pollutants of emerging concern due to their prevalence and persistence in the environment. FMPs are also found in the food chain, which is an alarming situation for living organisms, including effects on the nervous system, digestive system, circulatory system, and genetic alteration. This review will provide readers with a comparison of different analytical techniques, which will be helpful for researchers to select the appropriate analytical techniques for their study and enhance their knowledge about the harmful effects of FMPs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A structure-activity relationship study was performed for a set of rigidified platinum-acridine anticancer agents containing linkers derived from chiral pyrrolidine and piperidine scaffolds. Screening a library of microscale reactions and selected resynthesized compounds in non-small-cell lung cancer (NSCLC) cells showed that cytotoxicities varied by more than three orders of magnitude. A potent hit compound was discovered containing a (R)-N-(piperidin-3-yl) linker (P2-6R), which killed NCI-H460 and A549 lung cancer cells 100 times more effectively than the S enantiomer (P2-6S). P2-6R accumulated in A549 cells significantly faster and produced 50-fold higher DNA adduct levels than P2-6S. Ligand similarity analysis suggests that only module 6R may be compatible with strainless monofunctional intercalative binding. NCI-60 screening and COMPARE analysis highlights the spectrum of activity and potential utility of P2-6R for treating NSCLC and other solid tumors., (© 2020 Wiley-VCH GmbH.)

Serotonergic (5-HT) and noradrenergic (NA) input to spinal motoneurons is essential for generating plateau potentials and self-sustained discharges. Extensor motoneurons are densely innervated by 5-HT and NA synapses and have robust plateau potentials and self-sustained discharges. Conversely, plateau potentials and self-sustained discharges are very rare in flexor motoneurons. The most likely reasons for this difference are that flexor motoneurons have few 5-HT and NA synapses and/or they are distributed distant to the channels responsible for plateau potentials and self-sustained discharges. However, the distribution of 5-HT and NA synapses on flexor motoneurons is unknown. Here we describe the distribution and density of 5-HT and NA synapses on motoneurons that innervate the flexor neck muscle, rectus capitis anterior (RCA), in the adult cat. Using a combination of intracellular staining, fluorescent immunohistochemistry, and 3D reconstruction techniques, we found that 5-HT and NA synapses are widely distributed throughout the dendritic trees of RCA motoneurons, albeit with a strong bias to small-diameter dendrites and to medial dendrites in the case of NA contacts. The number of 5-HT and NA contacts per motoneuron ranged, respectively, from 381 to 1,430 and from 642 to 1,382, which is 2.3- and 1.4-fold less than neck extensor motoneurons (Montague et al., J Comp Neurol 2013;521:638-656). These results suggest that 5-HT and NA synapses on flexor motoneurons may provide a powerful means of amplifying synaptic currents without incurring plateau potentials or self-sustained discharges. This feature is well suited to meet the biomechanical demands imposed on flexor muscles during different motor tasks., (© 2015 Wiley Periodicals, Inc.)

Background: Isolating specific cellular and tissue compartments from 3D image stacks for quantitative distribution analysis is crucial for understanding cellular and tissue physiology under normal and pathological conditions. Current approaches are limited because they are designed to map the distributions of synapses onto the dendrites of stained neurons and/or require specific proprietary software packages for their implementation., New Method: To overcome these obstacles, we developed algorithms to Grow and Shrink Volumes of Interest (GSVI) to isolate specific cellular and tissue compartments from 3D image stacks for quantitative analysis and incorporated these algorithms into a user-friendly computer program that is open source and downloadable at no cost., Results: The GSVI algorithm was used to isolate perivascular regions in the cortex of live animals and cell membrane regions of stained spinal motoneurons in histological sections. We tracked the real-time, intravital biodistribution of injected fluorophores with sub-cellular resolution from the vascular lumen to the perivascular and parenchymal space following a vascular microlesion, and mapped the precise distributions of membrane-associated KCC2 and gephyrin immunolabeling in dendritic and somatic regions of spinal motoneurons., Comparison With Existing Methods: Compared to existing approaches, the GSVI approach is specifically designed for isolating perivascular regions and membrane-associated regions for quantitative analysis, is user-friendly, and free., Conclusions: The GSVI algorithm is useful to quantify regional differences of stained biomarkers (e.g., cell membrane-associated channels) in relation to cell functions, and the effects of therapeutic strategies on the redistributions of biomolecules, drugs, and cells in diseased or injured tissues., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The input-output properties of motoneurons are dynamically regulated. This regulation depends, in part, on the relative location of excitatory and inhibitory synapses, voltage-dependent and -independent channels, and neuromodulatory synapses on the dendritic tree. The goal of the present study was to quantify the number and distribution of synapses from two powerful neuromodulatory systems that originate from noradrenergic (NA) and serotonergic (5-HT) neurons. Here we show that the dendritic trees of motoneurons innervating a dorsal neck extensor muscle, splenius, in the adult cat are densely, but not uniformly innervated by both NA and 5-HT boutons. Identified splenius motoneurons were intracellularly stained with Neurobiotin. Using 3D reconstruction techniques we mapped the distributions of contacts formed by NA and 5-HT boutons on the reconstructed dendritic trees of these motoneurons. Splenius motoneurons received an average of 1,230 NA contacts (range = 647-1,507) and 1,582 5-HT contacts (range = 1,234-2,143). The densities of these contacts were 10 (NA) to 6 (5-HT)-fold higher on small compared to large-diameter dendrites. This relationship largely accounts for the bias of NA and 5-HT contacts on distal dendrites and is partially responsible for the higher density of NA contacts on dendrites located more than 200 μm dorsal to the soma. These results suggest that the neuromodulatory actions of NA and 5-HT are compartmentalized and regulate the input-output properties of motoneurons according to precisely arranged interactions with voltage-dependent and -independent channels that are primarily located on small-diameter dendrites., (Copyright © 2012 Wiley Periodicals, Inc.)

We recently reported that some, but not all, axotomized propriospinal commissural interneurons (PCI) of the adult mammal can regenerate through spinal midsagittal transection injury sites (Fenrich and Rose [2009] J Neurosci 29:12145-12158). In this model, regenerating axons grow through a lesion site surrounded by a dense deposition of chondroitin sulfate proteoglycans (CSPG), which are typically inhibitory to regenerating axons. However, the mechanisms that lead some regenerating axons to grow through spinal cord injury (SCI) sites while others remain trapped in the CSPG zones or retract to their soma remain unknown. As a first step toward elucidating these mechanisms, here we show that the ability of PCI axons to regenerate across a SCI site depends on the branching patterns of their distal terminals. Using 3D reconstruction techniques through multiple serial sections and immunohistochemical analyses, we found that at 7 days postinjury a majority of PCI axons terminated in CSPG zones ipsilateral of the spinal midline. Conversely, at 9 days postinjury some PCI axons had regenerated across the midline, but others terminated outside the CSPG zones near their soma. Furthermore, we show that the most successful regenerators were those with the most extensive branching patterns, whereas those that terminated outside the CSPG zones had terminal regions indistinguishable from dystrophic terminals. Our results demonstrate that the morphological characteristics of regenerating axons play an important role in their ability to regenerate across SCI sites, and that the branching patterns of some regenerating axons are more extensive and have a far greater complexity than previously reported., (Copyright © 2011 Wiley-Liss, Inc.)

Axotomy can trigger profound alterations in the neuronal polarity of adult neurons in vivo. This can manifest itself in the development of new axon-like processes emanating from the tips of distal dendrites. Previously, these processes have been defined as axonal based on their axonal morphology. This study extends this definition to determine whether, more importantly, these processes possess the prerequisite molecular machinery to function as axons. Using a combination of intracellular labeling and immunohistochemistry, we demonstrate that the distribution of voltage-gated sodium channels on these processes matches the arrangement of these channels that is necessary for the initiation and conduction of action potentials. At terminal bouton-like structures they possess key proteins necessary for the release of synaptic vesicles (SV2 and synaptophysin). Thus, axon-like processes emanating from the tips of distal dendrites represent a rearrangement of neuronal polarity whereby axotomized neurons can develop additional functional axons in vivo.

Excitatory and inhibitory synapses may control neuronal output through a push-pull mechanism--that is, increases in excitation are coupled to simultaneous decreases in inhibition or vice versa. This pattern of activity is characteristic of excitatory and inhibitory vestibulospinal axons that mediate vestibulocollic reflexes. Previously, we showed that medial vestibulospinal tract (MVST) neurons in the rostral descending vestibular nucleus (DVN), an excitatory pathway, primarily innervate the medial dendrites of contralateral splenius motoneurons. In the present study, we tested the hypothesis that the counterparts of the push-pull mechanism, the ipsilateral inhibitory MVST synapses, are distributed on the dendritic tree such that the interactions with excitatory MVST synapses are enhanced. We combined anterograde tracing and intracellular staining in adult felines and show that most contacts (approximately 70%) between inhibitory MVST neurons in the rostral DVN and ipsilateral splenius motoneurons are also located on medial dendrites. There was a weak bias towards proximal dendrites. Using computational methods, we further show that the organization of excitatory and inhibitory MVST synapses on splenius motoneurons increases their likelihood for interaction. We found that if either excitatory or inhibitory MVST synapses were uniformly distributed throughout the dendritic tree, the proportion of inhibitory contacts in close proximity to excitatory contacts decreased. Thus, the compartmentalized distribution of excitatory and inhibitory MVST synapses on splenius motoneurons may be specifically designed to enhance their interactions during vestibulocollic reflexes. This suggests that the push-pull modulation of motoneuron output is based, in part, on the spatial arrangement of synapses on the dendritic tree., (2010. Published by Elsevier B.V. All rights reserved.)

It is well established that long, descending axons of the adult mammalian spinal cord do not regenerate after a spinal cord injury (SCI). These axons do not regenerate because they do not mount an adequate regenerative response and growth is inhibited at the injury site by growth cone collapsing molecules, such as chondroitin sulfate proteoglycans (CSPGs). However, whether axons of axotomized spinal interneurons regenerate through the inhibitory environment of an SCI site remains unknown. Here, we show that cut axons from adult mammalian spinal interneurons can regenerate through an SCI site and form new synaptic connections in vivo. Using morphological and immunohistochemical analyses, we found that after a midsagittal transection of the adult feline spinal cord, axons of propriospinal commissural interneurons can grow across the lesion despite a close proximity of their growth cones to CSPGs. Furthermore, using immunohistochemical and electrophysiological analyses, we found that the regenerated axons conduct action potentials and form functional synaptic connections with motoneurons, thus providing new circuits that cross the transected commissures. Our results show that interneurons of the adult mammalian spinal cord are capable of spontaneous regeneration after injury and suggest that elucidating the mechanisms that allow these axons to regenerate may lead to useful new therapeutic strategies for restoring function after injury to the adult CNS.

The ability of inhibitory synaptic inputs to dampen the excitability of motoneurons is augmented when persistent inward currents (PICs) are activated. This amplification could be due to an increase in the driving potential of inhibitory synapses or the deactivation of the channels underlying PICs. Our goal was to determine which mechanism leads to the amplification of inhibitory inputs by PICs. To reach this goal, we measured inhibitory postsynaptic currents (IPSCs) in decerebrate cats during somatic voltage-clamp steps. These IPSCs were generated by tonic activation of Renshaw cells. The IPSCs exhibited a rapid rise and a slower decay to a plateau level. Activation of PICs always led to an increase in the peak of the IPSC, but the amount of decay after the peak of the IPSC was inversely related to the size of the IPSC. These results were replicated in simulations based on compartmental models of motoneurons incorporating distributions of Renshaw cell synapses based on anatomical observations, and L-type calcium channels distributed as 100-microm-long hot spots centered 100 to 400 microm away from the soma. For smaller IPSCs, amplification by PICs was due to an increase in the driving force of the inhibitory synaptic current. For larger IPSCs, amplification was caused by deactivation of the channels underlying PICs leading to a lesser decay of the IPSCs. As a result of this change in the time course of the IPSC, deactivation of the channels underlying PICs leads to a greater amplification of the total inhibitory synaptic current.

In some motoneurons, L-type Ca2+ channels that partly mediate persistent inward currents (PICs) have been estimated to be arranged in 50- to 200-microm-long discrete regions in the dendrites, centered 100 to 400 microm from the soma. As a consequence of this nonuniform distribution, the interaction between synaptic inputs to motoneurons and these channels may vary according to the distribution of the synapses. For instance, >93% of synapses from Renshaw cells have been observed to be located 65 to 470 microm away from the cell body of motoneurons. Our goal was to assess whether Renshaw cell synapses are distributed in a position to more effectively control the activation of the L-type Ca2+ channels. Using compartmental models of motoneurons with L-type Ca2+ channels distributed in 100-microm-long hot spots centered 100 to 400 microm away from the soma, we compared the inhibition generated by four distributions of inhibitory synapses: proximal, distal, uniform, and one based on the location of Renshaw cell synapses on motoneurons. Regardless of whether the synapses were activated tonically or transiently, in the presence of L-type Ca2+ channels, inhibitory synapses distributed according to the Renshaw cell synapse distribution generate the largest inhibitory currents. The effectiveness of a particular distribution of inhibitory synapses in the presence of PICs depends on their ability to deactivate the channels underlying PICs, which is influenced not only by the superposition between synapses and channels, but also by the distance away from the somatic voltage clamp.

The distribution and geometry of the dendritic trees of spinal motoneurons obey several well-established rules. Some of these rules are based on systematic relationships between quantitative geometrical features (e.g. total dendritic length) and the three-dimensional trajectory followed by dendrites from their origin to their termination. Since dendritic geometry partially determines the transmission of current and voltage signals generated by synapses on the dendritic tree, our goal was to compare the efficacy of signal transmission by dendritic trajectories that followed different directions. To achieve this goal, we constructed detailed compartmental models of the dendritic trees of intracellularly stained neck motoneurons and calculated the electrotonic properties of each soma-to-terminal trajectory. These properties displayed a high degree of variability. To determine if this variability was due, in part, to the orientation (e.g. rostral, rostral-dorsal-lateral) of the trajectory, each trajectory was classified according to its orientation. The attenuation of current and voltage signals en route to the soma were strongly related to trajectory orientation. Trajectories with similar attenuation factors formed functional subunits that were arranged in distinct domains within the ventral horn. The difference in the efficacy of signal transmission between subunits was increased by activation of neighbouring synapses due to trajectory-related differences in non-linear summation. These results indicate that the input-output properties of motoneurons depend on the direction of the path taken by dendrites from their origin at the cell body to their terminals.

Previous studies show that the activation of voltage-dependent channels is dependent on the local density of synapses in the dendritic region containing voltage-dependent channels. We hypothesized that the selective innervation of excitatory vestibulospinal (VST) neurons on the medial dendrites of contralateral splenius motoneurons is designed to enhance the activation of persistent inward currents (PICs) mediated by dendritic L-type Ca(2+) channels. Using compartmental models of splenius motoneurons we compared the synaptic current reaching the soma in response to excitatory input generated by synapses with two different distribution patterns. The medial distribution was based on the arrangement of VST synapses on the dendrites of contralateral splenius motoneurons and the uniform distribution was based on an arrangement of synapses with no particular bias to any region of the dendritic tree. The number of synapses in each distribution was designed to match estimates of the number of VST synapses activated by head movements. In the absence of PICs, the current delivered by the synapses in the uniform distribution was slightly greater. However, the maximal currents were small, < or = 4.1 nA, regardless of the distribution of synapses. In models equipped with L-type Ca(2+) channels, PIC activation was largely determined by the local density of synapses in proximity to the L-type Ca(2+) channels. In 3 of 5 cells, this led to a 2- to 4-fold increase in the current generated by synapses in the medial distribution compared to the uniform distribution. In the other two cells, the amplification bias was in favour of the medial distribution but was either small or restricted to a narrow range of frequencies. These simulations suggest that the innervation pattern of VST axons on contralateral splenius motoneurons is arranged to strengthen an otherwise weak synaptic input by increasing the likelihood of activating PICs. Additional simulations suggest that this prediction can be tested using common experimental protocols.

Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein, microtubule-associated protein2a/b (MAP2a/b); some had GAP-43-immunoreactive terminals; and nearly all had morphological features typical of axons. Dendrites of other CINs did not give rise to de novo axons. These CINs did, however, each have a long axon-like process (L-ALP) that projected directly from the soma or a very proximal dendrite. L-ALPs were devoid of MAP2a/b immunoreactivity. Some of these L-ALPs projected through the lesion and formed bouton-like swellings. These results suggest that proximally axotomized spinal interneurons have the potential to form new connections via de novo axons that emerge from distal dendrites. Others may be capable of regeneration of their original axon., ((c) 2007 Wiley-Liss, Inc.)

In the presence of monoamines, L-type Ca(2+) channels on the dendrites of motoneurons contribute to persistent inward currents (PICs) that can amplify synaptic inputs two- to sixfold. However, the exact location of the L-type Ca(2+) channels is controversial, and the importance of the location as a means of regulating the input-output properties of motoneurons is unknown. In this study, we used a computational strategy developed previously to estimate the dendritic location of the L-type Ca(2+) channels and test the hypothesis that the location of L-type Ca(2+) channels varies as a function of motoneuron size. Compartmental models were constructed based on dendritic trees of five motoneurons that ranged in size from small to large. These models were constrained by known differences in PIC activation reported for low- and high-conductance motoneurons and the relationship between somatic PIC threshold and the presence or absence of tonic excitatory or inhibitory synaptic activity. Our simulations suggest that L-type Ca(2+) channels are concentrated in hotspots whose distance from the soma increases with the size of the dendritic tree. Moving the hotspots away from these sites (e.g., using the hotspot locations from large motoneurons on intermediate-sized motoneurons) fails to replicate the shifts in PIC threshold that occur experimentally during tonic excitatory or inhibitory synaptic activity. In models equipped with a size-dependent distribution of L-type Ca(2+) channels, the amplification of synaptic current by PICs depends on motoneuron size and the location of the synaptic input on the dendritic tree.

In the presence of neuromodulators such as serotonin and noradrenaline, motoneurons exhibit persistent inward currents (PICs) that serve to amplify synaptic inputs. A major component of these PICs is mediated by L-type Ca(2+) channels. Estimates based on electrophysiological studies indicate that these channels are located on the dendrites, but immunohistochemical studies of their precise distribution have yielded different results. Our goal was to determine the distribution of these channels using computational methods. A theoretical analysis of the activation of PICs by a somatic current injection in the absence or presence of synaptic activity suggests that L-type Ca(2+) channels may be segregated to discrete hot spots 25-200 microm long and centered 100-400 microm from the soma in the dendritic tree. Compartmental models based on detailed anatomical measurements of the structure of feline neck motoneurons with L-type Ca(2+) channels incorporated in these regions produced plateau potentials resulting from PIC activation. Furthermore, we replicated the experimental observation that the somatic threshold at which PICs were activated was depolarized by tonic activation of inhibitory synapses and hyperpolarized by tonic activation of excitatory synapses. Models with L-type Ca(2+) channels distributed uniformly were unable to replicate the change in somatic threshold of PIC activation. Therefore we conclude that the set of L-type Ca(2+) channels mediating plateau potentials is restricted to discrete regions in the dendritic tree. Furthermore, this distribution leads to the compartmentalization of the dendritic tree of motoneurons into subunits whose sequential activation lead to the graded amplification of synaptic inputs.

A single spinal motoneuron receives tens of thousands of synapses. The neurotransmitters released by many of these synapses act on iontotropic receptors and alter the driving potential of neighboring synapses. This interaction introduces an intrinsic nonlinearity in motoneuron input-output properties where the response to two simultaneous inputs is less than the linear sum of the responses to each input alone. Our goal was to determine the impact of this nonlinearity on the current delivered to the soma during activation of predetermined numbers and distributions of excitatory and inhibitory synapses. To accomplish this goal we constructed compartmental models constrained by detailed measurements of the geometry of the dendritic trees of three feline motoneurons. The current "lost" as a result of local changes in driving potential was substantial and resulted in a highly nonlinear relationship between the number of active synapses and the current reaching the soma. Background synaptic activity consisting of a balanced activation of excitatory and inhibitory synapses further decreased the current delivered to the soma, but reduced the nonlinearity with respect to the total number of active excitatory synapses. Unexpectedly, simulations that mimicked experimental measures of nonlinear summation, activation of two sets of excitatory synapses, resulted in nearly linear summation. This result suggests that nonlinear summation can be difficult to detect, despite the substantial "loss" of current arising from nonlinear summation. The magnitude of this "loss" appears to limit motoneuron activity, based solely on activation of iontotropic receptors, to levels that are inadequate to generate functionally meaningful muscle forces.

Current descriptions of the organization of synapses on the dendritic trees of spinal motoneurons indicate that the inputs are arranged in several patterns: some are widely distributed; some are distributed to proximal dendrites; others are distributed based on the trajectory of the dendrites. However, the principles governing the organization of synapses on spinal motoneurons remain poorly defined. Our goal was to extend the descriptions of the distribution of synapses, identified by their source, on the dendritic trees of spinal motoneurons. We combined anterograde and intracellular staining techniques in cats to determine the distribution of contacts between excitatory axons from the rostral aspect of the descending vestibular nucleus and the dendrites of motoneurons supplying a dorsal neck muscle, splenius. In five of five motoneurons, the contacts were preferentially distributed on dendrites medial to the soma. This qualitative observation was confirmed by using Monte Carlo methods. The results from this analysis showed that the distribution of contacts can be explained not by the overall distribution of the dendritic membrane area but rather by a systematic innervation of the medial regions of the dendritic trees (P < 0.02). Despite this selectivity, there was no additional bias in the distribution of contacts to proximal vs. distal dendrites. By concentrating excitatory synapses in a restricted region of the dendritic tree, the actions of vestibulospinal connections on neck motoneurons may be increased as a result of a greater probability of activating persistent inward currents on the dendrites., (2005 Wiley-Liss, Inc.)

Inhibitory synaptic inputs to Renshaw cells are concentrated on the soma and the juxtasomatic dendrites. In the present study, we investigated whether this proximal bias leads to more effective inhibition under different neuronal operating conditions. Using compartmental models based on detailed anatomical measurements of intracellularly stained Renshaw cells, we compared the inhibition produced by glycine/gamma-aminobutyric acid-A (GABA(A)) synapses when distributed with a proximal bias to the inhibition produced when the same synapses were distributed uniformly (i.e., with no regional bias). The comparison was conducted in subthreshold and suprathreshold conditions. The latter were mimicked by voltage clamping the soma to -55 mV. The voltage clamp reduces nonlinear interactions between excitatory and inhibitory synapses. We hypothesized that for electrotonically compact cells such as Renshaw cells, the strength of the inhibition would become much less dependent on synaptic location in suprathreshold conditions. This hypothesis was not confirmed. The inhibition produced when inhibitory inputs were proximally distributed was always stronger than when the same inputs were uniformly distributed. In fact, the relative effectiveness of proximally distributed inhibitory inputs over uniformly distributed synapses was greater in suprathreshold conditions than that in subthreshold conditions. The somatic voltage clamp minimized saturation of inhibitory driving potentials. Because this effect was greatest near the soma, the current produced by more distal synapses suffered a greater loss because of saturation. Conversely, in subthreshold conditions, the effectiveness of proximal synapses was substantially reduced at high levels of background synaptic activity because of saturation. Our results suggest glycine/GABA(A) synapses on Renshaw cells are strategically distributed to block the powerful excitatory drive produced by recurrent collaterals from motoneurons.

The distribution and geometry of the dendritic trees of spinal motoneurons obey several well-established rules. Some of these rules are based on systematic relationships between quantitative geometrical features (e.g., total dendritic length) and the three-dimensional trajectory followed by dendrites from their origin to their termination. Because dendritic geometry partially determines the transmission of current and voltage signals generated by synapses on the dendritic tree, our goal was to compare the efficacy of signal transmission by dendritic trajectories that followed different directions. To achieve this goal, we constructed detailed compartmental models of the dendritic trees of three intracellularly stained biventer cervicis/complexus (BCCM) motoneurons and calculated the electronic properties of 361 dendritic paths. Each trajectory was classified according to its orientation, e.g., rostral, rostral-dorsal-lateral. The attenuation of current and voltage signals en route to the soma was strongly related to trajectory orientation. Trajectories with similar attenuation factors formed functional subunits that were arranged in distinct domains within the ventral horn. Changes in R(m) or R(i) had little effect on which trajectories belonged to each functional subunit. However, differences in the efficacy of signal transmission between subunits increased during high network activity (mimicked by decreases in R(m)). The most efficient subunit delivered two times more current and four times more voltage to the soma than the least efficient subunit. These results indicate that the input-output properties of motoneurons depend on the direction of the path taken by dendrites from their origin at the cell body to their terminals., (Copyright 2004 Wiley-Liss, Inc.)

At 8-12 weeks post axotomy, unusual distal processes (UDPs) with axon-like structural (uniform diameter, tortuous) and molecular (growth-associated protein [GAP]43, absence of microtubule-associated protein [MAP]2a/b immunoreactivity) features emerge from distal motoneuron dendrites (Rose et al. [2001] Eur J Neurosci 13:1166-1176). In this study, we determine the time course of molecular and morphological changes associated with the formation of axons from dendrites. Motoneurons innervating neck muscles in the adult cat were permanently axotomized for 2, 4, 20, or 35 weeks and intracellularly stained with Neurobiotin. Computer-assisted reconstructions were used to map the location of MAP2a/b and GAP-43 immunoreactivity. At 2 and 4 weeks post axotomy, all UDPs had short appendages, giving them an arboreal appearance. They were immunoreactive for GAP-43 and lacked immunostaining for MAP2a/b. Axon-like UDPs were not seen until 8-12 weeks post axotomy. By 20 and 35 weeks post axotomy, some axon-like UDPs acquired morphological features of axons with synaptic connections (right-angled branching, bouton-like specializations). GAP-43 immunoreactivity was not detected in any axotomized motoneurons by 20 weeks post axotomy, whereas all UDPs remained devoid of MAP2a/b immunoreactivity even at 35 weeks post axotomy. These molecular changes accompanied structural modifications to proximal regions of "dendrites" giving rise to UDPs. The distance from the ends of the UDPs to the soma did not change. Thus, all UDPs begin as simple, arboreal structures with molecular features of growing axons, but over a period of 35 weeks, some UDPs slowly acquire morphological and molecular features of motoneuron axons with synaptic connections. These results suggest a new modus operandi for axonal growth and the establishment of new synaptic connections after injury., (Copyright 2003 Wiley-Liss, Inc.)

The morphological and electrotonic properties of 4 motoneurons, 8 Ia inhibitory interneurons, and 4 Renshaw cells were compared. The morphological analysis, based on 3-D reconstructions of the cells, revealed that dendrites of motoneurons are longer and more extensively branched. Renshaw cells have dendrites that are shorter and simpler in structure. Dendrites of Ia inhibitory interneurons could be as long as those of motoneurons but the branching structure resembled that of Renshaw cells. Compartmental models were used to determine the electrotonic properties of the paths from each dendritic terminal to the soma. The attenuations of steady-state voltage changes in motoneurons were 3 and 7 times larger than in Ia inhibitory interneurons and Renshaw cells, respectively. The same relative order was observed for current attenuation and electrotonic length. The dendritic input resistances in Renshaw cells were 2 and 4 times larger than in Ia inhibitory interneurons and motoneurons, respectively. The difference in these electrotonic properties increased during higher synaptic activity as modeled by a decrease of Rm. The peak amplitudes of voltage transients at sites of brief, synaptic-like changes in conductance were highly dependent on cell class and were largest in Renshaw cells and smallest in motoneurons. In combination with class-specific differences in the attenuation of transient voltage signals, this led to large differences in the peak amplitudes of somatic voltage transients. Differences in the rise times and half-widths of the voltage transients were observed as well. Thus, based on passive properties, each cell class has a unique set of input/output properties.

Following axotomy, morphologically unusual, distal processes (UDPs) emerge from motoneuron dendrites. These processes contain an axonal protein, growth-associated protein 43 (GAP-43) but lack immunostaining for the dendritic protein microtubule-associated protein 2a/b (MAP2a/b). Thus, it appears that neuronal polarity alters following axotomy. Our goal was to describe this change in neuronal polarity on a more detailed and quantitative level. We asked two questions: Following axotomy, where in the entire neuron does the immunoreactivity for MAP2a/b and GAP-43 change and do these changes reflect a transformation of dendrite to axon or growth from terminal dendrites? Using intracellular labeling and immunocytochemistry, changes in MAP2a/b and GAP-43 immunoreactivity were also found in processes with a morphology typical of terminal branches of intact motoneurons (called simple distal processes [SDPs]), as well as UDPs. Trajectories (the path from the soma to a single terminus) with UDPs and SDPs were longer than trajectories without these processes, and trajectories with UDPs were the longest. Trajectories without UDPs or SDPs were similar in length to trajectories from intact motoneurons. The distance from the soma to the point where MAP2a/b immunoreactivity became absent in trajectories with UDPs or SDPs was similar to the length of trajectories from intact motoneurons. Thus, following axotomy, two morphologically distinct types of axon-like processes emerge from dendrites. The formation of these processes does not involve a transformation of the original dendrite, but rather growth at the ends of dendrites., (Copyright 2002 Wiley-Liss, Inc.)

Mesencephalic neurons projecting to the upper cervical spinal cord were examined by mapping the distributions of labeled cells after injecting fluorescent tracers or wheat-germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) into the C1 segment. Injections into the central or deep regions of the ventral horn produced retrograde labeling in cells of several mesencephalic regions. The majority of cells were found contralaterally in the superior colliculus and red nucleus, and ipsilaterally in and around the interstitial nucleus of Cajal (INC), in the cuneiform region, and in the fields of Forel. Smaller numbers of cells were located in the periaqueductal gray matter, nucleus annularis, and magnocellular nucleus of the posterior commissure. Dorsomedial injections in the ventral horn near the ventral commissure labeled only a subset of these projections, including cells in the mesencephalic reticular formation adjacent to the INC and in the nucleus annularis. Dorsolateral injections labeled some cells in the superior colliculus and were particularly effective at labeling cells in the red nucleus. These results suggest that at least ten different cell groups project to the ventral horn of the first cervical segment. Most, but not all, groups originate from regions implicated previously in the control of eye or head movements.

The distinctive features of axons and dendrites divide most neurons into two compartments. This polarity is fundamental to the ability of most neurons to integrate synaptic signals and transmit action potentials. It is not known, however, if the polarity of neurons in the adult mammalian nervous system is fixed or plastic. Following axotomy, some distal dendrites of neck motoneurons in the adult cat give rise to unusual processes that, at a light microscopic level, resemble axons (Rose, P.K. & Odlozinski, M., J. Comp. Neurol., 1998, 390, 392). The goal of the present experiments was to characterize these unusual processes using well-established ultrastructural and molecular criteria that differentiate dendrites and axons. These processes were immunoreactive for growth-associated protein-43 (GAP-43), a protein that is normally confined to axons. In contrast, immunoreactivity for a protein that is widely used as a marker for dendrites, microtubule-associated protein (MAP)-2a/b, could not be detected in the unusual distal arborizations. At the electron microscopic level, unusual distal processes contained dense collections of neurofilaments and were frequently myelinated. These molecular and structural characteristics are typical of axons and suggest that the polarity of adult neurons in the mammalian nervous system can be disrupted by axotomy. If this transformation in neuronal polarity is common to other types of neurons, axon-like processes emerging from distal dendrites may represent a mechanism for replacing connections lost due to injury. Alternatively, the connections formed by these axons may be aberrant and therefore maladaptive.

Vestibulospinal axon collaterals in C1 and C2 were stained following injections of Phaseolus vulgaris leucoagglutinin (PHA-L) into the lateral vestibular nucleus (LVN). The distribution and geometry of collaterals within three regions of the ventral horn were determined at the light microscopic level. These processes were subsequently examined at the electron microscopic level to define the relationship between their ultrastructural characteristics and their geometry and location. All round or elliptical varicosities, whose diameters exceeded the diameter of the adjacent axon shaft by a factor of two, as measured at the light microscopic level, contained synaptic vesicles and contacted dendrites or somata. These varicosities accounted for 82% of labelled axon terminals found at the electron microscopic level. Thus, axon terminals stained with PHA-L can be identified reliably at the light microscopic level, but synaptic density will be slightly underestimated. One-hundred and thirty-eight axon terminals were classified as excitatory or inhibitory on the basis of well-established morphological criteria (e.g., vesicle shape). Placed in the context of previous physiological observations describing the excitatory or inhibitory actions of medial and lateral vestibulospinal tract (MVST and LVST) neurons, our results suggest that projections from the LVN to the ipsilateral ventral horn originate primarily from the LVST. These connections are excitatory. Ipsilateral connections via the MVST are inhibitory and are largely confined to a region near the border of laminae VII and VIII. Most axon terminals in the contralateral ventral horn were inhibitory. This result indicates that the LVN is the source of a specific subset of crossed MVST axons with inputs from the posterior semicircular canal., (Copyright 1999 Wiley-Liss, Inc.)

Our goal was to study potential substrates for cortical modulation of vestibular reflexes in the cat. In initial experiments, injections of wheat-germ-agglutinate-horseradish-peroxidase into Deiters' nucleus and the rostral descending nucleus revealed bilateral colonies of retrogradely filled neurons in cortical areas 6, 2, and 3a (about 60 cells per colony). In cats anesthetized with chloralose-urethane, we stimulated areas 2 and 3a with trains of pulses while recording from ipsilateral vestibular-nucleus neurons, which were characterized by their responses to sinusoidal tilts and tested for the presence of antidromic responses to stimulation of the upper cervical cord. A majority of the neurons was affected by cortical stimulation, showing either facilitation, inhibition, or a mixture of the two. Stimulation in area 2 was more effective than stimulation in area 3a. Despite the anatomic presence of direct cortico-vestibular projections, properties of facilitation and inhibition suggest that both were evoked by polysynaptic pathways. Cortical effects were broadly distributed to vestibular neurons without regard to responses of these neurons to sinusoidal tilts. There was no significant difference between effects on lateral and medial vestibulospinal tract neurons, but, as a group, vestibulospinal neurons were much more likely to be affected by cortical stimulation than neurons not antidromically activated from the C2 segment. We conclude that, by their influence on vestibulospinal neurons, neurons in cortical areas 2 and 3a should be able to modulate, in behaving animals, vestibular reflexes acting on the neck and limbs.

The morphologic characteristics of neck motoneurons with intact axons were compared with those of neck motoneurons that had been permanently axotomized for 11 to 17 weeks. Motoneurons were identified antidromically, intracellularly stained with horseradish peroxidase (HRP) and examined after reconstructions of their entire dendritic tree. Axotomized motoneurons differed qualitatively and quantitatively from motoneurons with intact axons. The distal branches of axotomized motoneurons exhibited two novel features: some gave rise to tangled appendages that exhibited growth cone-like specializations resembling lamellipodia and filopodia; others followed a meandering path and had unusually large diameters. These branches showed a discontinuous pattern of staining that was similar to the appearance of myelinated axons stained intra-axonally with HRP. A quantitative analysis of the dendritic trees of 13 completely reconstructed dendritic trees (five axotomized motoneurons and eight motoneurons with intact axons) showed that total dendritic surface area, total dendritic length, and total number of branches increased 38, 34, and 215%, respectively, after axotomy. These measurements were confirmed by comparing the sizes of a larger number of motoneurons (16 axotomized and 21 intact), calculated on the basis of correlations between dendritic tree size and proximal dendritic diameter. We conclude, therefore, that neck motoneurons, in contrast to other types of motoneurons, expand their dendritic trees after axotomy. It is suggested that this expansion is a consequence of two mechanisms: one involves dendritic growth, possibly leading to new synaptic connections; the other causes a conversion of some dendrites into axons.

The specific membrane resistivity of motoneurons at or near the soma (Rms) is much lower than the specific membrane resistivity of the dendritic tree (Rmd). The goal of the present experiments was to investigate the contribution of tonically active voltage-dependent potassium channels at or near the soma to the low Rms. These channels were blocked with the use of intracellular injections of cesium. Input resistance (RN), Rms/Rmd, a conductance representing voltage-dependent potassium channels on the soma, GK, and a conductance attributed to damage caused by electrode impalement, GDa, were estimated from voltage responses to a step of current. The effect of intracellular injections of cesium on electrotonic structure was determined with the use of two strategies: 1) a population analysis that compared data from two groups of motoneurons, those recorded with potassium acetate electrodes (control group) and those recorded with cesium acetate electrodes after the motoneurons were loaded with cesium; and 2) an analysis of changes in electrotonic structure that occurred over the course of multiple injections of cesium or during similar periods of time in control cells. RN of control and cesium-loaded motoneurons was similar. Over the course of the recordings, RN of control cells usually increased and this increase was associated with a hyperpolarization. In contrast, increases in RN after successive injections of cesium were closely linked to a depolarization. At corresponding membrane potentials, Rms/Rmd of cesium-loaded motoneurons was greater than Rms/Rmd of control motoneurons. Over the course of cesium injections, Rms/Rmd increased and the membrane potential depolarized. In contrast, increases in Rms/Rmd observed during the course of recordings from control cells were associated with a hyperpolarization. Compared with control cells at corresponding membrane potentials, GK was less in cesium-loaded cells. Increases in GK that occurred over the course of recordings in control cells were closely coupled to a depolarization. In cesium-loaded cells, GK usually decreased as the cell depolarized during the injections. In control cells, increases in GDa that occurred during the recording period were closely coupled to a depolarization. In contrast, changes in GDa that occurred during cesium injections were not related to the change in membrane potential and did not explain the corresponding changes in Rms/Rmd and membrane potential. The results of this study indicate that voltage-dependent potassium channels contribute to the somatic shunt (low Rms) in neck motoneurons and provide a voltage-dependent mechanism for the dynamic regulation of motoneuron electrotonic properties.

Some vestibulospinal pathways are composed of a homogeneous collection of axons with similar intraspinal collaterals. Other pathways contain axons whose collaterals vary in terms of shape, distribution, and complexity. The purpose of the present study was to extend the study of homogeneity versus heterogeneity of vestibulospinal axons to vestibulospinal axons that travel in the ventral funiculus ipsilateral to their cells of origin. Collaterals of these axons were stained following extracellular injections of Phaseolus vulgaris-leucoagglutinin in rostral parts of the medial and descending vestibular nuclei. All collaterals found in C2 and C3 were reconstructed. Collaterals arising from small diameter (0.5 to 2.9 microns) axons usually consisted of a single main branch with short side branches. The termination zones of most of these collaterals formed a narrow path in lamina VIII, but the location of this pathway was highly variable. Collaterals arising from large-diameter (3.0-6.1 microns) axons were usually more complex and consisted of many branches with en passant and terminal boutons that were located in motoneuron nuclei as well as laminae VIII and VII. Despite a relationship between termination zone and the position of the parent axon in the ventral funiculus, the variability in collaterals from large-diameter axons precluded a simple classification scheme. These results demonstrate that diversity, instead of homogeneity, is a characteristic feature of vestibulospinal axons that originate from the medial and descending vestibular nuclei and travel in the ipsilateral ventral funiculus. This pathway is therefore composed of multiple anatomical subunits that, as individuals, may selectively coordinate the activity of specific combinations of interneurons and motoneurons.

Stabilization of the head is required not only for adequate motor performance, such as maintaining balance while standing or walking, but also for the adequate reception of sensory inputs such as visual and auditory information. The vestibular organs, which consist of three approximately orthogonal semicircular canals (anterior, horizontal, posterior) and two otolith organs (utriculus, sacculus), provide the most important input for the detection of head movement. Activation of afferents from these receptors evokes the vestibulocollic reflex (VCR), which stabilizes head position in space. In this review, which is the outgrowth of a session of the vestibular symposium held in Hawaii in April, 1994, we discuss the neural substrate of this reflex and some aspects of the central processing involved in its production. Some topics are not considered, in particular the important interaction between the VCR and the cervicocollic reflex evoked by activation of neck afferents (70,119), and attempts to model the reflex (69).

1. The distribution of terminals from vestibulospinal (VS) axons on the dendritic trees of neck motoneurons was determined by combining the anterograde transport of Phaseolus Vulgaris Leucoagglutinin (PHA-L) with intracellular staining techniques and three-dimensional reconstruction methods. 2. Contacts between VS axon terminals and dendrites were arranged in a nonuniform pattern that depended on the orientation (i.e., rostro-caudal vs. dorsolateral) of the dendrites. 3. This innervation pattern satisfies a critical structural condition necessary for selective nonlinear interactions between pairs of simultaneously active inputs to motoneurons.